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This glossary of engineering terms is a list of definitions about the major concepts of engineering . Please see the bottom of the page for glossaries of specific fields of engineering.
When any system at equilibrium for a long period of time is subjected to a change in concentration , temperature , volume , or pressure , (1) the system changes to a new equilibrium, and (2) this change partly counteracts the applied change.
It is common to treat the principle as a more general observation of systems , [ 309 ] such as
When a settled system is disturbed, it will adjust to diminish the change that has been made to it
or, "roughly stated", [ 309 ]
Any change in status quo prompts an opposing reaction in the responding system. | https://en.wikipedia.org/wiki/Glossary_of_engineering:_A–L |
This glossary of engineering terms is a list of definitions about the major concepts of engineering . Please see the bottom of the page for glossaries of specific fields of engineering. | https://en.wikipedia.org/wiki/Glossary_of_engineering:_M–Z |
This is a glossary of environmental science .
Environmental science is the study of interactions among physical, chemical, and biological components of the environment . Environmental science provides an integrated, quantitative, and interdisciplinary approach to the study of environmental systems.
considered ideal for gardening and agricultural uses. | https://en.wikipedia.org/wiki/Glossary_of_environmental_science |
Game theory is the branch of mathematics in which games are studied: that is, models describing human behaviour. This is a glossary of some terms of the subject.
σ i {\displaystyle \sigma \ _{i}} is an element of Σ i {\displaystyle \Sigma \ ^{i}} .
σ − i {\displaystyle \sigma \ _{-i}} an element of Σ − i = ∏ j ∈ N , j ≠ i Σ j {\displaystyle \Sigma \ ^{-i}=\prod _{j\in \mathrm {N} ,j\neq i}\Sigma \ ^{j}} , is a tuple of strategies for all players other than i .
A game in normal form is a function:
Given the tuple of strategies chosen by the players, one is given an allocation of payments (given as real numbers).
A further generalization can be achieved by splitting the game into a composition of two functions:
the outcome function of the game (some authors call this function "the game form"), and:
the allocation of payoffs (or preferences ) to players, for each outcome of the game.
This is given by a tree , where at each vertex of the tree a different player has the choice of choosing an edge . The outcome set of an extensive form game is usually the set of tree leaves.
A game in which players are allowed to form coalitions (and to enforce coalitionary discipline). A cooperative game is given by stating a value for every coalition:
It is always assumed that the empty coalition gains nil. Solution concepts for cooperative games
usually assume that the players are forming the grand coalition N {\displaystyle N} , whose value ν ( N ) {\displaystyle \nu (N)} is then divided among the players to give an allocation.
A Simple game is a simplified form of a cooperative game, where the possible gain is assumed to be either '0' or '1'. A simple game is couple ( N , W ), where W is the list of "winning" coalitions , capable of gaining the loot ('1'), and N is the set of players. | https://en.wikipedia.org/wiki/Glossary_of_game_theory |
This is a glossary of some terms used in the branch of mathematics known as topology . Although there is no absolute distinction between different areas of topology, the focus here is on general topology . The following definitions are also fundamental to algebraic topology , differential topology and geometric topology . For a list of terms specific to algebraic topology, see Glossary of algebraic topology .
All spaces in this glossary are assumed to be topological spaces unless stated otherwise.
Here are some facts about submaximality as a property of topological spaces: | https://en.wikipedia.org/wiki/Glossary_of_general_topology |
This glossary of genetics and evolutionary biology is a list of definitions of terms and concepts used in the study of genetics and evolutionary biology , as well as sub-disciplines and related fields, with an emphasis on classical genetics , quantitative genetics , population biology , phylogenetics , speciation , and systematics . It has been designed as a companion to Glossary of cellular and molecular biology , which contains many overlapping and related terms; other related glossaries include Glossary of biology and Glossary of ecology .
Also called functionalism .
Also called geographic speciation , vicariance , vicariant speciation , and dichopatric speciation .
Also called an ancestral character , primitive character , or primitive trait .
Also called positive assortative mating and homogamy .
Also testcrossing .
Also simply called the Dobzhansky–Muller model .
Also called a monophyletic group .
Also convergence .
Also crossing and outbreeding .
Also Darwinian theory and Darwinian evolution .
Also derived character , advanced character , and advanced trait .
Denoted in shorthand with the somatic number 2n .
Also positive selection .
Also negative assortative mating and heterogamy .
Also diversifying selection .
Also divergence .
Also gene amplification .
Sometimes used interchangeably with genetic variation .
Also called allelic drift or the Sewall Wright effect .
Also genetic draft and the hitchhiking effect .
Also DNA testing and genetic screening .
Sometimes used interchangeably with genetic variation .
Sometimes used interchangeably with genetic diversity and genetic variability .
Denoted in shorthand with the somatic number n .
Also inheritance .
Also hybrid vigor and outbreeding enhancement .
Also homologs or homologues .
Also lateral gene transfer (LGT) .
Also incrossing .
Also introgressive hybridization .
Also called the last universal cellular ancestor or simply the last universal ancestor .
Also pedigree .
Also called lineage-branching .
Plural loci .
Also environmental genomics , ecogenomics , and community genomics .
Also point-nonsense mutation .
Also nonsynonymous substitution or replacement mutation .
Also ontogenesis and morphogenesis .
Also outcrossing or crossbreeding .
Also maximum parsimony .
Also polypheny .
Also multifurcation .
Also genetic bottleneck .
Also prosposito for a male subject and prosposita for a female subject.
Also neotype .
Also purebreed .
Also complex trait .
Also refuge .
Also called network evolution .
Also reversion .
Also Fisherian runaway .
Also selection pressure .
Denoted in shorthand with a + superscript. | https://en.wikipedia.org/wiki/Glossary_of_genetics_and_evolutionary_biology |
This glossary of industrial automation is a list of definitions of terms and illustrations related specifically to the field of industrial automation . For a more general view on electric engineering, see Glossary of electrical and electronics engineering . For terms related to engineering in general, see Glossary of engineering .
This article incorporates text from this source, which is in the public domain : IS 15571: Industrial automation glossary . New Delhi, Bureau of Indian Standards . 2005. | https://en.wikipedia.org/wiki/Glossary_of_industrial_automation |
The need for a clearly defined and consistent invasion biology terminology has been acknowledged by many sources. Invasive species , or invasive exotics , is a nomenclature term and categorization phrase used for flora and fauna, and for specific restoration-preservation processes in native habitats . Invasion biology is the study of these organisms and the processes of species invasion.
The terminology in this article contains definitions for invasion biology terms in common usage today, taken from accessible publications. References for each definition are included. Terminology relates primarily to invasion biology terms with some ecology terms included to clarify language and phrases on linked articles.
Definitions of "invasive non-indigenous species have been inconsistent", which has led to confusion both in literature and in popular publications (Williams and Meffe 2005). Also, many scientists and managers feel that there is no firm definition of non-indigenous species, native species, exotic species, "and so on, and ecologists do not use the terms consistently." (Shrader-Frechette 2001) Another question asked is whether current language is likely to promote "effective and appropriate action" towards invasive species through cohesive language (Larson 2005). Biologists today spend more time and effort on invasive species work because of the rapid spread, economic cost, and effects on ecological systems, so the importance of effective communication about invasive species is clear. (Larson 2005)
Controversy in invasion biology terms exists because of past usage and because of preferences for certain terms. Even for biologists, defining a species as native may be far from being a straightforward matter of biological classification based on the location or the discipline a biologist is working in (Helmreich 2005). Questions often arise as to what exactly makes a species native as opposed to non-native, because some non-native species have no known negative effects (Woods and Moriarty 2001). Natural biological invasions, generally considered range expansions, and introductions involving human activities are important and could be considered a normal ecological process (Vermeij 2005). Non-native and native species may be sometimes considered invasive, and these invasions often follow human-induced landscape changes, with subsequent damage to existing landscapes a value judgment (Foster and Sandberg 2004). As a result, many important terms relevant to invasion biology, such as invasive, weed, or transient, include qualities that are "open to subjective interpretation" (Colautti and MacIsaac 2004). Sometimes one species can have both beneficial and detrimental effects, such as the Mosquito fish ( Gambusia affinis ), which has been widely introduced because of its suppression of larval mosquitoes , although it also has negative impacts on native species of insects, fish and amphibians (Colautti and MacIsaac 2004).
The large number and current complexity of terms makes interpretation of some of the invasion biology literature challenging and intimidating. Exotic, alien, transplanted, introduced, non-indigenous, and invasive are all words that have been used to describe plants and animals that have been moved beyond their native ranges by humans (Williams and Meffe 2005), along with other terms such as foreign, injurious, aquatic nuisance, pest, non-native, all with a particular implication. Even the use of what seem to be simple, basic terms to articulate ecological concepts "can confuse ideological debates and undermine management efforts" (Colautti and MacIsaac 2004). Attempts to redefine commonly used terms in invasion biology have been difficult because many authors and biologists are particular to a favorite definition (Colautti and MacIsaac 2004). Also, the status and identification of any species as an invader, a weed, or an exotic are "conditioned by cultural and political circumstances." (Robbins 2004)
Where words in a sentence are also defined elsewhere in this article, they appear in italics. | https://en.wikipedia.org/wiki/Glossary_of_invasion_biology_terms |
This is a glossary of levelling terms. Levelling is a surveying method used to find relative height, one use of which is to ensure ground is level during construction, for example, when excavating to prepare for laying a foundation for a house. | https://en.wikipedia.org/wiki/Glossary_of_levelling_terms |
This glossary provides an overview of terms used in the description of lichens , composite organisms arising from algae or cyanobacteria living symbiotically among filaments of multiple fungus species. [ 1 ] [ 2 ]
Erik Acharius , known as the "father of lichenology," coined many lichen terms still in use today around the turn of the 18th century. Before that, only a couple of lichen-specific terms had been proposed. Johann Dillenius introduced scyphus in 1742 to describe the cup-shaped structures associated with genus Cladonia , while in 1794 Michel Adanson used lirella for the furrowed fruitbodies of the genus Graphis . Acharius introduced numerous terms to describe lichen structures, including apothecium , cephalodium , cyphellae , podetium , proper margin , soredium , and thallus . In 1825, Friedrich Wallroth published the first of his multi-volume work Naturgeschichte der Flechten ("Natural History of Lichens"), in which he proposed an alternative terminology based largely on roots from the Greek language . His work, presented as an alternative to that of Acharius (of whom he was critical) was not well received, and the only terms he proposed to gain widespread acceptance were epi- and hypophloeodal , hetero- and homoiomerous , and gonidium , the last of which remained in use until the 1960s. [ 3 ] Until about 1850, there were 21 terms for features of the lichen thallus that remain in use today. [ 3 ]
The increasing availability of the optical microscope as an aid to identifying and characterizing lichens led to the creation of new terms to describe structures that were previously too small to be visualized. Contributions were made by Julius von Flotow (e.g. epithecium ), Edmond Tulasne (e.g pycnidium ), and William Nylander (e.g. pseudocyphella , thecium ). Gustav Wilhelm Körber , an early proponent of using spore structure as a character in lichen taxonomy, introduced amphithecium , muriform , and "polari-dyblastae", later anglicized to "polari-bilocular" and then shortened to polarilocular . [ 4 ] In the next five decades that followed, many other additions were made to the repertoire of lichen terms, subsequent to the increased understanding of lichen anatomy and physiology made possible by microscopy. For whatever reasons, there were not any new terms (still currently used) introduced from the period 1906 to 1945, when Gustaf Einar Du Rietz proposed replacing epi- and hypothecium with epi- and subhymenium ; all four terms remain in use. [ 4 ] In some cases, older terminology became obsolete as better understanding of the nature of the fungal–algal relationship led to changes in their terminology. For example, after Gunnar Degelius objected to the use of gonidia for the algal partner, George Scott proposed the use of mycobiont and phycobiont for lichen components, recommendations that were generally accepted by lichenologists. [ 5 ]
This glossary includes terms defining features of lichens unique to their composite nature, such as the major components the two major components of lichens ( mycobiont and photobiont ); specialized structures in lichen physiology; descriptors of types of lichens; two- and three-dimensional shapes used to describe spores and other lichen structures; terms of position and shape; prefixes and suffixes commonly used to form lichen terms; terminology used in methods for the chemical identification of lichens; the names of 22 standard insoluble lichen pigments and their associated reference species; and "everyday" words that have a specialized meaning in lichenology. The list also includes a few historical terms that have been supplanted or are now considered obsolete. Familiarity with these terms is helpful for understanding older literature in the field. | https://en.wikipedia.org/wiki/Glossary_of_lichen_terms |
This glossary of linear algebra is a list of definitions and terms relevant to the field of linear algebra , the branch of mathematics concerned with linear equations and their representations as vector spaces .
For a glossary related to the generalization of vector spaces through modules , see glossary of module theory . | https://en.wikipedia.org/wiki/Glossary_of_linear_algebra |
The language of mathematics has a wide vocabulary of specialist and technical terms. It also has a certain amount of jargon : commonly used phrases which are part of the culture of mathematics, rather than of the subject. Jargon often appears in lectures, and sometimes in print, as informal shorthand for rigorous arguments or precise ideas. Much of this uses common English words, but with a specific non-obvious meaning when used in a mathematical sense.
Some phrases, like "in general", appear below in more than one section.
[The paper of Eilenberg and Mac Lane ( 1942 )] introduced the very abstract idea of a ' category ' — a subject then called 'general abstract nonsense'!
[ Grothendieck ] raised algebraic geometry to a new level of abstraction...if certain mathematicians could console themselves for a time with the hope that all these complicated structures were 'abstract nonsense'...the later papers of Grothendieck and others showed that classical problems...which had resisted efforts of several generations of talented mathematicians, could be solved in terms of...complicated concepts.
There are two canonical proofs that are always used to show non-mathematicians what a mathematical proof is like:
The beauty of a mathematical theory is independent of the aesthetic qualities...of the theory's rigorous expositions. Some beautiful theories may never be given a presentation which matches their beauty....Instances can also be found of mediocre theories of questionable beauty which are given brilliant, exciting expositions....[Category theory] is rich in beautiful and insightful definitions and poor in elegant proofs....[The theorems] remain clumsy and dull....[Expositions of projective geometry ] vied for one another in elegance of presentation and in cleverness of proof....In retrospect, one wonders what all the fuss was about. Mathematicians may say that a theorem is beautiful when they really mean to say that it is enlightening. We acknowledge a theorem's beauty when we see how the theorem 'fits' in its place....We say that a proof is beautiful when such a proof finally gives away the secret of the theorem....
Many of the results mentioned in this paper should be considered "folklore" in that they merely formally state ideas that are well-known to researchers in the area, but may not be obvious to beginners and to the best of my knowledge do not appear elsewhere in print.
Since half a century we have seen arise a crowd of bizarre functions which seem to try to resemble as little as possible the honest functions which serve some purpose....Nay more, from the logical point of view, it is these strange functions which are the most general....to-day they are invented expressly to put at fault the reasonings of our fathers....
[The Dirichlet function ] took on an enormous importance...as giving an incentive for the creation of new types of function whose properties departed completely from what intuitively seemed admissible. A celebrated example of such a so-called 'pathological' function...is the one provided by Weierstrass ....This function is continuous but not differentiable .
Although ultimately every mathematical argument must meet a high standard of precision, mathematicians use descriptive but informal statements to discuss recurring themes or concepts with unwieldy formal statements. Note that many of the terms are completely rigorous in context.
Norbert A'Campo of the University of Basel once asked Grothendieck about something related to the Platonic solids . Grothendieck advised caution. The Platonic solids are so beautiful and so exceptional, he said, that one cannot assume such exceptional beauty will hold in more general situations.
The formal language of proof draws repeatedly from a small pool of ideas, many of which are invoked through various lexical shorthands in practice.
Let V be a finite-dimensional vector space over k ....Let ( e i ) 1≤ i ≤ n be a basis for V ....There is an isomorphism of the polynomial algebra k [ T ij ] 1≤ i , j ≤ n onto the algebra Sym k ( V ⊗ V * )....It extends to an isomorphism of k [ GL n ] to the localized algebra Sym k ( V ⊗ V * ) D , where D = det( e i ⊗ e j * )....We write k [ GL ( V )] for this last algebra. By transport of structure, we obtain a linear algebraic group GL ( V ) isomorphic to GL n .
Mathematicians have several phrases to describe proofs or proof techniques. These are often used as hints for filling in tedious details.
This section features terms used across different areas in mathematics , or terms that do not typically appear in more specialized glossaries. For the terms used only in some specific areas of mathematics, see glossaries in Category:Glossaries of mathematics . | https://en.wikipedia.org/wiki/Glossary_of_mathematical_jargon |
Most of the terms listed in Wikipedia glossaries are already defined and explained within Wikipedia itself. However, glossaries like this one are useful for looking up, comparing and reviewing large numbers of terms together. You can help enhance this page by adding new terms or writing definitions for existing ones.
This glossary of mechanical engineering terms pertains specifically to mechanical engineering and its sub-disciplines. For a broad overview of engineering, see glossary of engineering . | https://en.wikipedia.org/wiki/Glossary_of_mechanical_engineering |
This glossary of mycology is a list of definitions of terms and concepts relevant to mycology , the study of fungi . Terms in common with other fields, if repeated here, generally focus on their mycology-specific meaning. Related terms can be found in glossary of biology and glossary of botany , among others. List of Latin and Greek words commonly used in systematic names and Botanical Latin may also be relevant, although some prefixes and suffixes very common in mycology are repeated here for clarity.
an-
acidophilic
pleuroacrogenous
attached, adherent
pl. aethalia
Imperfect state
apical veil
pl. antheridia, antherid
acro-
apodal, apodous, sessile
pl. apothecia, discocarp
applanate
pl. appresoria
hydrofungi
aerole
thallic-arthric
asco-, ascidi-
ascocarp; pl. ascomata
Ascomycetes, sac fungi
pl. asci
vegetative, somatic
basidiocarp, pl. basidiomata
Basidiomycetes
pl. basidia
gemmation
sphaeridium
carpo-, -carp
Catenulate
Chytridomycetes
cirrhus; spore horn
clamp, fibula
pl. cleistothecia
pl. columellae
pl. conidiomata
fertile hypha
pl. conidia
rind
ascus crook
crustaceous
pl. cyphellae
Cystidia
ringworm, tinea
dicaryotic, secondary mycelium
dimorphism
cup fungi
eucarpous
allochthonous
Falciform
zymosis
filamentose
flexuose
basal cell
fructicole
fruticole
mycetophagous
fungous
pl. fungi
pl. gemmae
pl. glebae
guttiferous
guttula
Gymnomycetes
pl. gymnothecia
gyrose
pl. haustoria
heterocaryotic
heterocont, Straminipila
pl. hila
homocaryotic
pl. hyphae
Hyphales
resting spore
protothallus
pl. isidia
isocont
karya-, karyo-, cary-, carya-, caryo-
caryogamy, nuclear fusion
basal body
pl. lamellae
lanose
lentiform
lichenen, moss starch
xylogenous
luniform
bioluminescent fungi
macular, maculose
pl. merosporangia
micronemous
Fungi imperfecti; Deuteromycetes; ana-holomorph; conidial fungi; asexual fungi
mould, Micromycetes, microfungi
monocaryotic
mucose, mucous
mycet-, myceto-, myco-
pl. mycelia
mycetismus, mushroom poisoning
madura foot, maduramycosis
funga
pl. mycoses
Myxomycetes
vermivorous
pl. oogonia
Peronosporomycetes
archil, orcein
pl. opercula
pl. paraphyses
pl. penicilli
pyrenocarp; pl. perithecia
race, strain, biotype
mushroom cap
polymorphic
potato late blight, potato murrain
propagulum
Pseudomycetes
pl. pseudoparenchymata
pl. pseudostromata
Fuzzball, puff-ball
punctate
pl. pycnidia
piriform
fabiform
Cryptomycota
saprogen, saprotroph
sclerotia
scutiform
pl. septa
pl. somata
pl. soredia
pl. sori
spinuous
apical body
spori-, sporo-, -spore
pl. sporangiola
pl. sporangia
fruit body, fruiting body
pl. sterigmata
pl. stromata
pl. synnemata
Perfect state
pl. thalli
torulous, torose, moniliform
mycose, mushroom sugar
tubercule
tuberculate
xylophagous fungus
swarm spore, zoöspore
Zygomycetes
zymurgy | https://en.wikipedia.org/wiki/Glossary_of_mycology |
This glossary of nanotechnology is a list of definitions of terms and concepts relevant to nanotechnology , its sub-disciplines, and related fields.
For more inclusive glossaries concerning related fields of science and technology, see Glossary of chemistry terms , Glossary of physics , Glossary of biology , and Glossary of engineering . | https://en.wikipedia.org/wiki/Glossary_of_nanotechnology |
This is a glossary of concepts and results in number theory , a field of mathematics . Concepts and results in arithmetic geometry and diophantine geometry can be found in Glossary of arithmetic and diophantine geometry .
See also List of number theory topics . | https://en.wikipedia.org/wiki/Glossary_of_number_theory |
This is a glossary of some terms used in various branches of mathematics that are related to the fields of order , lattice , and domain theory . Note that there is a structured list of order topics available as well. Other helpful resources might be the following overview articles:
In the following, partial orders will usually just be denoted by their carrier sets. As long as the intended meaning is clear from the context, ≤ {\displaystyle \,\leq \,} will suffice to denote the corresponding relational symbol, even without prior introduction. Furthermore, < will denote the strict order induced by ≤ . {\displaystyle \,\leq .}
The definitions given here are consistent with those that can be found in the following standard reference books:
Specific definitions: | https://en.wikipedia.org/wiki/Glossary_of_order_theory |
This glossary of power electronics is a list of definitions of terms and concepts related to power electronics in general and power electronic capacitors in particular. For more definitions in electric engineering, see Glossary of electrical and electronics engineering . For terms related to engineering in general, see Glossary of engineering .
The glossary terms fit in the following categories in power electronics:
f p = 1 t p τ = π L C {\textstyle f_{p}={\frac {1}{t_{p}}}\qquad \tau =\pi {\sqrt {LC}}}
This article incorporates text from this source, which is in the public domain : IS 1885-27: Electrotechnical vocabulary . 27. New Delhi, Bureau of Indian Standards . 2008.
This article incorporates text from this source, which is in the public domain : IS 13648: Power electronics capacitors . New Delhi, Bureau of Indian Standards . 1993. | https://en.wikipedia.org/wiki/Glossary_of_power_electronics |
This page is a glossary of Prestressed concrete terms . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] | https://en.wikipedia.org/wiki/Glossary_of_prestressed_concrete_terms |
This glossary of statistics and probability is a list of definitions of terms and concepts used in the mathematical sciences of statistics and probability , their sub-disciplines, and related fields. For additional related terms, see Glossary of mathematics and Glossary of experimental design .
Also confidence coefficient .
Also correlation coefficient .
Also expectation , mathematical expectation , first moment , or simply mean or average .
Also midspread , middle 50% , and H-spread .
Also moving mean and rolling mean . | https://en.wikipedia.org/wiki/Glossary_of_probability_and_statistics |
This is a glossary for the terminology applied in the foundations of quantum mechanics and quantum metaphysics , collectively called quantum philosophy , a subfield of philosophy of physics .
Note that this is a highly debated field, hence different researchers may have different definitions on the terms.
List of interpretations:
Early researchers (before the 1950s):
1950s–2010s:
2000s or later: | https://en.wikipedia.org/wiki/Glossary_of_quantum_philosophy |
This is a list of terms and symbols used in scientific names for organisms, and in describing the names. For proper parts of the names themselves, see List of Latin and Greek words commonly used in systematic names . Note that many of the abbreviations are used with or without a stop .
The main ranks are kingdom ( regnum ), phylum or division ( divisio ), class ( classis ), order ( ordo ), family ( familia ), genus and species . The ranks of section and series are also used in botany for groups within genera, while section is used in zoology for a division of an order. Further levels in the hierarchy can be made by the addition of prefixes such as sub-, super-, infra-, and so on.
Divisions such as "morph", "form", "variety", "strain", "breed", " cultivar ", hybrid (nothospecies) and " landrace " are used to describe various sub-specific groups in different fields.
It is possible for a clade to be unranked, for example Psoroptidia (Yunker, 1955) and the SAR supergroup . Sometimes a rank is described as clade where the traditional hierarchy cannot accommodate it.
Note that in zoology the English descriptions, such as "conserved name", for example, are acceptable and generally used. These descriptions can be classified between accepted names ( nom. cons., nom. nov., nom. prot. ) and unaccepted combinations for different reasons ( nom. err., nom. illeg., nom. nud., nom. rej., nom. supp., nom. van. ), with some cases in between regarding the use ( nom. dub. : used but not fully accepted; nom. obl. : accepted but not fully used, so it yields precedence to a nom. prot ). | https://en.wikipedia.org/wiki/Glossary_of_scientific_naming |
This glossary of structural engineering terms pertains specifically to structural engineering and its sub-disciplines. Please see Glossary of engineering for a broad overview of the major concepts of engineering.
Most of the terms listed in glossaries are already defined and explained within itself. However, glossaries like this one are useful for looking up, comparing and reviewing large numbers of terms together. You can help enhance this page by adding new terms or writing definitions for existing ones.
[ 27 ] [ 28 ] [ 29 ] | https://en.wikipedia.org/wiki/Glossary_of_structural_engineering |
This is a glossary of tensor theory . For expositions of tensor theory from different points of view, see:
For some history of the abstract theory see also multilinear algebra .
This avoids the initial use of components, and is distinguished by the explicit use of the tensor product symbol.
See: | https://en.wikipedia.org/wiki/Glossary_of_tensor_theory |
The COVID-19 pandemic has created and popularized many terms relating to disease and videoconferencing .
Main article: Anthropause
See also: Asymptomatic
Main article: Booster dose
Main article: Comirnaty
Main article: Community transmission
Main article: Contact tracing
Main article: Covidiot
Main article: COVID-19 lockdowns
Main article: Cytokine Storm
Main article: Doomscrolling
Main article: Essential worker
Main article: Flattening the curve
Main article: Flurona
Main article: Fomite
Main article: Herd immunity
Main article: Heterologous vaccine
Main article: Host cell
Main article: Hygiene theater
Main article: Immunity (medical)
Main article: Incubation period
Main article: Long-hauler
Main article: Maskne
Main article: PCR test
Main article: Quarantini
Main article: R naught
Main article: Serology test
Main article: Seroprevalence
Main article: Social distancing
Main article: Superspreader
Main article: Twindemic
Main article: Viral load
Main article: Zero-COVID
Main article: Zoonotic
Main article: Zoom (software)
Main article: Zoom fatigue
Main article: Zoombombing | https://en.wikipedia.org/wiki/Glossary_of_the_COVID-19_pandemic |
This glossary of virology is a list of definitions of terms and concepts used in virology , the study of viruses , particularly in the description of viruses and their actions. Related fields include microbiology , molecular biology , and genetics .
Often simply called an antiviral .
Also simply called a phage .
Also cytopathogenic effect .
Also called a gag .
Also sometimes called a mycophage .
Also called antigenic imprinting and the Hoskins effect .
Also called passaging .
Also called viral burden and viral titre .
Also called a viral particle . | https://en.wikipedia.org/wiki/Glossary_of_virology |
A glovebox (or glove box ) is a sealed container that is designed to allow one to manipulate objects where a separate atmosphere is desired. Built into the sides of the glovebox are gloves arranged in such a way that the user can place their hands into the gloves and perform tasks inside the box without breaking containment. Part or all of the box is usually transparent to allow the user to see what is being manipulated. A smaller antechamber compartment is used to transport items into or out of the main chamber without compromising the internal environment. Antechambers are much smaller than the main chambers so they can be exposed to ambient conditions more often and achieve inert conditions quickly. [ 1 ]
Two types of gloveboxes exist. The first allows a person to work with hazardous substances, such as radioactive materials or infectious disease agents, and the second allows manipulation of substances that must be contained within a very high purity inert atmosphere, such as argon or nitrogen . It is also possible to use a glovebox for manipulation of items in a vacuum chamber .
The gas in a glovebox is pumped through a series of treatment devices which remove solvents , water and oxygen from the gas. Copper metal (or some other finely divided metal) is commonly used to remove oxygen, this oxygen removing column is normally regenerated by passing a hydrogen / nitrogen mixture through it while it is heated: the water formed is passed out of the box with the excess hydrogen and nitrogen. It is common to use molecular sieves to remove water by absorbing it in the molecular sieves' pores. Such a box is often used by organometallic chemists to transfer dry solids from one container to another container.
An alternative to using a glovebox for air sensitive work is to employ Schlenk methods using a Schlenk line . One disadvantage of working in a glovebox is that organic solvents will attack the plastic seals. As a result, the box will start to leak and water and oxygen can then enter the box. Another disadvantage of a glovebox is that oxygen and water can diffuse through the plastic gloves. Also, coordinating solvents, such as tetrahydrofuran and dichloromethane , can bind irreversibly to the copper catalyst, reducing its effectiveness. One way to prolong the lifespan of the glovebox and catalyst is to turn off circulation when using solvents, followed by purging when work involving solvents is finished.
Inert atmosphere gloveboxes are typically kept at a higher pressure than the surrounding air, so that any microscopic leaks are mostly leaking inert gas out of the box instead of letting air in.
At the now-deactivated Rocky Flats Plant , which manufactured plutonium triggers , also called "pits", production facilities consisted of linked stainless steel gloveboxes up to 64 feet, or 20 meters, in length, which contained the equipment which forged and machined the trigger parts. The gloves were lead -lined. Other materials used in the gloveboxes included acrylic viewing windows and Benelex shielding composed of wood fiber and plastic which shielded against neutron radiation . Manipulation of the lead-lined gloves was onerous work.
Some gloveboxes for radioactive work are under inert conditions, for instance, one nitrogen-filled box contains an argon-filled box. The argon box is fitted with a gas treatment system to keep the gas very pure to enable electrochemical experiments in molten salts. [ 2 ]
Gloveboxes are also used in the biological sciences when dealing with anaerobes or high- biosafety level pathogens.
Gloveboxes used for hazardous materials are generally maintained at a lower pressure than the surrounding atmosphere, so that microscopic leaks result in air intake rather than hazard outflow. Gloveboxes used for hazardous materials generally incorporate HEPA filters into the exhaust, to keep the hazard contained. | https://en.wikipedia.org/wiki/Glovebox |
A glow discharge is a plasma formed by the passage of electric current through a gas. It is often created by applying a voltage between two electrodes in a glass tube containing a low-pressure gas. When the voltage exceeds a value called the striking voltage , the gas ionization becomes self-sustaining, and the tube glows with a colored light. The color depends on the gas used.
Glow discharges are used as a source of light in devices such as neon lights , cold cathode fluorescent lamps and plasma-screen televisions . Analyzing the light produced with spectroscopy can reveal information about the atomic interactions in the gas, so glow discharges are used in plasma physics and analytical chemistry . They are also used in the surface treatment technique called sputtering .
Conduction in a gas requires charge carriers, which can be either electrons or ions. Charge carriers come from ionizing some of the gas molecules. In terms of current flow, glow discharge falls between dark discharge and arc discharge.
Below the breakdown voltage there is little to no glow and the electric field is uniform. When the electric field increases enough to cause ionization, the Townsend discharge starts. When a glow discharge develops, the electric field is considerably modified by the presence of positive ions; the field is concentrated near the cathode. The glow discharge starts as a normal glow. As the current is increased, more of the cathode surface is involved in the glow. When the current is increased above the level where the entire cathode surface is involved, the discharge is known as an abnormal glow. If the current is increased still further, other factors come into play and an arc discharge begins. [ 2 ]
The simplest type of glow discharge is a direct-current glow discharge. In its simplest form, it consists of two electrodes in a cell held at low pressure (0.1–10 torr ; about 1/10000 to 1/100 of atmospheric pressure). A low pressure is used to increase the mean free path ; for a fixed electric field, a longer mean free path allows a charged particle to gain more energy before colliding with another particle. The cell is typically filled with neon, but other gases can also be used. An electric potential of several hundred volts is applied between the two electrodes. A small fraction of the population of atoms within the cell is initially ionized through random processes, such as thermal collisions between atoms or by gamma rays . The positive ions are driven towards the cathode by the electric potential, and the electrons are driven towards the anode by the same potential. The initial population of ions and electrons collides with other atoms, exciting or ionizing them. As long as the potential is maintained, a population of ions and electrons remains.
Some of the ions' kinetic energy is transferred to the cathode. This happens partially through the ions striking the cathode directly. The primary mechanism, however, is less direct. Ions strike the more numerous neutral gas atoms, transferring a portion of their energy to them. These neutral atoms then strike the cathode. Whichever species (ions or atoms) strike the cathode, collisions within the cathode redistribute this energy resulting in electrons ejected from the cathode. This process is known as secondary electron emission. Once free of the cathode, the electric field accelerates electrons into the bulk of the glow discharge. Atoms can then be excited by collisions with ions, electrons, or other atoms that have been previously excited by collisions.
Once excited, atoms will lose their energy fairly quickly. Of the various ways that this energy can be lost, the most important is radiatively, meaning that a photon is released to carry the energy away. In optical atomic spectroscopy , the wavelength of this photon can be used to determine the identity of the atom (that is, which chemical element it is) and the number of photons is directly proportional to the concentration of that element in the sample. Some collisions (those of high enough energy) will cause ionization. In atomic mass spectrometry , these ions are detected. Their mass identifies the type of atoms and their quantity reveals the amount of that element in the sample.
The illustrations to the right shows the main regions that may be present in a glow discharge. Regions described as "glows" emit significant light; regions labeled as "dark spaces" do not. As the discharge becomes more extended (i.e., stretched horizontally in the geometry of the illustrations), the positive column may become striated . That is, alternating dark and bright regions may form. Compressing the discharge horizontally will result in fewer regions. The positive column will be compressed while the negative glow will remain the same size, and, with small enough gaps, the positive column will disappear altogether. In an analytical [ clarification needed ] glow discharge, the discharge is primarily a negative glow with dark region above and below it.
The cathode layer begins with the Aston dark space, and ends with the negative glow region. The cathode layer shortens with increased gas pressure. The cathode layer has a positive space charge and a strong electric field. [ 3 ] [ 4 ]
Electrons leave the cathode with an energy of about 1 eV, which is not enough to ionize or excite atoms, leaving a thin dark layer next to the cathode. [ 3 ]
Electrons from the cathode eventually attain enough energy to excite atoms. These excited atoms quickly fall back to the ground state, emitting light at a wavelength corresponding to the difference between the energy bands of the atoms. This glow is seen very near the cathode. [ 3 ]
As electrons from the cathode gain more energy, they tend to ionize, rather than excite atoms. Excited atoms quickly fall back to ground level emitting light, however, when atoms are ionized, the opposite charges are separated, and do not immediately recombine. This results in more ions and electrons, but no light. [ 3 ] This region is sometimes called Crookes dark space, and sometimes referred to as the cathode fall , because the largest voltage drop in the tube occurs in this region.
The ionization in the cathode dark space results in a high electron density, but slower electrons, making it easier for the electrons to recombine with positive ions, leading to intense light, through a process called bremsstrahlung radiation . [ 3 ]
As the electrons keep losing energy, less light is emitted, resulting in another dark space. [ 3 ]
The anode layer begins with the positive column, and ends at the anode. The anode layer has a negative space charge and a moderate electric field. [ 3 ]
With fewer ions, the electric field increases, resulting in electrons with energy of about 2 eV, which is enough to excite atoms and produce light. With longer glow discharge tubes, the longer space is occupied by a longer positive column, while the cathode layer remains the same. [ 3 ] For example, with a neon sign, the positive column occupies almost the entire length of the tube.
An electric field increase results in the anode glow. [ 3 ]
Fewer electrons results in another dark space. [ 3 ]
Bands of alternating light and dark in the positive column are called striations . There is no universal mechanism explaining the striations for all conditions of gas and pressure producing them, but recent theoretical and modelling studies, supported with experimental results, mention the importance of the Dufour effect . [ 5 ]
In addition to causing secondary emission, positive ions can strike the cathode with sufficient force to eject particles of the material from which the cathode is made. This process is called sputtering and it gradually ablates the cathode. Sputtering is useful when using spectroscopy to analyze the composition of the cathode, as is done in Glow-discharge optical emission spectroscopy . [ 6 ]
However, sputtering is not desirable when glow discharge is used for lighting, because it shortens the life of the lamp. For example, neon signs have hollow cathodes designed to minimize sputtering, and contain charcoal to continuously remove undesired ions and atoms. [ 7 ]
In the context of sputtering, the gas in the tube is called "carrier gas," because it carries the particles from the cathode. [ 6 ]
Because of sputtering occurring at the cathode, the colors emitted from regions near the cathode are quite different from the anode. Particles sputtered from the cathode are excited and emit radiation from the metals and oxides that make up the cathode. The radiation from these particles combines with radiation from excited carrier gas, giving the cathode region a white or blue color, while in the rest of the tube, radiation is only from the carrier gas and tends to be more monochromatic. [ 6 ]
Electrons near the cathode are less energetic than the rest of the tube. Surrounding the cathode is a negative field, which slows electrons as they are ejected from the surface. Only those electrons with the highest velocity are able to escape this field, and those without enough kinetic energy are pulled back into the cathode. Once outside the negative field, the attraction from the positive field begins to accelerate these electrons toward the anode. During this acceleration electrons are deflected and slowed down by positive ions speeding toward the cathode, which, in turn, produces bright blue-white bremsstrahlung radiation in the negative glow region. [ 8 ]
Glow discharges can be used to analyze the elemental, and sometimes molecular, composition of solids, liquids, and gases, but elemental analysis of solids is the most common. In this arrangement, the sample is used as the cathode. As mentioned earlier, gas ions and atoms striking the sample surface knock atoms off of it, a process known as sputtering.
The sputtered atoms, now in the gas phase, can be detected by atomic absorption , but this is a comparatively rare strategy. Instead, atomic emission and mass spectrometry are usually used.
Collisions between the gas-phase sample atoms and the plasma gas pass energy to the sample atoms. This energy can excite the atoms, after which they can lose their energy through atomic emission. By observing the wavelength of the emitted light, the atom's identity can be determined. By observing the intensity of the emission, the concentration of atoms of that type can be determined.
Energy gained through collisions can also ionize the sample atoms. The ions can then be detected by mass spectrometry. In this case, it is the mass of the ions that identify the element and the number of ions that reflect the concentration. This method is referred to as glow discharge mass spectrometry (GDMS) and it has detection limits down to the sub-ppb range for most elements that are nearly matrix-independent.
Both bulk and depth analysis of solids may be performed with glow discharge. Bulk analysis assumes that the sample is fairly homogeneous and averages the emission or mass spectrometric signal over time. Depth analysis relies on tracking the signal in time, therefore, is the same as tracking the elemental composition in depth.
Depth analysis requires greater control over operational parameters. For example, conditions (current, potential, pressure) need to be adjusted so that the crater produced by sputtering is flat bottom (that is, so that the depth analyzed over the crater area is uniform). In bulk measurement, a rough or rounded crater bottom would not adversely impact analysis. Under the best conditions, depth resolution in the single nanometer range has been achieved (in fact, within-molecule resolution has been demonstrated). [ citation needed ]
The chemistry of ions and neutrals in vacuum is called gas phase ion chemistry and is part of the analytical study that includes glow discharge.
In analytical chemistry , glow discharges are usually operated in direct-current mode. For direct-current, the cathode (which is the sample in solids analysis) must be conductive. In contrast, analysis of a non conductive cathode requires the use of a high frequency alternating current.
The potential, pressure, and current are interrelated. Only two can be directly controlled at once, while the third must be allowed to vary. The pressure is most typically held constant, but other schemes may be used. The pressure and current may be held constant, while potential is allowed to vary. The pressure and voltage may be held constant while the current is allowed to vary. The power (product of voltage and current) may be held constant while the pressure is allowed to vary.
Glow discharges may also be operated in radio-frequency. The use of this frequency will establish a negative DC-bias voltage on the sample surface. The DC-bias is the result of an alternating current waveform that is centered about negative potential; as such it more or less represent the average potential residing on the sample surface. Radio-frequency has ability to appear to flow through insulators (non-conductive materials).
Both radio-frequency and direct-current glow discharges can be operated in pulsed mode, where the potential is turned on and off. This allows higher instantaneous powers to be applied without excessively heating the cathode. These higher instantaneous powers produce higher instantaneous signals, aiding detection. Combining time-resolved detection with pulsed powering results in additional benefits. In atomic emission, analyte atoms emit during different portions of the pulse than background atoms, allowing the two to be discriminated. Analogously, in mass spectrometry, sample and background ions are created at different times.
An interesting application for using glow discharge was described in a 2002 scientific paper by Ryes, Ghanem et al. [ 9 ] According to a Nature news article describing the work, [ 10 ] researchers at Imperial College London demonstrated how they built a mini-map that glows along the shortest route between two points. The Nature news article describes the system as follows:
The approach itself provides a novel visible analog computing approach for solving a wide class of maze searching problems based on the properties of lighting up of a glow discharge in a microfluidic chip.
In the mid-20th century, prior to the development of solid state components such as Zener diodes , voltage regulation in circuits was often accomplished with voltage-regulator tubes , which used glow discharge. | https://en.wikipedia.org/wiki/Glow_discharge |
A glow stick , also known as a light stick , chem light , light wand , light rod , and rave light , is a self-contained, short-term light-source. It consists of a translucent plastic tube containing isolated substances that, when combined, make light through chemiluminescence . [ 1 ] The light cannot be turned off and can be used only once. The used tube is then thrown away. Glow sticks are often used for recreation, such as for events, camping, outdoor exploration, and concerts. Glow sticks are also used for light in military and emergency services applications. Industrial uses include marine, transportation, and mining.
Bis(2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl)oxalate , trademarked "Cyalume", was invented in 1971 by Michael M. Rauhut, [ 2 ] of American Cyanamid , based on work by Edwin A. Chandross and David Iba Sr. of Bell Labs . [ 3 ] [ 4 ]
Other early work on chemiluminescence was carried out at the same time, by researchers under Herbert Richter at China Lake Naval Weapons Center . [ 5 ] [ 6 ]
Several US patents for glow stick-type devices were issued in 1973–74. [ 7 ] [ 8 ] [ 9 ] A later 1976 patent [ 10 ] recommended a single glass ampoule that is suspended in a second substance, that when broken and mixed together, provide the chemiluminescent light. The design also included a stand for the signal device so it could be thrown from a moving vehicle and remain standing in an upright position on the road. The idea was this would replace traditional emergency roadside flares and would be superior, since it was not a fire hazard, would be easier and safer to deploy, and would not be made ineffective if struck by passing vehicles. This design, with its single glass ampoule inside a plastic tube filled with a second substance that when bent breaks the glass and then is shaken to mix the substances, most closely resembles the typical glow stick sold today. [ citation needed ]
In the early 1980s the majority of glow sticks were produced in Novato, California by Omniglow Corp. Omniglow completed a leveraged buyout of American Cyanamid's chemical light division in 1994 and became the leading supplier of glow sticks worldwide until going out of business in 2014. Most glow sticks seen today are now made in China. [ 11 ]
Glow sticks are waterproof, do not use batteries, consume no oxygen, generate no or negligible heat, produce neither spark nor flame, can tolerate high pressures such as those found under water, are inexpensive, and are reasonably disposable. This makes them ideal as light sources and light markers by military forces, campers , spelunkers , and recreational divers . [ 12 ]
Glowsticking is the use of glow sticks in dancing [ 13 ] (such as in glow poi and wotagei ). They are frequently used for entertainment at parties (in particular raves ), concerts , and dance clubs . They are used by marching band conductors for evening performances; glow sticks are also used in festivals and celebrations around the world. Glow sticks also serve multiple functions as toys, readily visible night-time warnings to motorists, and luminous markings that enable parents to keep track of their children. Another use is for balloon-carried light effects . Glow sticks are also used to create special effects in low light photography and film. [ 14 ]
The Guinness Book of Records recorded the world's largest glow stick was cracked at 150 metres (492 ft 2 in) tall. It was created by the University of Wisconsin–Whitewater 's Chemistry Department to celebrate the school's sesquicentennial, or 150th birthday in Whitewater, Wisconsin and cracked on 9 September 2018. [ 15 ]
Glow sticks are used for outdoor recreation, often used at night for marking. Scuba divers use diving-rated glow sticks to mark themselves during night dives. This is done to enable visibility of bioluminescent marine organisms, which cannot be seen while a bright dive light is illuminated. Glow sticks are used on backpacks, tent pegs, and on jackets during overnight camping expeditions. Often, glow sticks are recommended as an addition to survival kits .
There are specific industrial uses of glow sticks, which are often used as a light source in circumstances where electric lighting and LEDs are not best suited. For example, in the mining industry, glow sticks are required for emergency evacuation in the case of a gas leak. Use of an electric light source in this case may cause an unintended explosion. Chemiluminescence, the type of light used in glow sticks, is a "cold-light" and does not use electricity, and will not cause a gas leak to ignite.
Glow sticks are also used worldwide in the marine industry, often used as fishing lures in long-line, recreational, and commercial fishing, as well as for personnel safety.
Glow sticks were originally invented by the US military, [ 16 ] and are an essential part of military operations across land and sea, where they are more often referred to as chem lights. Glow sticks are also used within police tactical units , as light sources during night operations or close-quarters combat in dark areas. They are also used to mark secured areas or objects of note. When worn, they can be used to identify friendly soldiers during nighttime operations. [ 17 ] For search and rescue operations, glow sticks are often used during Man Overboard rescue scenarios to create a glowing trail back to the last known location of someone who is lost at sea.
Glow sticks are used by police , fire , and emergency medical services as light sources, similar to their military applications. Often, emergency rescue crews will hand out glow sticks in order to keep track of people at night, who may not have access to their own lighting. Glow sticks are sometimes attached to life vests and lifeboats on passenger and commercial vessels, to ensure night time visibility.
Glow sticks are often part of emergency kits to provide basic lighting and provide ease of identification in dark areas. They can be found in emergency lighting kits in buildings, public transportation vehicles, and subway stations .
Glow sticks emit light when two chemicals are mixed. The reaction between the two chemicals is catalyzed by a base, usually sodium salicylate . [ 18 ] The sticks consist of a tiny, brittle container within a flexible outer container. Each container holds a different solution. When the outer container is flexed, the inner container breaks, allowing the solutions to combine, causing the necessary chemical reaction. After breaking, the tube is shaken to thoroughly mix the components.
The glow stick contains two chemicals, a base catalyst, and a suitable dye ( sensitizer , or fluorophor ). This creates an exergonic reaction . The chemicals inside the plastic tube are a mixture of the dye, the base catalyst, and diphenyl oxalate . The chemical in the glass vial is hydrogen peroxide. By mixing the peroxide with the phenyl oxalate ester, a chemical reaction takes place, yielding two moles of phenol and one mole of peroxyacid ester ( 1,2-dioxetanedione ). [ 19 ] The peroxyacid decomposes spontaneously to carbon dioxide , releasing energy that excites the dye, which then relaxes by releasing a photon . The wavelength of the photon—the color of the emitted light—depends on the structure of the dye. The reaction releases energy mostly as light, with very little heat. [ 18 ] The reason for this is that the reverse [2 + 2] photocycloadditions of 1,2-dioxetanedione is a forbidden transition (it violates Woodward–Hoffmann rules ) and cannot proceed through a regular thermal mechanism.
By adjusting the concentrations of the two chemicals and the base, manufacturers can produce glow sticks that glow either brightly for a short amount of time or more dimly for an extended length of time. This also allows glow sticks to perform satisfactorily in hot or cold climates, by compensating for the temperature dependence of reaction. At maximum concentration (typically found only in laboratory settings), mixing the chemicals results in a furious reaction, producing large amounts of light for only a few seconds. The same effect can be achieved by adding copious amounts of sodium salicylate or other bases. Heating a glow stick also causes the reaction to proceed faster and the glow stick to glow more brightly for a brief period. Cooling a glow stick slows the reaction a small amount and causes it to last longer, but the light is dimmer. This can be demonstrated by refrigerating or freezing an active glow stick; when it warms up again, it will resume glowing. The dyes used in glow sticks usually exhibit fluorescence when exposed to ultraviolet radiation—even a spent glow stick may therefore shine under a black light .
The light intensity is high immediately after activation, then exponentially decays. Leveling of this initial high output is possible by refrigerating the glow stick before activation. [ 20 ]
A combination of two fluorophores can be used, with one in the solution and another incorporated to the walls of the container. This is advantageous when the second fluorophore would degrade in solution or be attacked by the chemicals. The emission spectrum of the first fluorophore and the absorption spectrum of the second one have to largely overlap, and the first one has to emit at shorter wavelength than the second one. A downconversion from ultraviolet to visible is possible, as is conversion between visible wavelengths (e.g., green to orange) or visible to near-infrared. The shift can be as much as 200 nm, but usually the range is about 20–100 nm longer than the absorption spectrum. [ 21 ] Glow sticks using this approach tend to have colored containers, due to the dye embedded in the plastic. Infrared glow sticks may appear dark-red to black, as the dyes absorb the visible light produced inside the container and reemit near-infrared.
On the other hand, various colors can also be achieved by simply mixing several fluorophores within the solution to achieve the desired effect. [ 18 ] [ 22 ] These various colors can be achieved due to the principles of additive color . For example, a combination of red, yellow, and green fluorophores is used in orange light sticks, [ 18 ] and a combination of several fluorescers is used in white light sticks. [ 22 ]
In glow sticks, phenol is produced as a byproduct. It is advisable to keep the mixture away from skin and to prevent accidental ingestion if the glow stick case splits or breaks. If spilled on skin, the chemicals could cause skin irritation, swelling, or, in extreme circumstances, vomiting and nausea. Some of the chemicals used in older glow sticks are carcinogens . [ 25 ] The sensitizers used are polynuclear aromatic hydrocarbons , a class of compounds known for their carcinogenic properties.
Dibutyl phthalate , a plasticizer sometimes used in glow sticks (and many plastics), has raised some health concerns. It was put on California's list of suspected teratogens in 2006. [ 26 ] Glow stick liquid contains ingredients that can act as a plasticizer, softening plastics onto which it leaks. [ 27 ] Diphenyl oxalate can sting and burn eyes, irritate and sting skin and can burn the mouth and throat if ingested.
Researchers in Brazil, concerned about waste from glowsticks used in fishing in their country, published a study in 2014 on this topic. [ 28 ] It measured the secondary reactions that continue within used glow sticks, toxicity to cells in culture, and chemical reactions with DNA in vitro. The authors found high toxicity of light stick solutions, and evidence of reactivity with DNA. They concluded that light stick solutions "are hazardous and that the health risks associated with exposure have not yet been properly evaluated."
Many glow sticks use the chemical TCPO, or trichlorophenol, which is highly toxic if inhaled or ingested and is toxic to organs if ingested or otherwise exposed. [ 29 ]
A Danish Ministry of the Environment report investigated commercially available glow sticks and found evidence of glow sticks containing dibutyl pthalate, and concluded that this is in violation of the law. [ 30 ] From the report "that substance must not be used in toys or gimmick and gag articles as according to classification it may damage fertility or the unborn child. The risk arises after repeated or longer exposure." In this consumer investigation, it was also observed that certain glow stick packaging featured images of children on the front, while the back carried a warning label stating "not suitable for children." This inconsistency may lead to consumer confusion and raises questions regarding appropriate product marketing and safety communication. [ 30 ] Products on amazon can be marketed as child safe and non toxic, but these claims are unvalidated.
Glow sticks also contribute to the plastic waste problem , as glow sticks are single-use items and made from plastic. Additionally, since the inner vial is often made from glass and the chemicals inside are dangerous if improperly handled, the plastic used for glow sticks is non-recoverable by recycling services, so glow sticks are categorized as non-recyclable waste.
Safety data sheets for individual components of glow stick formulas recommend absorbing with sawdust or other absorbent material and in particular stress the importance of keeping waste away from water sources. One should not dump used glow stick fluid down the drain.
By the 2020s, work was being done to create safer glow sticks and alternatives. Canadian company Lux Bio developed glow stick alternatives such as the Light Wand which is biodegradable and powered with bioluminescence , rather than the chemiluminescence [ 31 ] [ 32 ] and LÜMI, which is a reusable and non-toxic alternative that glows with phosphorescence [ 33 ] and is chemically and biologically inert. | https://en.wikipedia.org/wiki/Glow_stick |
The Glowing Plant project was the first crowdfunding campaign for a synthetic biology application. The project was started by the Sunnyvale -based hackerspace Biocurious as part of the DIYbio philosophy. According to the project's goals, funds were used to create a glowing Arabidopsis thaliana plant using firefly luminescence genes. Long-term ambitions (never realized) included the development of glowing trees that can be used to replace street lights, reducing CO 2 emissions by not requiring electricity.
In 2023 this concept was finally achieved, commercialized, and brought to market by Light Bio, [ 1 ] who used a fungal luminescence gene in petunias to achieve the first commercially available luminescent plants. These are currently only available in the US (as of 2024)
Using Kickstarter , the project's founders raised $484,000 on June 8, 2013. [ 2 ] This was significantly more than the initial target of $65,000.
Seeds were initially scheduled to be delivered in April 2014, and subsequently scheduled for the fall of 2014. [ 3 ] In March 2016, delivery of seeds was forecast for 2016 on the Glowing Plant website. The company encountered difficulty in producing plants that emit significant amounts of light, resulting in a transition to producing moss that emits a patchouli scent. [ 4 ] They later announced via email December 2017 that the company was permanently ceasing operations.
Biocurious planned to tweak the biobrick containing six genes, including luciferin-regenerating enzyme and luciferase from fireflies . [ 5 ] [ 6 ] During initial development, they would use Agrobacterium to test the transfer of the genetic circuit . When producing the final product, they intended to instead use a gene gun to avoid issues related to regulation of GM plants. [ 4 ] Over the course of the project, several plants were mentioned as being recipients, including Arabidopsis thaliana , Nicotiana tabacum , and roses . [ 6 ] Issues surrounding the production included the difficulty of moving the six component genes of the metabolic pathway , increasing the dim light produced by the plant following insertion, and preventing the pathway from being silenced . [ 4 ]
The project generated widespread media attention and a discussion of appropriate uses of biotechnology. [ 7 ] As a result of the controversy, Kickstarter decided to prohibit genetically modified organisms as rewards to project backers. [ 8 ]
Though the Animal and Plant Health Inspection Service (APHIS) has shown no regulatory concerns about the project, some synthetic biologists and policy researchers have questioned the project's feasibility and impact on future oversight or public opinion of synthetic biology. In particular, if the company were to encourage backers to use a genetic DIY kit themselves, additional regulatory oversight would likely occur. [ 9 ] | https://en.wikipedia.org/wiki/Glowing_Plant_project |
Applying line voltage across a pickled cucumber causes it to glow. A moist pickle contains salt as a result of the pickling process, which allows it to conduct electricity. Sodium (or other) ions within the pickle emit light as a result of atomic electron transitions , although it is not clear why the luminescence occurs at one end of the pickle. [ 1 ]
The glowing pickle is used to demonstrate ionic conduction and atomic emission in chemistry classes, [ 2 ] and also as a demonstration in lighting classes. [ 3 ]
The first known fully documented demonstration was in a 1989 report from Digital Equipment Corporation . [ 4 ] Although this was published as a full technical note and written up as a scientific paper, the publication date, April Fools' Day of that year, gives some indication as to the light-hearted nature of the document.
This chemistry -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glowing_pickle_demonstration |
A splint (or spill or splinter ) is a simple piece of equipment used in scientific laboratories . Splints are typically long, thin strips of wood, about 6 inches (15 cm) long and ¼ inch (6 mm) wide, and are consumable but inexpensive. They are typically used for tasks such as lighting bunsen burners , as the length of the splint allows a flame to be lit without risk to the user's hand, should the burner flare back. Another use for splints are chemical identification of various gases , and splints are also used to teach simple chemical principles in schools and homes.
Some gases are hard to distinguish by sight or smell alone. For example, hydrogen, oxygen and nitrogen are all colourless and odourless. Several laboratory experiments are capable of producing relatively pure gas as an end product, and it may be useful to demonstrate the chemical identity of that gas. Burning splints or glowing splints can be used to identify whether a gas is flammable , whether it is oxidising , or whether it is chemically inert .
These tests are not safe for completely unidentified gases, as the energy of their explosion could be beyond the safe confinement of a fragile glass tube. This means that they are really only useful as a demonstration of a gas that is already strongly suspected, and so is known to be safe. In a high school chemistry class, a typical use would be to show the presence of hydrogen (after electrolysis of water , or by reacting a metal with an acid ).
A splint is lit and held near the opening of the tube, then the stopper is removed to expose the splint to the gas.
If the gas is flammable , the mixture ignites. [ 1 ] This test is most commonly used to identify hydrogen , which results with a distinctive 'squeaky pop' sound. [ 2 ] Hydrogen is easily ignited and used to definitively conclude what the gas actually is. [ 3 ] Further analytical chemistry techniques can clarify the identity of the gas in question.
The glowing splint test is a test for an oxidising gas, such as oxygen . [ 4 ] In this test, a splint is lit, allowed to burn for a few seconds, then blown out by mouth or by shaking. Whilst the ember at the tip is still glowing hot, the splint is introduced to the gas sample that has been trapped in a vessel. [ 4 ]
Upon exposure to concentrated oxygen gas, the glowing ember flares, and re-ignites to produce a sustained flame. [ 4 ] [ 5 ] The more concentrated the oxygen, the faster the wood burns, and the more intense the flame. This test is not specific for oxygen, but will react similarly for any oxidising gas (such as nitrous oxide ) that supports the combustion of the splint. | https://en.wikipedia.org/wiki/Glowing_splint |
A splint (or spill or splinter ) is a simple piece of equipment used in scientific laboratories . Splints are typically long, thin strips of wood, about 6 inches (15 cm) long and ¼ inch (6 mm) wide, and are consumable but inexpensive. They are typically used for tasks such as lighting bunsen burners , as the length of the splint allows a flame to be lit without risk to the user's hand, should the burner flare back. Another use for splints are chemical identification of various gases , and splints are also used to teach simple chemical principles in schools and homes.
Some gases are hard to distinguish by sight or smell alone. For example, hydrogen, oxygen and nitrogen are all colourless and odourless. Several laboratory experiments are capable of producing relatively pure gas as an end product, and it may be useful to demonstrate the chemical identity of that gas. Burning splints or glowing splints can be used to identify whether a gas is flammable , whether it is oxidising , or whether it is chemically inert .
These tests are not safe for completely unidentified gases, as the energy of their explosion could be beyond the safe confinement of a fragile glass tube. This means that they are really only useful as a demonstration of a gas that is already strongly suspected, and so is known to be safe. In a high school chemistry class, a typical use would be to show the presence of hydrogen (after electrolysis of water , or by reacting a metal with an acid ).
A splint is lit and held near the opening of the tube, then the stopper is removed to expose the splint to the gas.
If the gas is flammable , the mixture ignites. [ 1 ] This test is most commonly used to identify hydrogen , which results with a distinctive 'squeaky pop' sound. [ 2 ] Hydrogen is easily ignited and used to definitively conclude what the gas actually is. [ 3 ] Further analytical chemistry techniques can clarify the identity of the gas in question.
The glowing splint test is a test for an oxidising gas, such as oxygen . [ 4 ] In this test, a splint is lit, allowed to burn for a few seconds, then blown out by mouth or by shaking. Whilst the ember at the tip is still glowing hot, the splint is introduced to the gas sample that has been trapped in a vessel. [ 4 ]
Upon exposure to concentrated oxygen gas, the glowing ember flares, and re-ignites to produce a sustained flame. [ 4 ] [ 5 ] The more concentrated the oxygen, the faster the wood burns, and the more intense the flame. This test is not specific for oxygen, but will react similarly for any oxidising gas (such as nitrous oxide ) that supports the combustion of the splint. | https://en.wikipedia.org/wiki/Glowing_splint_test |
Glowmatography [ 1 ] is a laboratory technique for the separation of dyes present in solutions contained in glow sticks . The chemical components of such solutions can be chromatographically separated into polar and nonpolar components. Developed as a laboratory class experiment, it can be used to demonstrate chemistry concepts of polarity, chemical kinetics , and chemiluminescence . [ 2 ]
In the chromatography of a glow stick solution, a piece of chalk , a highly polar substance, is used as the stationary phase while comparatively less-polar solvents like acetone and 91% isopropyl alcohol can be used as the mobile phase . [ 1 ] Chalk is made up of calcium carbonate (CaCO 3 ) or calcium sulfate (CaSO 4 ), [ 3 ] and therefore contains ions. This allows it to attract other ions and polar molecules , but not nonpolar molecules . As a result, ionic and more-polar dyes would be attracted to the stationary phase and move relatively slowly or a fairly small distance, while less polar dyes would migrate further as the mobile phase wicks up the chalk. [ 4 ] This then allows for the separation of dyes.
This experiment can be conducted with glow sticks, chalks, and solutions of acetone or isopropyl alcohol.
Drops of glowing fluid from a glow stick are added to a chalk so that a band is created halfway through it. The chalk is then placed vertically into a beaker filled with a small amount of acetone or alcohol - ensuring the surface of the solvent is below the dye band. The liquid is then allowed to travel up the chalk; polar dyes would tend to stick to the chalk and not travel significantly while non-polar dyes would travel up with the solvent. Once it travels almost to the top of the chalk, it is removed from the beaker. The chalk chromatogram , with separation of colours, can then be observed in a dark room. [ 2 ]
Additionally, this glomatographic experiment can be done using other materials. For instance, silica gel can be used as the stationary phase together with a solution of nonpolar hexanes acting as the mobile phase. [ 1 ] The polar components would be attracted to the polar silanol (Si-OH) groups on the surface of the silica gel, and the nonpolar components would travel further with the hexanes. [ 1 ] Further, dyes in glow sticks can also be extracted using liquid carbon dioxide (CO 2 ) as an environmentally friendly or green solvent . In this case, non polar dyes would dissolve in the liquid CO 2 and other dyes would be attracted to cotton. [ 5 ] | https://en.wikipedia.org/wiki/Glowmatography |
A glowworm [ 1 ] is a luminous trail of a tiny meteor , occasionally visible in the night sky during a meteor shower .
The centimeter-sized comet pieces can produce hundreds of fireballs or more each hour. In some cases, particularly during the Leonids , the fireballs make bright trails that can stay up for 10 to 15 minutes, according to astronomers .
This astronomy -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glowworm_(astronomy) |
Glucagon-like peptide-2 ( GLP-2 ) is a 33 amino acid peptide with the sequence HADGSFSDEMNTILDNLAARDFINWLIQTKITD (see Proteinogenic amino acid ) in humans. GLP-2 is created by specific post-translational proteolytic cleavage of proglucagon in a process that also liberates the related glucagon-like peptide-1 (GLP-1). GLP-2 is produced by the intestinal endocrine L cell and by various neurons in the central nervous system . Intestinal GLP-2 is co-secreted along with GLP-1 upon nutrient ingestion.
When externally administered, GLP-2 produces a number of effects in humans and rodents , including intestinal growth, enhancement of intestinal function, reduction in bone breakdown and neuroprotection. GLP-2 may act in an endocrine fashion to link intestinal growth and metabolism with nutrient intake. GLP-2 and related analogs may be treatments for short bowel syndrome , Crohn's disease , osteoporosis and as adjuvant therapy during cancer chemotherapy .
GLP-2 has an antidepressant effect in a mouse model of depression when delivered via intracerebroventricular injection . However, a GLP-2 derivative (PAS-CPP-GLP-2) was shown to be efficiently delivered to the brain intranasally , with similar efficacy. [ 1 ] | https://en.wikipedia.org/wiki/Glucagon-like_peptide-2 |
Glucocerebroside (also called glucosylceramide ) is any of the cerebrosides in which the monosaccharide head group is glucose .
Research conducted on glucocerebrosides has shown that glucocerebrosides help support cellular functions in humans, such as signaling pathways as well as being possibly linked to diseases. Certain symptoms of diseases such as Gaucher's and Parkinson's disease have been linked to abnormal changes in glucocerebroside metabolism, such as changes in glucocerebroside levels and regulation. Researchers have also started to study the role of glucocerebrosides in cancer. [ 1 ]
In Gaucher's disease , the enzyme glucocerebrosidase is nonfunctional and cannot break down glucocerebroside into glucose and ceramide in the lysosome. [ 2 ] Affected macrophages , called Gaucher cells, have a distinct appearance similar to "wrinkled tissue paper" under light microscopy , because the substrates build-up within the lysosome. [ 3 ]
In 2019, research conducted by Lee et al., shows that glucocerebrosides impaired the formation of new blood vessels (angiogenesis) by decreasing the activity of Runx2 transcription factor, which leads to less vascular endothelial growth factor to be made. [ 4 ]
In 2023, research conducted by Russo et al., shows that increased levels of glucocerebroside can cause inflammation in dopamine-producing cells of the brain, which is usually seen in age-related diseases. The increased glucocerebroside levels is caused by a change in the SATB1-MIR22-GBA pathway, which leads to damage itolysosome and mitochondria lfunction. This damage is seen as a possible link to brain inflammation associated with Parkinson's disease . [ 5 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glucocerebroside |
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The glucocorticoid receptor ( GR or GCR ) also known by its gene name NR3C1 ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol .
The GR is expressed in almost every cell in the body and regulates genes controlling the development , metabolism , inflammation , and immune response . Because the receptor gene is expressed in several forms, it has many different ( pleiotropic ) effects in different parts of the body and in the context of different diseases.
GR is a steroid receptor and thus its cannonical action is similar to other steroid receptors. [ 5 ] [ 6 ] The unbound receptor resides in the cytosol of the cell. When glucocorticoids bind to the receptor, GR translocates to the nucleus of the cell where it acts as a transcription factor . The activated GR complex up-regulates the expression of anti-inflammatory proteins in the nucleus or represses the expression of pro-inflammatory proteins in the cytosol (by preventing the translocation of other transcription factors from the cytosol into the nucleus). [ 6 ]
In humans, the GR protein is encoded by NR3C1 gene which is located on chromosome 5 (5q31). [ 7 ] [ 8 ]
Like the other steroid receptors , [ 9 ] GR is modular in structure [ 10 ] and contains the following domains (labeled A - F ):
In the absence of hormone, the glucocorticoid receptor (GR) resides in the cytosol complexed with a variety of proteins including heat shock protein 90 ( hsp90 ), the heat shock protein 70 ( hsp70 ) and the protein FKBP4 ( FK506 -binding protein 4). [ 11 ] The endogenous glucocorticoid hormone cortisol diffuses through the cell membrane into the cytoplasm and binds to the glucocorticoid receptor (GR) resulting in the release of the heat shock proteins. The resulting activated form GR has two principal mechanisms of action, transactivation, and transrepression, [ 12 ] [ 13 ] described below.
A direct mechanism of action involves homodimerization of the receptor, translocation via active transport into the nucleus , and binding to specific DNA response elements activating gene transcription . This mechanism of action is referred to as transactivation . The biological response depends on the cell type. [ citation needed ]
In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes. [ 14 ] However activated GR can complex with these other transcription factors and prevent them from binding their target genes and hence repress the expression of genes that are normally upregulated by NF-κB or AP-1. This indirect mechanism of action is referred to as transrepression . [ citation needed ] GR transrepression via NF-κB and AP-1 is restricted only to certain cell types, and is not considered the universal mechanism for IκBα repression. [ 15 ] [ 16 ]
The GR is abnormal in familial glucocorticoid resistance . [ 17 ]
In central nervous system structures, the glucocorticoid receptor is gaining interest as a novel representative of neuroendocrine integration, functioning as a major component of endocrine influence — specifically the stress response — upon the brain. The receptor is now implicated in both short and long-term adaptations seen in response to stressors and may be critical to the understanding of psychological disorders, including some or all subtypes of depression and post-traumatic stress disorder ( PTSD ). [ 18 ] Indeed, long-standing observations such as the mood dysregulations typical of Cushing's disease demonstrate the role of corticosteroids in regulating psychologic state; recent advances have demonstrated interactions with norepinephrine and serotonin at the neural level. [ 19 ] [ 20 ]
In preeclampsia (a hypertensive disorder commonly occurring in pregnant women), the level of a miRNA sequence possibly targeting this protein is elevated in the blood of the mother. Rather, the placenta elevates the level of exosomes containing this miRNA, which can result in inhibition of translation of molecule. Clinical significance of this information is not yet clarified. [ 21 ]
Dexamethasone and other corticosteroids are agonists , while mifepristone and ketoconazole are antagonists of GR. Anabolic steroids also prevent cortisol from binding to the glucocorticoid receptor.
Glucocorticoid receptor has been shown to interact with: | https://en.wikipedia.org/wiki/Glucocorticoid_receptor |
Gluconeogenesis ( GNG ) is a metabolic pathway that results in the biosynthesis of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. [ 1 ] In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys . It is one of two primary mechanisms – the other being degradation of glycogen ( glycogenolysis ) – used by humans and many other animals to maintain blood sugar levels , avoiding low levels ( hypoglycemia ). [ 2 ] In ruminants , because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. [ 3 ] In many other animals, the process occurs during periods of fasting , starvation , low-carbohydrate diets , or intense exercise .
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins , these substrates include glucogenic amino acids (although not ketogenic amino acids ); from breakdown of lipids (such as triglycerides ), they include glycerol , odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism that includes lactate from the Cori cycle . Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. [ 4 ] Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting. [ 5 ]
The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or GTP , effectively making the process exergonic . For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation . [ 6 ]
In humans the main gluconeogenic precursors are lactate , glycerol (which is a part of the triglyceride molecule), alanine and glutamine . Altogether, they account for over 90% of the overall gluconeogenesis. [ 8 ] Other glucogenic amino acids and all citric acid cycle intermediates (through conversion to oxaloacetate ) can also function as substrates for gluconeogenesis. [ 9 ] Generally, human consumption of gluconeogenic substrates in food does not result in increased gluconeogenesis. [ 10 ]
In ruminants , propionate is the principal gluconeogenic substrate. [ 3 ] [ 11 ] In nonruminants, including human beings, propionate arises from the β-oxidation of odd-chain and branched-chain fatty acids, and is a (relatively minor) substrate for gluconeogenesis. [ 12 ] [ 13 ]
Lactate is transported back to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate dehydrogenase . Pyruvate, the first designated substrate of the gluconeogenic pathway, can then be used to generate glucose. [ 9 ] Transamination or deamination of amino acids facilitates entering of their carbon skeleton into the cycle directly (as pyruvate or oxaloacetate), or indirectly via the citric acid cycle. The contribution of Cori cycle lactate to overall glucose production increases with fasting duration. [ 14 ] Specifically, after 12, 20, and 40 hours of fasting by human volunteers, the contribution of Cori cycle lactate to gluconeogenesis was 41%, 71%, and 92%, respectively. [ 14 ]
Whether even-chain fatty acids can be converted into glucose in animals has been a longstanding question in biochemistry. [ 15 ] Odd-chain fatty acids can be oxidized to yield acetyl-CoA and propionyl-CoA , the latter serving as a precursor to succinyl-CoA , which can be converted to oxaloacetate and enter into gluconeogenesis. In contrast, even-chain fatty acids are oxidized to yield only acetyl-CoA, whose entry into gluconeogenesis requires the presence of a glyoxylate cycle (also known as glyoxylate shunt) to produce four-carbon dicarboxylic acid precursors. [ 9 ] The glyoxylate shunt comprises two enzymes, malate synthase and isocitrate lyase, and is present in fungi, plants, and bacteria. Despite some reports of glyoxylate shunt enzymatic activities detected in animal tissues, genes encoding both enzymatic functions have only been found in nematodes , in which they exist as a single bi-functional enzyme. [ 16 ] [ 17 ] Genes coding for malate synthase alone (but not isocitrate lyase) have been identified in other animals including arthropods , echinoderms , and even some vertebrates . Mammals found to possess the malate synthase gene include monotremes ( platypus ) and marsupials ( opossum ), but not placental mammals . [ 17 ]
The existence of the glyoxylate cycle in humans has not been established, and it is widely held that fatty acids cannot be converted to glucose in humans directly. Carbon-14 has been shown to end up in glucose when it is supplied in fatty acids, [ 18 ] but this can be expected from the incorporation of labelled atoms derived from acetyl-CoA into citric acid cycle intermediates which are interchangeable with those derived from other physiological sources, such as glucogenic amino acids. [ 15 ] In the absence of other glucogenic sources, the 2-carbon acetyl-CoA derived from the oxidation of fatty acids cannot produce a net yield of glucose via the citric acid cycle , since an equivalent two carbon atoms are released as carbon dioxide during the cycle. During ketosis , however, acetyl-CoA from fatty acids yields ketone bodies , including acetone , and up to ~60% of acetone may be oxidized in the liver to the pyruvate precursors acetol and methylglyoxal . [ 19 ] [ 4 ] Thus ketone bodies derived from fatty acids could account for up to 11% [ citation needed ] of gluconeogenesis during starvation. Catabolism of fatty acids also produces energy in the form of ATP that is necessary for the gluconeogenesis pathway.
In mammals, gluconeogenesis has been believed to be restricted to the liver, [ 20 ] the kidney, [ 20 ] the intestine, [ 21 ] and muscle, [ 22 ] but recent evidence indicates gluconeogenesis occurring in astrocytes of the brain. [ 23 ] These organs use somewhat different gluconeogenic precursors. The liver preferentially uses lactate, glycerol, and glucogenic amino acids (especially alanine ) while the kidney preferentially uses lactate, glutamine and glycerol. [ 24 ] [ 8 ] Lactate from the Cori cycle is quantitatively the largest source of substrate for gluconeogenesis, especially for the kidney. [ 8 ] The liver uses both glycogenolysis and gluconeogenesis to produce glucose, whereas the kidney only uses gluconeogenesis. [ 8 ] After a meal, the liver shifts to glycogen synthesis , whereas the kidney increases gluconeogenesis. [ 10 ] The intestine uses mostly glutamine and glycerol. [ 21 ]
Propionate is the principal substrate for gluconeogenesis in the ruminant liver, and the ruminant liver may make increased use of gluconeogenic amino acids (e.g., alanine) when glucose demand is increased. [ 25 ] The capacity of liver cells to use lactate for gluconeogenesis declines from the preruminant stage to the ruminant stage in calves and lambs. [ 26 ] In sheep kidney tissue, very high rates of gluconeogenesis from propionate have been observed. [ 26 ]
In all species, the formation of oxaloacetate from pyruvate and TCA cycle intermediates is restricted to the mitochondrion, and the enzymes that convert Phosphoenolpyruvic acid (PEP) to glucose-6-phosphate are found in the cytosol. [ 27 ] The location of the enzyme that links these two parts of gluconeogenesis by converting oxaloacetate to PEP – PEP carboxykinase (PEPCK) – is variable by species: it can be found entirely within the mitochondria , entirely within the cytosol , or dispersed evenly between the two, as it is in humans. [ 27 ] Transport of PEP across the mitochondrial membrane is accomplished by dedicated transport proteins; however no such proteins exist for oxaloacetate . [ 27 ] Therefore, in species that lack intra-mitochondrial PEPCK, oxaloacetate must be converted into malate or aspartate , exported from the mitochondrion , and converted back into oxaloacetate in order to allow gluconeogenesis to continue. [ 27 ]
Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway will begin in either the liver or kidney, in the mitochondria or cytoplasm of those cells, this being dependent on the substrate being used. Many of the reactions are the reverse of steps found in glycolysis . [ citation needed ]
While most steps in gluconeogenesis are the reverse of those found in glycolysis , three regulated and strongly endergonic reactions are replaced with more kinetically favorable reactions. Hexokinase / glucokinase , phosphofructokinase , and pyruvate kinase enzymes of glycolysis are replaced with glucose-6-phosphatase , fructose-1,6-bisphosphatase , and PEP carboxykinase /pyruvate carboxylase. These enzymes are typically regulated by similar molecules, but with opposite results. For example, acetyl CoA and citrate activate gluconeogenesis enzymes (pyruvate carboxylase and fructose-1,6-bisphosphatase, respectively), while at the same time inhibiting the glycolytic enzyme pyruvate kinase . This system of reciprocal control allow glycolysis and gluconeogenesis to inhibit each other and prevents a futile cycle of synthesizing glucose to only break it down. Pyruvate kinase can be also bypassed by 86 pathways [ 28 ] not related to gluconeogenesis, for the purpose of forming pyruvate and subsequently lactate; some of these pathways use carbon atoms originated from glucose.
The majority of the enzymes responsible for gluconeogenesis are found in the cytosol ; the exceptions are mitochondrial pyruvate carboxylase and, in animals, phosphoenolpyruvate carboxykinase . The latter exists as an isozyme located in both the mitochondrion and the cytosol . [ 29 ] The rate of gluconeogenesis is ultimately controlled by the action of a key enzyme, fructose-1,6-bisphosphatase , which is also regulated through signal transduction by cAMP and its phosphorylation.
Global control of gluconeogenesis is mediated by glucagon ( released when blood glucose is low ); it triggers phosphorylation of enzymes and regulatory proteins by Protein Kinase A (a cyclic AMP regulated kinase) resulting in inhibition of glycolysis and stimulation of gluconeogenesis. Insulin counteracts glucagon by inhibiting gluconeogenesis. Type 2 diabetes is marked by excess glucagon and insulin resistance from the body. [ 30 ] Insulin can no longer inhibit the gene expression of enzymes such as PEPCK which leads to increased levels of hyperglycemia in the body. [ 31 ] The anti-diabetic drug metformin reduces blood glucose primarily through inhibition of gluconeogenesis, overcoming the failure of insulin to inhibit gluconeogenesis due to insulin resistance. [ 32 ]
Studies have shown that the absence of hepatic glucose production has no major effect on the control of fasting plasma glucose concentration. Compensatory induction of gluconeogenesis occurs in the kidneys and intestine, driven by glucagon , glucocorticoids , and acidosis. [ 33 ]
In the liver, the FOX protein FOXO6 normally promotes gluconeogenesis in the fasted state, but insulin blocks FOXO6 upon feeding. [ 34 ] In a condition of insulin resistance , insulin fails to block FOXO6 resulting in continued gluconeogenesis even upon feeding, resulting in high blood glucose ( hyperglycemia ). [ 34 ]
Insulin resistance is a common feature of metabolic syndrome and type 2 diabetes . For this reason, gluconeogenesis is a target of therapy for type 2 diabetes, such as the antidiabetic drug metformin , which inhibits gluconeogenic glucose formation, and stimulates glucose uptake by cells. [ 35 ]
Gluconeogenesis is considered one of the most ancient anabolic pathways and is likely to have been exhibited in the last universal common ancestor . [ 36 ] Rafael F. Say and Georg Fuchs stated in 2010 that "all archaeal groups as well as the deeply branching bacterial lineages contain a bifunctional fructose 1,6-bisphosphate (FBP) aldolase/phosphatase with both FBP aldolase and FBP phosphatase activity. This enzyme is missing in most other Bacteria and in Eukaryota, and is heat-stabile even in mesophilic marine Crenarchaeota". It is proposed that fructose 1,6-bisphosphate aldolase/phosphatase was an ancestral gluconeogenic enzyme and had preceded glycolysis. [ 37 ] However, a prebiotic glycolysis would follow the same chemical mechanisms as gluconeogenesis, due to microscopic reversibility, and in this view would have occurred at the same time. Fructose 1,6-bisphosphate is shown to be nonenzymatically synthesized within a freezing solution. [ 38 ] The synthesis is accelerated in the presence of amino acids such as glycine and lysine. Some of the other reactions of gluconeogenesis can also proceed nonenzymatically. [ 39 ] Such chemistry could have occurred in hydrothermal environments, including temperature gradients and cycling of freezing and thawing. Mineral surfaces might have played a role in the phosphorylation of metabolic intermediates from gluconeogenesis and have to been shown to produce tetrose, hexose phosphates, and pentose from formaldehyde , glyceraldehyde, and glycolaldehyde. [ 40 ] | https://en.wikipedia.org/wiki/Gluconeogenesis |
Glucose is a sugar with the molecular formula C 6 H 12 O 6 , which is often abbreviated as Glc . [ 4 ] It is overall the most abundant monosaccharide , [ 5 ] a subcategory of carbohydrates . It is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight. It is used by plants to make cellulose , the most abundant carbohydrate in the world, for use in cell walls , and by all living organisms to make adenosine triphosphate (ATP), which is used by the cell as energy. [ 6 ] [ 7 ] [ 8 ]
In energy metabolism , glucose is the most important source of energy in all organisms . Glucose for metabolism is stored as a polymer , in plants mainly as amylose and amylopectin , and in animals as glycogen . Glucose circulates in the blood of animals as blood sugar . [ 6 ] [ 8 ] The naturally occurring form is d -glucose, while its stereoisomer l -glucose is produced synthetically in comparatively small amounts and is less biologically active. [ 8 ] Glucose is a monosaccharide containing six carbon atoms and an aldehyde group, and is therefore an aldohexose . The glucose molecule can exist in an open-chain (acyclic) as well as ring (cyclic) form. Glucose is naturally occurring and is found in its free state in fruits and other parts of plants. In animals, it is released from the breakdown of glycogen in a process known as glycogenolysis .
Glucose, as intravenous sugar solution , is on the World Health Organization's List of Essential Medicines . [ 9 ] It is also on the list in combination with sodium chloride (table salt). [ 9 ]
The name glucose is derived from Ancient Greek γλεῦκος ( gleûkos ) 'wine, must', from γλυκύς ( glykýs ) 'sweet'. [ 10 ] [ 11 ] The suffix -ose is a chemical classifier denoting a sugar.
Glucose was first isolated from raisins in 1747 by the German chemist Andreas Marggraf . [ 12 ] [ 13 ] Glucose was discovered in grapes by another German chemist – Johann Tobias Lowitz – in 1792, and distinguished as being different from cane sugar ( sucrose ). Glucose is the term coined by Jean Baptiste Dumas in 1838, which has prevailed in the chemical literature. Friedrich August Kekulé proposed the term dextrose (from the Latin dexter , meaning "right"), because in aqueous solution of glucose, the plane of linearly polarized light is turned to the right. In contrast, l-fructose (usually referred to as d -fructose) (a ketohexose) and l-glucose ( l -glucose) turn linearly polarized light to the left. The earlier notation according to the rotation of the plane of linearly polarized light ( d and l -nomenclature) was later abandoned in favor of the d - and l -notation , which refers to the absolute configuration of the asymmetric center farthest from the carbonyl group, and in concordance with the configuration of d - or l -glyceraldehyde. [ 14 ] [ 15 ]
Since glucose is a basic necessity of many organisms, a correct understanding of its chemical makeup and structure contributed greatly to a general advancement in organic chemistry . This understanding occurred largely as a result of the investigations of Emil Fischer , a German chemist who received the 1902 Nobel Prize in Chemistry for his findings. [ 16 ] The synthesis of glucose established the structure of organic material and consequently formed the first definitive validation of Jacobus Henricus van 't Hoff 's theories of chemical kinetics and the arrangements of chemical bonds in carbon-bearing molecules. [ 17 ] Between 1891 and 1894, Fischer established the stereochemical configuration of all the known sugars and correctly predicted the possible isomers , applying Van 't Hoff equation of asymmetrical carbon atoms. The names initially referred to the natural substances. Their enantiomers were given the same name with the introduction of systematic nomenclatures, taking into account absolute stereochemistry (e.g. Fischer nomenclature , d / l nomenclature).
For the discovery of the metabolism of glucose Otto Meyerhof received the Nobel Prize in Physiology or Medicine in 1922. [ 18 ] Hans von Euler-Chelpin was awarded the Nobel Prize in Chemistry along with Arthur Harden in 1929 for their "research on the fermentation of sugar and their share of enzymes in this process". [ 19 ] [ 20 ] In 1947, Bernardo Houssay (for his discovery of the role of the pituitary gland in the metabolism of glucose and the derived carbohydrates) as well as Carl and Gerty Cori (for their discovery of the conversion of glycogen from glucose) received the Nobel Prize in Physiology or Medicine. [ 21 ] [ 22 ] [ 23 ] In 1970, Luis Leloir was awarded the Nobel Prize in Chemistry for the discovery of glucose-derived sugar nucleotides in the biosynthesis of carbohydrates. [ 24 ]
Glucose forms white or colorless solids that are highly soluble in water and acetic acid but poorly soluble in methanol and ethanol . They melt at 146 °C (295 °F) ( α ) and 150 °C (302 °F) ( beta ), decompose starting at 188 °C (370 °F) with release of various volatile products, ultimately leaving a residue of carbon . [ 25 ] Glucose has a pKa value of 12.16 at 25 °C (77 °F) in water. [ 26 ]
With six carbon atoms, it is classed as a hexose , a subcategory of the monosaccharides . d -Glucose is one of the sixteen aldohexose stereoisomers . The d - isomer , d -glucose, also known as dextrose, occurs widely in nature, but the l -isomer, l -glucose , does not. Glucose can be obtained by hydrolysis of carbohydrates such as milk sugar ( lactose ), cane sugar (sucrose), maltose , cellulose , glycogen , etc. Dextrose is commonly commercially manufactured from starches , such as corn starch in the US and Japan, from potato and wheat starch in Europe, and from tapioca starch in tropical areas. [ 27 ] The manufacturing process uses hydrolysis via pressurized steaming at controlled pH in a jet followed by further enzymatic depolymerization. [ 28 ] Unbonded glucose is one of the main ingredients of honey . [ 29 ] [ 30 ] [ 31 ] [ 32 ] [ 33 ]
The term dextrose is often used in a clinical (related to patient's health status) or nutritional context (related to dietary intake, such as food labels or dietary guidelines), while "glucose" is used in a biological or physiological context (chemical processes and molecular interactions), [ 34 ] [ 35 ] [ 36 ] [ 37 ] but both terms refer to the same molecule, specifically D-glucose. [ 36 ] [ 38 ]
Dextrose monohydrate is the hydrated form of D-glucose, meaning that it is a glucose molecule with an additional water molecule attached. [ 39 ] Its chemical formula is C 6 H 12 O 6 · H 2 O . [ 39 ] [ 40 ] Dextrose monohydrate is also called hydrated D-glucose , and commonly manufactured from plant starches. [ 39 ] [ 41 ] Dextrose monohydrate is utilized as the predominant type of dextrose in food applications, such as beverage mixes—it is a common form of glucose widely used as a nutrition supplement in production of foodstuffs. Dextrose monohydrate is primarily consumed in North America as a corn syrup or high-fructose corn syrup . [ 36 ]
Anhydrous dextrose , on the other hand, is glucose that does not have any water molecules attached to it. [ 41 ] [ 42 ] Anhydrous chemical substances are commonly produced by eliminating water from a hydrated substance through methods such as heating or drying up (desiccation). [ 43 ] [ 44 ] [ 45 ] Dextrose monohydrate can be dehydrated to anhydrous dextrose in industrial setting. [ 46 ] [ 47 ] Dextrose monohydrate is composed of approximately 9.5% water by mass; through the process of dehydration, this water content is eliminated to yield anhydrous (dry) dextrose. [ 41 ]
Anhydrous dextrose has the chemical formula C 6 H 12 O 6 , without any water molecule attached which is the same as glucose. [ 39 ] Anhydrous dextrose on open air tends to absorb moisture and transform to the monohydrate, and it is more expensive to produce. [ 41 ] Anhydrous dextrose (anhydrous D-glucose) has increased stability and increased shelf life, [ 44 ] has medical applications, such as in oral glucose tolerance test . [ 48 ]
Whereas molecular weight (molar mass) for D-glucose monohydrate is 198.17 g/mol, [ 49 ] [ 50 ] that for anhydrous D-glucose is 180.16 g/mol [ 51 ] [ 52 ] [ 53 ] The density of these two forms of glucose is also different. [ specify ]
In terms of chemical structure, glucose is a monosaccharide, that is, a simple sugar. Glucose contains six carbon atoms and an aldehyde group , and is therefore an aldohexose . The glucose molecule can exist in an open-chain (acyclic) as well as ring (cyclic) form—due to the presence of alcohol and aldehyde or ketone functional groups, the form having the straight chain can easily convert into a chair-like hemiacetal ring structure commonly found in carbohydrates. [ 54 ]
Glucose is present in solid form as a monohydrate with a closed pyran ring (α-D-glucopyranose monohydrate, sometimes known less precisely by dextrose hydrate). In aqueous solution, on the other hand, a small proportion of glucose can be found in an open-chain configuration while remaining predominantly as α- or β- pyranose , which interconvert. From aqueous solutions, the three known forms can be crystallized: α-glucopyranose, β-glucopyranose and α-glucopyranose monohydrate. [ 55 ] Glucose is a building block of the disaccharides lactose and sucrose (cane or beet sugar), of oligosaccharides such as raffinose and of polysaccharides such as starch , amylopectin , glycogen , and cellulose . [ 8 ] [ 56 ] The glass transition temperature of glucose is 31 °C (88 °F) and the Gordon–Taylor constant (an experimentally determined constant for the prediction of the glass transition temperature for different mass fractions of a mixture of two substances) [ 56 ] is 4.5. [ 57 ]
A open-chain form of glucose makes up less than 0.02% of the glucose molecules in an aqueous solution at equilibrium. [ 58 ] The rest is one of two cyclic hemiacetal forms. In its open-chain form, the glucose molecule has an open (as opposed to cyclic ) unbranched backbone of six carbon atoms, where C-1 is part of an aldehyde group H(C=O)− . Therefore, glucose is also classified as an aldose , or an aldohexose . The aldehyde group makes glucose a reducing sugar giving a positive reaction with the Fehling test .
In solutions, the open-chain form of glucose (either " D -" or " L -") exists in equilibrium with several cyclic isomers , each containing a ring of carbons closed by one oxygen atom. In aqueous solution, however, more than 99% of glucose molecules exist as pyranose forms. The open-chain form is limited to about 0.25%, and furanose forms exist in negligible amounts. The terms "glucose" and " D -glucose" are generally used for these cyclic forms as well. The ring arises from the open-chain form by an intramolecular nucleophilic addition reaction between the aldehyde group (at C-1) and either the C-4 or C-5 hydroxyl group, forming a hemiacetal linkage, −C(OH)H−O− .
The reaction between C-1 and C-5 yields a six-membered heterocyclic system called a pyranose, which is a monosaccharide sugar (hence "-ose") containing a derivatised pyran skeleton. The (much rarer) reaction between C-1 and C-4 yields a five-membered furanose ring, named after the cyclic ether furan . In either case, each carbon in the ring has one hydrogen and one hydroxyl attached, except for the last carbon (C-4 or C-5) where the hydroxyl is replaced by the remainder of the open molecule (which is −(C(CH 2 OH)HOH)−H or −(CHOH)−H respectively).
The ring-closing reaction can give two products, denoted "α-" and "β-". When a glucopyranose molecule is drawn in the Haworth projection , the designation "α-" means that the hydroxyl group attached to C-1 and the −CH 2 OH group at C-5 lies on opposite sides of the ring's plane (a trans arrangement), while "β-" means that they are on the same side of the plane (a cis arrangement). Therefore, the open-chain isomer D -glucose gives rise to four distinct cyclic isomers: α- D -glucopyranose, β- D -glucopyranose, α- D -glucofuranose, and β- D -glucofuranose. These five structures exist in equilibrium and interconvert, and the interconversion is much more rapid with acid catalysis .
The other open-chain isomer L -glucose similarly gives rise to four distinct cyclic forms of L -glucose, each the mirror image of the corresponding D -glucose.
The glucopyranose ring (α or β) can assume several non-planar shapes, analogous to the "chair" and "boat" conformations of cyclohexane . Similarly, the glucofuranose ring may assume several shapes, analogous to the "envelope" conformations of cyclopentane .
In the solid state, only the glucopyranose forms are observed.
Some derivatives of glucofuranose, such as 1,2- O -isopropylidene- D -glucofuranose are stable and can be obtained pure as crystalline solids. [ 59 ] [ 60 ] For example, reaction of α-D-glucose with para -tolylboronic acid H 3 C−(C 6 H 4 )−B(OH) 2 reforms the normal pyranose ring to yield the 4-fold ester α-D-glucofuranose-1,2:3,5-bis( p -tolylboronate). [ 61 ]
Mutarotation consists of a temporary reversal of the ring-forming reaction, resulting in the open-chain form, followed by a reforming of the ring. The ring closure step may use a different −OH group than the one recreated by the opening step (thus switching between pyranose and furanose forms), or the new hemiacetal group created on C-1 may have the same or opposite handedness as the original one (thus switching between the α and β forms). Thus, though the open-chain form is barely detectable in solution, it is an essential component of the equilibrium.
The open-chain form is thermodynamically unstable , and it spontaneously isomerizes to the cyclic forms. (Although the ring closure reaction could in theory create four- or three-atom rings, these would be highly strained, and are not observed in practice.) In solutions at room temperature , the four cyclic isomers interconvert over a time scale of hours, in a process called mutarotation . [ 62 ] Starting from any proportions, the mixture converges to a stable ratio of α:β 36:64. The ratio would be α:β 11:89 if it were not for the influence of the anomeric effect . [ 63 ] Mutarotation is considerably slower at temperatures close to 0 °C (32 °F).
Whether in water or the solid form, d -(+)-glucose is dextrorotatory , meaning it will rotate the direction of polarized light clockwise as seen looking toward the light source. The effect is due to the chirality of the molecules, and indeed the mirror-image isomer, l -(−)-glucose, is levorotatory (rotates polarized light counterclockwise) by the same amount. The strength of the effect is different for each of the five tautomers .
The d - prefix does not refer directly to the optical properties of the compound. It indicates that the C-5 chiral centre has the same handedness as that of d -glyceraldehyde (which was so labelled because it is dextrorotatory). The fact that d -glucose is dextrorotatory is a combined effect of its four chiral centres, not just of C-5; some of the other d -aldohexoses are levorotatory.
The conversion between the two anomers can be observed in a polarimeter since pure α- d -glucose has a specific rotation angle of +112.2° mL/(dm·g), pure β- d -glucose of +17.5° mL/(dm·g). [ 64 ] When equilibrium has been reached after a certain time due to mutarotation, the angle of rotation is +52.7° mL/(dm·g). [ 64 ] By adding acid or base, this transformation is much accelerated. The equilibration takes place via the open-chain aldehyde form.
In dilute sodium hydroxide or other dilute bases, the monosaccharides mannose , glucose and fructose interconvert (via a Lobry de Bruyn–Alberda–Van Ekenstein transformation ), so that a balance between these isomers is formed. This reaction proceeds via an enediol :
Glucose is the most abundant monosaccharide. Glucose is also the most widely used aldohexose in most living organisms. One possible explanation for this is that glucose has a lower tendency than other aldohexoses to react nonspecifically with the amine groups of proteins . [ 65 ] This reaction— glycation —impairs or destroys the function of many proteins, [ 65 ] e.g. in glycated hemoglobin . Glucose's low rate of glycation can be attributed to its having a more stable cyclic form compared to other aldohexoses, which means it spends less time than they do in its reactive open-chain form . [ 65 ] The reason for glucose having the most stable cyclic form of all the aldohexoses is that its hydroxy groups (with the exception of the hydroxy group on the anomeric carbon of d -glucose) are in the equatorial position . Presumably, glucose is the most abundant natural monosaccharide because it is less glycated with proteins than other monosaccharides. [ 65 ] [ 66 ] Another hypothesis is that glucose, being the only d -aldohexose that has all five hydroxy substituents in the equatorial position in the form of β- d -glucose, is more readily accessible to chemical reactions, [ 67 ] : 194, 199 for example, for esterification [ 68 ] : 363 or acetal formation. [ 69 ] For this reason, d -glucose is also a highly preferred building block in natural polysaccharides (glycans). Polysaccharides that are composed solely of glucose are termed glucans .
Glucose is produced by plants through photosynthesis using sunlight, [ 70 ] [ 71 ] water and carbon dioxide and can be used by all living organisms as an energy and carbon source. However, most glucose does not occur in its free form, but in the form of its polymers, i.e. lactose, sucrose, starch and others which are energy reserve substances, and cellulose and chitin , which are components of the cell wall in plants or fungi and arthropods , respectively. These polymers, when consumed by animals, fungi and bacteria, are degraded to glucose using enzymes. All animals are also able to produce glucose themselves from certain precursors as the need arises. Neurons , cells of the renal medulla and erythrocytes depend on glucose for their energy production. [ 71 ] In adult humans, there is about 18 g (0.63 oz) of glucose, [ 72 ] of which about 4 g (0.14 oz) is present in the blood. [ 73 ] Approximately 180–220 g (6.3–7.8 oz) of glucose is produced in the liver of an adult in 24 hours. [ 72 ]
Many of the long-term complications of diabetes (e.g., blindness , kidney failure , and peripheral neuropathy ) are probably due to the glycation of proteins or lipids . [ 74 ] In contrast, enzyme -regulated addition of sugars to protein is called glycosylation and is essential for the function of many proteins. [ 75 ]
Ingested glucose initially binds to the receptor for sweet taste on the tongue in humans. This complex of the proteins T1R2 and T1R3 makes it possible to identify glucose-containing food sources. [ 76 ] [ 77 ] Glucose mainly comes from food—about 300 g (11 oz) per day is produced by conversion of food, [ 77 ] but it is also synthesized from other metabolites in the body's cells. In humans, the breakdown of glucose-containing polysaccharides happens in part already during chewing by means of amylase , which is contained in saliva , as well as by maltase , lactase , and sucrase on the brush border of the small intestine . Glucose is a building block of many carbohydrates and can be split off from them using certain enzymes. Glucosidases , a subgroup of the glycosidases, first catalyze the hydrolysis of long-chain glucose-containing polysaccharides, removing terminal glucose. In turn, disaccharides are mostly degraded by specific glycosidases to glucose. The names of the degrading enzymes are often derived from the particular poly- and disaccharide; inter alia, for the degradation of polysaccharide chains there are amylases (named after amylose, a component of starch), cellulases (named after cellulose), chitinases (named after chitin), and more. Furthermore, for the cleavage of disaccharides, there are maltase, lactase, sucrase, trehalase , and others. In humans, about 70 genes are known that code for glycosidases. They have functions in the digestion and degradation of glycogen, sphingolipids , mucopolysaccharides , and poly( ADP-ribose ). Humans do not produce cellulases, chitinases, or trehalases, but the bacteria in the gut microbiota do.
In order to get into or out of cell membranes of cells and membranes of cell compartments, glucose requires special transport proteins from the major facilitator superfamily . In the small intestine (more precisely, in the jejunum ), [ 78 ] glucose is taken up into the intestinal epithelium with the help of glucose transporters [ 79 ] via a secondary active transport mechanism called sodium ion-glucose symport via sodium/glucose cotransporter 1 (SGLT1). [ 80 ] Further transfer occurs on the basolateral side of the intestinal epithelial cells via the glucose transporter GLUT2 , [ 80 ] as well uptake into liver cells , kidney cells, cells of the islets of Langerhans , neurons , astrocytes , and tanycytes . [ 81 ] Glucose enters the liver via the portal vein and is stored there as a cellular glycogen. [ 82 ] In the liver cell, it is phosphorylated by glucokinase at position 6 to form glucose 6-phosphate , which cannot leave the cell. Glucose 6-phosphatase can convert glucose 6-phosphate back into glucose exclusively in the liver, so the body can maintain a sufficient blood glucose concentration. In other cells, uptake happens by passive transport through one of the 14 GLUT proteins. [ 80 ] In the other cell types, phosphorylation occurs through a hexokinase , whereupon glucose can no longer diffuse out of the cell.
The glucose transporter GLUT1 is produced by most cell types and is of particular importance for nerve cells and pancreatic β-cells . [ 80 ] GLUT3 is highly expressed in nerve cells. [ 80 ] Glucose from the bloodstream is taken up by GLUT4 from muscle cells (of the skeletal muscle [ 83 ] and heart muscle ) and fat cells . [ 84 ] GLUT14 is expressed exclusively in testicles . [ 85 ] Excess glucose is broken down and converted into fatty acids, which are stored as triglycerides . In the kidneys , glucose in the urine is absorbed via SGLT1 and SGLT2 in the apical cell membranes and transmitted via GLUT2 in the basolateral cell membranes. [ 86 ] About 90% of kidney glucose reabsorption is via SGLT2 and about 3% via SGLT1. [ 87 ]
In plants and some prokaryotes , glucose is a product of photosynthesis . [ 70 ] Glucose is also formed by the breakdown of polymeric forms of glucose like glycogen (in animals and mushrooms ) or starch (in plants). The cleavage of glycogen is termed glycogenolysis, the cleavage of starch is called starch degradation. [ 88 ]
The metabolic pathway that begins with molecules containing two to four carbon atoms (C) and ends in the glucose molecule containing six carbon atoms is called gluconeogenesis and occurs in all living organisms. The smaller starting materials are the result of other metabolic pathways. Ultimately almost all biomolecules come from the assimilation of carbon dioxide in plants and microbes during photosynthesis. [ 68 ] : 359 The free energy of formation of α- d -glucose is 917.2 kilojoules per mole. [ 68 ] : 59 In humans, gluconeogenesis occurs in the liver and kidney, [ 89 ] but also in other cell types. In the liver about 150 g (5.3 oz) of glycogen are stored, in skeletal muscle about 250 g (8.8 oz). [ 90 ] However, the glucose released in muscle cells upon cleavage of the glycogen can not be delivered to the circulation because glucose is phosphorylated by the hexokinase, and a glucose-6-phosphatase is not expressed to remove the phosphate group. Unlike for glucose, there is no transport protein for glucose-6-phosphate . Gluconeogenesis allows the organism to build up glucose from other metabolites, including lactate or certain amino acids , while consuming energy. The renal tubular cells can also produce glucose.
Glucose also can be found outside of living organisms in the ambient environment. Glucose concentrations in the atmosphere are detected via collection of samples by aircraft and are known to vary from location to location. For example, glucose concentrations in atmospheric air from inland China range from 0.8 to 20.1 pg/L, whereas east coastal China glucose concentrations range from 10.3 to 142 pg/L. [ 91 ]
In humans, glucose is metabolized by glycolysis [ 92 ] and the pentose phosphate pathway. [ 93 ] Glycolysis is used by all living organisms, [ 67 ] : 551 [ 94 ] with small variations, and all organisms generate energy from the breakdown of monosaccharides. [ 94 ] In the further course of the metabolism, it can be completely degraded via oxidative decarboxylation , the citric acid cycle (synonym Krebs cycle ) and the respiratory chain to water and carbon dioxide. If there is not enough oxygen available for this, the glucose degradation in animals occurs anaerobic to lactate via lactic acid fermentation and releases much less energy. Muscular lactate enters the liver through the bloodstream in mammals, where gluconeogenesis occurs ( Cori cycle ). With a high supply of glucose, the metabolite acetyl-CoA from the Krebs cycle can also be used for fatty acid synthesis . [ 95 ] Glucose is also used to replenish the body's glycogen stores, which are mainly found in liver and skeletal muscle. These processes are hormonally regulated.
In other living organisms, other forms of fermentation can occur. The bacterium Escherichia coli can grow on nutrient media containing glucose as the sole carbon source. [ 68 ] : 59 In some bacteria and, in modified form, also in archaea, glucose is degraded via the Entner-Doudoroff pathway . [ 96 ] With glucose, a mechanism for gene regulation was discovered in E. coli , the catabolite repression (formerly known as glucose effect ). [ 97 ]
Use of glucose as an energy source in cells is by either aerobic respiration, anaerobic respiration, or fermentation. [ 98 ] The first step of glycolysis is the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate . The main reason for the immediate phosphorylation of glucose is to prevent its diffusion out of the cell as the charged phosphate group prevents glucose 6-phosphate from easily crossing the cell membrane . [ 98 ] Furthermore, addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis. [ 99 ]
In anaerobic respiration, one glucose molecule produces a net gain of two ATP molecules (four ATP molecules are produced during glycolysis through substrate-level phosphorylation, but two are required by enzymes used during the process). [ 100 ] In aerobic respiration, a molecule of glucose is much more profitable in that a maximum net production of 30 or 32 ATP molecules (depending on the organism) is generated. [ 101 ]
Click on genes, proteins and metabolites below to link to respective articles. [ § 1 ]
Tumor cells often grow comparatively quickly and consume an above-average amount of glucose by glycolysis, [ 102 ] which leads to the formation of lactate, the end product of fermentation in mammals, even in the presence of oxygen. This is called the Warburg effect . For the increased uptake of glucose in tumors various SGLT and GLUT are overly produced. [ 103 ] [ 104 ]
In yeast , ethanol is fermented at high glucose concentrations, even in the presence of oxygen (which normally leads to respiration rather than fermentation). This is called the Crabtree effect .
Glucose can also degrade to form carbon dioxide through abiotic means. This has been demonstrated to occur experimentally via oxidation and hydrolysis at 22 °C and a pH of 2.5. [ 105 ]
Glucose is a ubiquitous fuel in biology . It is used as an energy source in organisms, from bacteria to humans, through either aerobic respiration , anaerobic respiration (in bacteria), or fermentation . Glucose is the human body's key source of energy, through aerobic respiration, providing about 3.75 kilocalories (16 kilojoules ) of food energy per gram. [ 106 ] Breakdown of carbohydrates (e.g., starch) yields mono- and disaccharides , most of which is glucose. Through glycolysis and later in the reactions of the citric acid cycle and oxidative phosphorylation , glucose is oxidized to eventually form carbon dioxide and water, yielding energy mostly in the form of adenosine triphosphate (ATP). The insulin reaction, and other mechanisms, regulate the concentration of glucose in the blood. The physiological caloric value of glucose, depending on the source, is 16.2 kilojoules per gram [ 107 ] or 15.7 kJ/g (3.74 kcal/g). [ 108 ] The high availability of carbohydrates from plant biomass has led to a variety of methods during evolution, especially in microorganisms, to utilize glucose for energy and carbon storage. Differences exist in which end product can no longer be used for energy production. The presence of individual genes, and their gene products, the enzymes, determine which reactions are possible. The metabolic pathway of glycolysis is used by almost all living beings. An essential difference in the use of glycolysis is the recovery of NADPH as a reductant for anabolism that would otherwise have to be generated indirectly. [ 109 ]
Glucose and oxygen supply almost all the energy for the brain , [ 110 ] so its availability influences psychological processes. When glucose is low , psychological processes requiring mental effort (e.g., self-control , effortful decision-making) are impaired. [ 111 ] [ 112 ] [ 113 ] [ 114 ] In the brain, which is dependent on glucose and oxygen as the major source of energy, the glucose concentration is usually 4 to 6 mM (5 mM equals 90 mg/dL), [ 72 ] but decreases to 2 to 3 mM when fasting. [ 115 ] Confusion occurs below 1 mM and coma at lower levels. [ 115 ]
The glucose in the blood is called blood sugar . Blood sugar levels are regulated by glucose-binding nerve cells in the hypothalamus . [ 116 ] In addition, glucose in the brain binds to glucose receptors of the reward system in the nucleus accumbens . [ 116 ] The binding of glucose to the sweet receptor on the tongue induces a release of various hormones of energy metabolism, either through glucose or through other sugars, leading to an increased cellular uptake and lower blood sugar levels. [ 117 ] Artificial sweeteners do not lower blood sugar levels. [ 117 ]
The blood sugar content of a healthy person in the short-time fasting state, e.g. after overnight fasting, is about 70 to 100 mg/dL of blood (4 to 5.5 mM). In blood plasma , the measured values are about 10–15% higher. In addition, the values in the arterial blood are higher than the concentrations in the venous blood since glucose is absorbed into the tissue during the passage of the capillary bed . Also in the capillary blood, which is often used for blood sugar determination, the values are sometimes higher than in the venous blood. The glucose content of the blood is regulated by the hormones insulin , incretin and glucagon . [ 116 ] [ 118 ] Insulin lowers the glucose level, glucagon increases it. [ 72 ] Furthermore, the hormones adrenaline , thyroxine , glucocorticoids , somatotropin and adrenocorticotropin lead to an increase in the glucose level. [ 72 ] There is also a hormone-independent regulation, which is referred to as glucose autoregulation . [ 119 ] After food intake the blood sugar concentration increases. Values over 180 mg/dL in venous whole blood are pathological and are termed hyperglycemia , values below 40 mg/dL are termed hypoglycaemia . [ 120 ] When needed, glucose is released into the bloodstream by glucose-6-phosphatase from glucose-6-phosphate originating from liver and kidney glycogen, thereby regulating the homeostasis of blood glucose concentration. [ 89 ] [ 71 ] In ruminants , the blood glucose concentration is lower (60 mg/dL in cattle and 40 mg/dL in sheep ), because the carbohydrates are converted more by their gut microbiota into short-chain fatty acids . [ 121 ]
Some glucose is converted to lactic acid by astrocytes , which is then utilized as an energy source by brain cells ; some glucose is used by intestinal cells and red blood cells , while the rest reaches the liver , adipose tissue and muscle cells, where it is absorbed and stored as glycogen (under the influence of insulin ). Liver cell glycogen can be converted to glucose and returned to the blood when insulin is low or absent; muscle cell glycogen is not returned to the blood because of a lack of enzymes. In fat cells , glucose is used to power reactions that synthesize some fat types and have other purposes. Glycogen is the body's "glucose energy storage" mechanism, because it is much more "space efficient" and less reactive than glucose itself.
As a result of its importance in human health, glucose is an analyte in glucose tests that are common medical blood tests . [ 122 ] Eating or fasting prior to taking a blood sample has an effect on analyses for glucose in the blood; a high fasting glucose blood sugar level may be a sign of prediabetes or diabetes mellitus . [ 123 ]
The glycemic index is an indicator of the speed of resorption and conversion to blood glucose levels from ingested carbohydrates, measured as the area under the curve of blood glucose levels after consumption in comparison to glucose (glucose is defined as 100). [ 124 ] The clinical importance of the glycemic index is controversial, [ 124 ] [ 125 ] as foods with high fat contents slow the resorption of carbohydrates and lower the glycemic index, e.g. ice cream. [ 125 ] An alternative indicator is the insulin index , [ 126 ] measured as the impact of carbohydrate consumption on the blood insulin levels. The glycemic load is an indicator for the amount of glucose added to blood glucose levels after consumption, based on the glycemic index and the amount of consumed food.
Organisms use glucose as a precursor for the synthesis of several important substances. Starch, cellulose , and glycogen ("animal starch") are common glucose polymers (polysaccharides). Some of these polymers (starch or glycogen) serve as energy stores, while others (cellulose and chitin , which is made from a derivative of glucose) have structural roles. Oligosaccharides of glucose combined with other sugars serve as important energy stores. These include lactose, the predominant sugar in milk, which is a glucose-galactose disaccharide, and sucrose, another disaccharide which is composed of glucose and fructose. Glucose is also added onto certain proteins and lipids in a process called glycosylation . This is often critical for their functioning. The enzymes that join glucose to other molecules usually use phosphorylated glucose to power the formation of the new bond by coupling it with the breaking of the glucose-phosphate bond.
Other than its direct use as a monomer, glucose can be broken down to synthesize a wide variety of other biomolecules. This is important, as glucose serves both as a primary store of energy and as a source of organic carbon. Glucose can be broken down and converted into lipids. It is also a precursor for the synthesis of other important molecules such as vitamin C (ascorbic acid). In living organisms, glucose is converted to several other chemical compounds that are the starting material for various metabolic pathways . Among them, all other monosaccharides [ 127 ] such as fructose (via the polyol pathway ), [ 80 ] mannose (the epimer of glucose at position 2), galactose (the epimer at position 4), fucose, various uronic acids and the amino sugars are produced from glucose. [ 82 ] In addition to the phosphorylation to glucose-6-phosphate, which is part of the glycolysis, glucose can be oxidized during its degradation to glucono-1,5-lactone . Glucose is used in some bacteria as a building block in the trehalose or the dextran biosynthesis and in animals as a building block of glycogen. Glucose can also be converted from bacterial xylose isomerase to fructose. In addition, glucose metabolites produce all nonessential amino acids, sugar alcohols such as mannitol and sorbitol , fatty acids , cholesterol and nucleic acids . [ 127 ] Finally, glucose is used as a building block in the glycosylation of proteins to glycoproteins , glycolipids , peptidoglycans , glycosides and other substances (catalyzed by glycosyltransferases ) and can be cleaved from them by glycosidases .
In addition to its well-known function as a cellular energy source, glucose has been identified as a master regulator of tissue maturation. [ 128 ] A 2025 study by Stanford Medicine uncovered that glucose, in its intact (non-metabolized) form, can bind to various regulatory proteins involved in gene expression. One such protein is IRF6, which alters its conformation upon glucose binding, thereby influencing the expression of genes associated with stem cell differentiation. This regulatory role is independent of glucose’s catabolic function and has been observed across multiple tissue types, including skin, bone, fat, and white blood cells. The research demonstrated that even glucose analogs incapable of metabolism could promote differentiation, suggesting a signaling function for glucose. These findings have potential implications in understanding and treating diseases characterized by impaired differentiation, such as diabetes and certain cancers. [ 129 ]
Diabetes is a metabolic disorder where the body is unable to regulate levels of glucose in the blood either because of a lack of insulin in the body or the failure, by cells in the body, to respond properly to insulin. Each of these situations can be caused by persistently high elevations of blood glucose levels, through pancreatic burnout and insulin resistance . The pancreas is the organ responsible for the secretion of the hormones insulin and glucagon. [ 130 ] Insulin is a hormone that regulates glucose levels, allowing the body's cells to absorb and use glucose. Without it, glucose cannot enter the cell and therefore cannot be used as fuel for the body's functions. [ 131 ] If the pancreas is exposed to persistently high elevations of blood glucose levels, the insulin-producing cells in the pancreas could be damaged, causing a lack of insulin in the body. Insulin resistance occurs when the pancreas tries to produce more and more insulin in response to persistently elevated blood glucose levels. Eventually, the rest of the body becomes resistant to the insulin that the pancreas is producing, thereby requiring more insulin to achieve the same blood glucose-lowering effect, and forcing the pancreas to produce even more insulin to compete with the resistance. This negative spiral contributes to pancreatic burnout, and the disease progression of diabetes.
To monitor the body's response to blood glucose-lowering therapy, glucose levels can be measured. Blood glucose monitoring can be performed by multiple methods, such as the fasting glucose test which measures the level of glucose in the blood after 8 hours of fasting. Another test is the 2-hour glucose tolerance test (GTT) – for this test, the person has a fasting glucose test done, then drinks a 75-gram glucose drink and is retested. This test measures the ability of the person's body to process glucose. Over time the blood glucose levels should decrease as insulin allows it to be taken up by cells and exit the blood stream.
Individuals with diabetes or other conditions that result in low blood sugar often carry small amounts of sugar in various forms. One sugar commonly used is glucose, often in the form of glucose tablets (glucose pressed into a tablet shape sometimes with one or more other ingredients as a binder), hard candy , or sugar packet .
Most dietary carbohydrates contain glucose, either as their only building block (as in the polysaccharides starch and glycogen), or together with another monosaccharide (as in the hetero-polysaccharides sucrose and lactose). [ 132 ] Unbound glucose is one of the main ingredients of honey. Glucose is extremely abundant and has been isolated from a variety of natural sources across the world, including male cones of the coniferous tree Wollemia nobilis in Rome, [ 133 ] the roots of Ilex asprella plants in China, [ 134 ] and straws from rice in California. [ 135 ]
Glucose is produced industrially from starch by enzymatic hydrolysis using glucose amylase or by the use of acids . Enzymatic hydrolysis has largely displaced acid-catalyzed hydrolysis reactions. [ 137 ] The result is glucose syrup (enzymatically with more than 90% glucose in the dry matter) [ 137 ] with an annual worldwide production volume of 20 million tonnes (as of 2011). [ 138 ] This is the reason for the former common name "starch sugar". The amylases most often come from Bacillus licheniformis [ 139 ] or Bacillus subtilis (strain MN-385), [ 139 ] which are more thermostable than the originally used enzymes. [ 139 ] [ 140 ] Starting in 1982, pullulanases from Aspergillus niger were used in the production of glucose syrup to convert amylopectin to starch (amylose), thereby increasing the yield of glucose. [ 141 ] The reaction is carried out at a pH = 4.6–5.2 and a temperature of 55–60 °C. [ 12 ] Corn syrup has between 20% and 95% glucose in the dry matter. [ 142 ] [ 143 ] The Japanese form of the glucose syrup, Mizuame , is made from sweet potato or rice starch. [ 144 ]
Many crops can be used as the source of starch. Maize , [ 137 ] rice, [ 137 ] wheat , [ 137 ] cassava , [ 137 ] potato , [ 137 ] barley , [ 137 ] sweet potato, [ 145 ] corn husk and sago are all used in various parts of the world. In the United States , corn starch (from maize) is used almost exclusively. Some commercial glucose occurs as a component of invert sugar , a roughly 1:1 mixture of glucose and fructose that is produced from sucrose. In principle, cellulose could be hydrolyzed to glucose, but this process is not yet commercially practical. [ 55 ]
In the US, almost exclusively corn (more precisely, corn syrup) is used as glucose source for the production of isoglucose , which is a mixture of glucose and fructose, since fructose has a higher sweetening power – with same physiological calorific value of 374 kilocalories per 100 g. The annual world production of isoglucose is 8 million tonnes (as of 2011). [ 138 ] When made from corn syrup, the final product is high-fructose corn syrup (HFCS).
Glucose is mainly used for the production of fructose and of glucose-containing foods. In foods, it is used as a sweetener, humectant , to increase the volume and to create a softer mouthfeel . [ 137 ] Various sources of glucose, such as grape juice (for wine) or malt (for beer), are used for fermentation to ethanol during the production of alcoholic beverages . Most soft drinks in the US use HFCS-55 (with a fructose content of 55% in the dry mass), while most other HFCS-sweetened foods in the US use HFCS-42 (with a fructose content of 42% in the dry mass). [ 147 ] In Mexico, on the other hand, soft drinks are sweetened by cane sugar, which has a higher sweetening power. [ 148 ] In addition, glucose syrup is used, inter alia, in the production of confectionery such as candies , toffee and fondant . [ 149 ] Typical chemical reactions of glucose when heated under water-free conditions are caramelization and, in presence of amino acids, the Maillard reaction .
In addition, various organic acids can be biotechnologically produced from glucose, for example by fermentation with Clostridium thermoaceticum to produce acetic acid , with Penicillium notatum for the production of araboascorbic acid , with Rhizopus delemar for the production of fumaric acid , with Aspergillus niger for the production of gluconic acid , with Candida brumptii to produce isocitric acid , with Aspergillus terreus for the production of itaconic acid , with Pseudomonas fluorescens for the production of 2-ketogluconic acid , with Gluconobacter suboxydans for the production of 5-ketogluconic acid , with Aspergillus oryzae for the production of kojic acid , with Lactobacillus delbrueckii for the production of lactic acid , with Lactobacillus brevis for the production of malic acid , with Propionibacter shermanii for the production of propionic acid , with Pseudomonas aeruginosa for the production of pyruvic acid and with Gluconobacter suboxydans for the production of tartaric acid . [ 150 ] [ additional citation(s) needed ] Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of the XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression. [ 151 ] Recently, glucose has been gaining commercial use as a key component of "kits" containing lactic acid and insulin intended to induce hypoglycemia and hyperlactatemia to combat different cancers and infections. [ 152 ]
When a glucose molecule is to be detected at a certain position in a larger molecule, nuclear magnetic resonance spectroscopy , X-ray crystallography analysis or lectin immunostaining is performed with concanavalin A reporter enzyme conjugate, which binds only glucose or mannose.
These reactions have only historical significance:
The Fehling test is a classic method for the detection of aldoses. [ 153 ] Due to mutarotation, glucose is always present to a small extent as an open-chain aldehyde. By adding the Fehling reagents (Fehling (I) solution and Fehling (II) solution), the aldehyde group is oxidized to a carboxylic acid , while the Cu 2+ tartrate complex is reduced to Cu + and forms a brick red precipitate (Cu 2 O).
In the Tollens test , after addition of ammoniacal AgNO 3 to the sample solution, glucose reduces Ag + to elemental silver . [ 154 ]
In Barfoed's test , [ 155 ] a solution of dissolved copper acetate , sodium acetate and acetic acid is added to the solution of the sugar to be tested and subsequently heated in a water bath for a few minutes. Glucose and other monosaccharides rapidly produce a reddish color and reddish brown copper(I) oxide (Cu 2 O).
As a reducing sugar, glucose reacts in the Nylander's test . [ 156 ]
Upon heating a dilute potassium hydroxide solution with glucose to 100 °C, a strong reddish browning and a caramel-like odor develops. [ 157 ] Concentrated sulfuric acid dissolves dry glucose without blackening at room temperature forming sugar sulfuric acid. [ 157 ] [ verification needed ] In a yeast solution, alcoholic fermentation produces carbon dioxide in the ratio of 2.0454 molecules of glucose to one molecule of CO 2 . [ 157 ] Glucose forms a black mass with stannous chloride . [ 157 ] In an ammoniacal silver solution, glucose (as well as lactose and dextrin) leads to the deposition of silver. In an ammoniacal lead acetate solution, white lead glycoside is formed in the presence of glucose, which becomes less soluble on cooking and turns brown. [ 157 ] In an ammoniacal copper solution, yellow copper oxide hydrate is formed with glucose at room temperature, while red copper oxide is formed during boiling (same with dextrin, except for with an ammoniacal copper acetate solution). [ 157 ] With Hager's reagent , glucose forms mercury oxide during boiling. [ 157 ] An alkaline bismuth solution is used to precipitate elemental, black-brown bismuth with glucose. [ 157 ] Glucose boiled in an ammonium molybdate solution turns the solution blue. A solution with indigo carmine and sodium carbonate destains when boiled with glucose. [ 157 ]
In concentrated solutions of glucose with a low proportion of other carbohydrates, its concentration can be determined with a polarimeter. For sugar mixtures, the concentration can be determined with a refractometer , for example in the Oechsle determination in the course of the production of wine.
The enzyme glucose oxidase (GOx) converts glucose into gluconic acid and hydrogen peroxide while consuming oxygen. Another enzyme, peroxidase, catalyzes a chromogenic reaction (Trinder reaction) [ 158 ] of phenol with 4-aminoantipyrine to a purple dye. [ 159 ]
The test-strip method employs the above-mentioned enzymatic conversion of glucose to gluconic acid to form hydrogen peroxide. The reagents are immobilised on a polymer matrix, the so-called test strip, which assumes a more or less intense color. This can be measured reflectometrically at 510 nm with the aid of an LED-based handheld photometer. This allows routine blood sugar determination by nonscientists. In addition to the reaction of phenol with 4-aminoantipyrine, new chromogenic reactions have been developed that allow photometry at higher wavelengths (550 nm, 750 nm). [ 159 ] [ 160 ]
The electroanalysis of glucose is also based on the enzymatic reaction mentioned above. The produced hydrogen peroxide can be amperometrically quantified by anodic oxidation at a potential of 600 mV. [ 161 ] The GOx is immobilized on the electrode surface or in a membrane placed close to the electrode. Precious metals such as platinum or gold are used in electrodes, as well as carbon nanotube electrodes, which e.g. are doped with boron. [ 162 ] Cu–CuO nanowires are also used as enzyme-free amperometric electrodes, reaching a detection limit of 50 μmol/L. [ 163 ] A particularly promising method is the so-called "enzyme wiring", where the electron flowing during the oxidation is transferred via a molecular wire directly from the enzyme to the electrode. [ 164 ]
There are a variety of other chemical sensors for measuring glucose. [ 165 ] [ 166 ] Given the importance of glucose analysis in the life sciences, numerous optical probes have also been developed for saccharides based on the use of boronic acids, [ 167 ] which are particularly useful for intracellular sensory applications where other (optical) methods are not or only conditionally usable. In addition to the organic boronic acid derivatives, which often bind highly specifically to the 1,2-diol groups of sugars, there are also other probe concepts classified by functional mechanisms which use selective glucose-binding proteins (e.g. concanavalin A) as a receptor. Furthermore, methods were developed which indirectly detect the glucose concentration via the concentration of metabolized products, e.g. by the consumption of oxygen using fluorescence-optical sensors. [ 168 ] Finally, there are enzyme-based concepts that use the intrinsic absorbance or fluorescence of (fluorescence-labeled) enzymes as reporters. [ 165 ]
Glucose can be quantified by copper iodometry. [ 169 ]
In particular, for the analysis of complex mixtures containing glucose, e.g. in honey, chromatographic methods such as high performance liquid chromatography and gas chromatography [ 169 ] are often used in combination with mass spectrometry . [ 170 ] [ 171 ] Taking into account the isotope ratios, it is also possible to reliably detect honey adulteration by added sugars with these methods. [ 172 ] Derivatization using silylation reagents is commonly used. [ 173 ] Also, the proportions of di- and trisaccharides can be quantified.
Glucose uptake in cells of organisms is measured with 2-deoxy-D-glucose or fluorodeoxyglucose . [ 115 ] ( 18 F)fluorodeoxyglucose is used as a tracer in positron emission tomography in oncology and neurology, [ 174 ] where it is by far the most commonly used diagnostic agent. [ 175 ]
Glucose
Hexokinase
Glucose 6-phosphate
Glucose-6-phosphate isomerase
Fructose 6-phosphate
Phosphofructokinase-1
Fructose 1,6-bisphosphate
Fructose-bisphosphate aldolase
Dihydroxyacetone phosphate
+
Glyceraldehyde 3-phosphate
Triosephosphate isomerase
2 × Glyceraldehyde 3-phosphate
Glyceraldehyde-3-phosphate dehydrogenase
2 × 1,3-Bisphosphoglycerate
Phosphoglycerate kinase
2 × 3-Phosphoglycerate
Phosphoglycerate mutase
2 × 2-Phosphoglycerate
Phosphopyruvate hydratase ( enolase )
2 × Phosphoenolpyruvate
Pyruvate kinase
2 × Pyruvate | https://en.wikipedia.org/wiki/Glucose |
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation , breakdown , and interconversion of carbohydrates in living organisms .
Carbohydrates are central to many essential metabolic pathways . [ 1 ] Plants synthesize carbohydrates from carbon dioxide and water through photosynthesis , allowing them to store energy absorbed from sunlight internally. [ 2 ] When animals and fungi consume plants, they use cellular respiration to break down these stored carbohydrates to make energy available to cells. [ 2 ] Both animals and plants temporarily store the released energy in the form of high-energy molecules, such as adenosine triphosphate (ATP), for use in various cellular processes. [ 3 ]
While carbohydrates are essential to human biological processes, consuming them is not essential for humans. There are healthy human populations that do not consume carbohydrates. [ 4 ] In humans, carbohydrates are available directly from consumption, from carbohydrate storage, or by conversion from fat components including fatty acids [ 5 ] that are either stored or consumed directly.
Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). [ 2 ] Nearly all organisms that break down glucose utilize glycolysis. [ 2 ] Glucose regulation and product use are the primary categories in which these pathways differ between organisms. [ 2 ] In some tissues and organisms, glycolysis is the sole method of energy production. [ 2 ] This pathway is common to both anaerobic and aerobic respiration. [ 1 ]
Glycolysis consists of ten steps, split into two phases. [ 2 ] During the first phase, it requires the breakdown of two ATP molecules. [ 1 ] During the second phase, chemical energy from the intermediates is transferred into ATP and NADH. [ 2 ] The breakdown of one molecule of glucose results in two molecules of pyruvate, which can be further oxidized to access more energy in later processes. [ 1 ]
Glycolysis can be regulated at different steps of the process through feedback regulation. The step that is regulated the most is the third step. This regulation is to ensure that the body is not over-producing pyruvate molecules. The regulation also allows for the storage of glucose molecules into fatty acids. [ 6 ] There are various enzymes that are used throughout glycolysis. The enzymes upregulate , downregulate , and feedback regulate the process.
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. [ 7 ] In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys . It is one of two primary mechanisms – the other being degradation of glycogen ( glycogenolysis ) – used by humans and many other animals to maintain blood sugar levels , avoiding low levels ( hypoglycemia ). [ 8 ] In ruminants , because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. [ 9 ] In many other animals, the process occurs during periods of fasting , starvation , low-carbohydrate diets , or intense exercise .
In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins , these substrates include glucogenic amino acids (although not ketogenic amino acids ); from breakdown of lipids (such as triglycerides ), they include glycerol , odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism they include lactate from the Cori cycle . Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose. [ 5 ] Although most gluconeogenesis occurs in the liver, the relative contribution of gluconeogenesis by the kidney is increased in diabetes and prolonged fasting. [ 10 ]
The gluconeogenesis pathway is highly endergonic until it is coupled to the hydrolysis of ATP or guanosine triphosphate (GTP), effectively making the process exergonic . For example, the pathway leading from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are supplied from fatty acid catabolism via beta oxidation . [ 11 ]
Glycogenolysis refers to the breakdown of glycogen. [ 12 ] In the liver, muscles, and the kidney, this process occurs to provide glucose when necessary. [ 12 ] A single glucose molecule is cleaved from a branch of glycogen, and is transformed into glucose-1-phosphate during this process. [ 1 ] This molecule can then be converted to glucose-6-phosphate , an intermediate in the glycolysis pathway. [ 1 ]
Glucose-6-phosphate can then progress through glycolysis. [ 1 ] Glycolysis only requires the input of one molecule of ATP when the glucose originates in glycogen. [ 1 ] Alternatively, glucose-6-phosphate can be converted back into glucose in the liver and the kidneys, allowing it to raise blood glucose levels if necessary. [ 2 ]
Glucagon in the liver stimulates glycogenolysis when the blood glucose is lowered, known as hypoglycemia. [ 12 ] The glycogen in the liver can function as a backup source of glucose between meals. [ 2 ] Liver glycogen mainly serves the central nervous system. Adrenaline stimulates the breakdown of glycogen in the skeletal muscle during exercise. [ 12 ] In the muscles, glycogen ensures a rapidly accessible energy source for movement. [ 2 ]
Glycogenesis refers to the process of synthesizing glycogen. [ 12 ] In humans, glucose can be converted to glycogen via this process. [ 2 ] Glycogen is a highly branched structure, consisting of the core protein Glycogenin , surrounded by branches of glucose units, linked together. [ 2 ] [ 12 ] The branching of glycogen increases its solubility, and allows for a higher number of glucose molecules to be accessible for breakdown at the same time. [ 2 ] Glycogenesis occurs primarily in the liver, skeletal muscles, and kidney. [ 2 ] The Glycogenesis pathway consumes energy, like most synthetic pathways, because an ATP and a UTP are consumed for each molecule of glucose introduced. [ 13 ]
The pentose phosphate pathway is an alternative method of oxidizing glucose. [ 12 ] It occurs in the liver, adipose tissue , adrenal cortex , testis , mammary glands , phagocytes , and red blood cells . [ 12 ] It produces products that are used in other cell processes, while reducing NADP to NADPH. [ 12 ] [ 14 ] This pathway is regulated through changes in the activity of glucose-6-phosphate dehydrogenase. [ 14 ]
Fructose must undergo certain extra steps in order to enter the glycolysis pathway. [ 2 ] Enzymes located in certain tissues can add a phosphate group to fructose. [ 12 ] This phosphorylation creates fructose-6-phosphate, an intermediate in the glycolysis pathway that can be broken down directly in those tissues. [ 12 ] This pathway occurs in the muscles, adipose tissue, and kidney. [ 12 ] In the liver, enzymes produce fructose-1-phosphate, which enters the glycolysis pathway and is later cleaved into glyceraldehyde and dihydroxyacetone phosphate. [ 2 ]
Lactose, or milk sugar, consists of one molecule of glucose and one molecule of galactose. [ 12 ] After separation from glucose, galactose travels to the liver for conversion to glucose. [ 12 ] Galactokinase uses one molecule of ATP to phosphorylate galactose. [ 2 ] The phosphorylated galactose is then converted to glucose-1-phosphate, and then eventually glucose-6-phosphate, which can be broken down in glycolysis. [ 2 ]
Many steps of carbohydrate metabolism allow the cells to access energy and store it more transiently in ATP. [ 15 ] The cofactors NAD + and FAD are sometimes reduced during this process to form NADH and FADH 2 , which drive the creation of ATP in other processes. [ 15 ] A molecule of NADH can produce 1.5–2.5 molecules of ATP, whereas a molecule of FADH 2 yields 1.5 molecules of ATP. [ 16 ]
Typically, the complete breakdown of one molecule of glucose by aerobic respiration (i.e. involving glycolysis, the citric-acid cycle and oxidative phosphorylation , the last providing the most energy) is usually about 30–32 molecules of ATP. [ 16 ] Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy . [ 3 ]
Humans can consume a variety of carbohydrates, digestion breaks down complex carbohydrates into simple monomers ( monosaccharides ): glucose , fructose , mannose and galactose . After resorption in the gut , the monosaccharides are transported, through the portal vein , to the liver, where all non-glucose monosacharids (fructose, galactose) are transformed into glucose as well. [ 17 ] Glucose ( blood sugar ) is distributed to cells in the tissues, where it is broken down via cellular respiration , or stored as glycogen . [ 3 ] [ 17 ] In cellular (aerobic) respiration, glucose and oxygen are metabolized to release energy, with carbon dioxide and water as endproducts. [ 2 ] [ 17 ]
Glucoregulation is the maintenance of steady levels of glucose in the body.
Hormones released from the pancreas regulate the overall metabolism of glucose. [ 18 ] Insulin and glucagon are the primary hormones involved in maintaining a steady level of glucose in the blood, and the release of each is controlled by the amount of nutrients currently available. [ 18 ] The amount of insulin released in the blood and sensitivity of the cells to the insulin both determine the amount of glucose that cells break down. [ 17 ] Increased levels of glucagon activates the enzymes that catalyze glycogenolysis, and inhibits the enzymes that catalyze glycogenesis. [ 15 ] Conversely, glycogenesis is enhanced and glycogenolysis inhibited when there are high levels of insulin in the blood. [ 15 ]
The level of circulatory glucose (known informally as "blood sugar"), as well as the detection of nutrients in the Duodenum is the most important factor determining the amount of glucagon or insulin produced. The release of glucagon is precipitated by low levels of blood glucose, whereas high levels of blood glucose stimulates cells to produce insulin. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin. [ 19 ] In humans, insulin is made by beta cells in the pancreas , fat is stored in adipose tissue cells, and glycogen is both stored and released as needed by liver cells. Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells.
Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support (e.g. chitin , cellulose ) or for energy storage (e.g. glycogen , starch ). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA , which is a feed stock for the fatty acid synthesis pathway; fatty acids , triglycerides , and other lipids are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. Gluconeogenesis permits glucose to be synthesized from various sources, including lipids. [ 20 ]
In some animals (such as termites ) [ 21 ] and some microorganisms (such as protists and bacteria ), cellulose can be disassembled during digestion and absorbed as glucose. [ 22 ] | https://en.wikipedia.org/wiki/Glucose_metabolism |
Glucose phosphate broth is used to perform methyl red (MR) test and Voges–Proskauer test (VP).
pH – 6.9
It is used to determine the ability of an organism to produce mixed acids by fermentation of glucose and to overcome the buffering capacity of the medium.
Inoculate MacConkey's (Glucose phosphate broth) with pure culture of test organism. Incubate the broth at 35 °C for 48–72 hours.
After incubation add 5 drops of methyl red directly into the broth, through the sides of the tube.
The development of stable red color in the surface of the medium indicates sufficient acid production to lower the pH to 4.4 and constitute a positive test. Since other organism may produce lesser quantities of acid from the test substrate , an intermediate orange color between yellow and red may develop. This does not indicate positive test.
Positive and negative controls should be run after preparation of each lot of medium.
Positive control: Escherichia coli
Negative control: Klebsiella
It is used to determine the ability of some organisms to produce a neutral end product, acetyl methyl carbinol ( acetoin ) from glucose fermentation. The production of acetoin, a neutral reacting end product produced by members such as Klebsiella , Enterobacter etc., is the chief end product of glucose metabolism and form less quantities of mixed acids. In the presence of atmospheric oxygen and 40% KOH, acetoin is converted to diacetyl and α-naphthol serves as catalyst to bring out red color complex.
Glucose Phosphate Broth
A: α-naphthol – 5 g
Inoculate a tube of glucose phosphate broth with a pure inoculum of test organism and incubate at 35 °C for 24 hours.
To 1 mL of this broth add 0.6 mL of 5% α-Naphthol followed by 0.2 mL of 40% KOH. Shake the tube gently to expose the medium to atmospheric oxygen and allow the tube to remain undisturbed for 10–15 minutes.
A positive test is represented by the development of red color in 15 minutes or more after addition of the reagents , indicating the presence of diacetyl, the oxidation product of acetoin. The test should be red, after standing for 1 hour because negative VP cultures may produce copper-like colour potentially resulting in a false positive interpretation, also because due to action of the reagents when mixed.
Positive and negative controls should be run after preparation of each lot of medium.
Positive control: Klebsiella
Negative control: Escherichia coli [ 1 ] | https://en.wikipedia.org/wiki/Glucose_phosphate_broth |
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane , a process known as facilitated diffusion . Because glucose is a vital source of energy for all life, these transporters are present in all phyla . The GLUT or SLC2A family are a protein family that is found in most mammalian cells . 14 GLUTS are encoded by the human genome . GLUT is a type of uniporter transporter protein.
Most non- autotrophic cells are unable to produce free glucose because they lack expression of glucose-6-phosphatase and, thus, are involved only in glucose uptake and catabolism . Usually produced only in hepatocytes , in fasting conditions, other tissues such as the intestines, muscles, brain, and kidneys are able to produce glucose following activation of gluconeogenesis .
In Saccharomyces cerevisiae glucose transport takes place through facilitated diffusion . [ 1 ] The transport proteins are mainly from the Hxt family, but many other transporters have been identified. [ 2 ]
GLUTs are integral membrane proteins that contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane . GLUT proteins transport glucose and related hexoses according to a model of alternate conformation, [ 5 ] [ 6 ] [ 7 ] which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes a conformational change associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are, it seems, located in transmembrane segments 9, 10, 11; [ 8 ] also, the DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate. [ 9 ] [ 10 ]
Each glucose transporter isoform plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions. [ 11 ] To date, 14 members of the GLUT/SLC2 have been identified. [ 12 ] On the basis of sequence similarities, the GLUT family has been divided into three subclasses.
Class I comprises the well-characterized glucose transporters GLUT1-GLUT4. [ 13 ]
Class II comprises:
Class III comprises:
Most members of classes II and III have been identified recently in homology searches of EST databases and the sequence information provided by the various genome projects .
The function of these new [ when? ] glucose transporter isoforms is still not clearly defined at present. Several of them (GLUT6, GLUT8) are made of motifs that help retain them intracellularly and therefore prevent glucose transport. Whether mechanisms exist to promote cell-surface translocation of these transporters is not yet known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.
In August 1960, in Prague , Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption. [ 15 ] Crane 's discovery of cotransport was the first ever proposal of flux coupling in biology. [ 16 ] Crane in 1961 was the first to formulate the cotransport concept to explain active transport. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type. [ 17 ] | https://en.wikipedia.org/wiki/Glucose_transporter |
Glucosidases are the glycoside hydrolase enzymes categorized under the EC number 3.2.1. [ 1 ]
Alpha-glucosidases are enzymes involved in breaking down complex carbohydrates such as starch and glycogen into their monomers . [ 2 ]
They catalyze the cleavage of individual glucosyl residues from various glycoconjugates including alpha- or beta-linked polymers of glucose. This enzyme convert complex sugars into simpler ones.
Different sources include different members in this class. Members marked with a "#" are considered by MeSH to be glucosidases.
Alpha-glucosidases are targeted by alpha-glucosidase inhibitors such as acarbose and miglitol to control diabetes mellitus type 2 . | https://en.wikipedia.org/wiki/Glucosidases |
Glucosinolates are natural components of many pungent plants such as mustard , cabbage , and horseradish . The pungency of those plants is due to mustard oils produced from glucosinolates when the plant material is chewed, cut, or otherwise damaged. These natural chemicals most likely contribute to plant defence against pests and diseases , and impart a characteristic bitter flavor property to cruciferous vegetables . [ 1 ]
Glucosinolates occur as secondary metabolites of almost all plants of the order Brassicales . This includes the economically important family Brassicaceae as well as Capparaceae and Caricaceae .
Outside of the Brassicales, the genera Drypetes [ 2 ] and Putranjiva in the family Putranjivaceae , are the only other known occurrence of glucosinolates.
Glucosinolates occur in various edible plants such as cabbage (white cabbage, Chinese cabbage , broccoli ), Brussels sprouts , watercress , arugula , horseradish , capers , and radishes where the breakdown products often contribute a significant part of the distinctive taste. The glucosinolates are also found in seeds of these plants. [ 1 ] [ 3 ]
Glucosinolates constitute a natural class of organic compounds that contain sulfur and nitrogen and are derived from glucose and an amino acid .
They are water- soluble anions and belong to the glucosides . Every glucosinolate contains a central carbon atom, which is bound to the sulfur atom of the thioglucose group, and via a nitrogen atom to a sulfate group (making a sulfated aldoxime ). In addition, the central carbon is bound to a side group; different glucosinolates have different side groups, and it is variation in the side group that is responsible for the variation in the biological activities of these plant compounds.
The essence of glucosinolate chemistry is their ability to convert into an isothiocyanate (a "mustard oil") upon hydrolysis of the thioglucoside bond by the enzyme myrosinase. [ 4 ]
The semisystematic naming of glucosinolates consists of the chemical name of the group "R" in the diagram followed by "glucosinolate", with or without a space. For example, allylglucosinolate and allyl glucosinolate refer to the same compound: both versions are found in the literature. [ 5 ] Isothiocyanates are conventionally written as two words. [ 4 ]
The following are some glucosinolates and their isothiocyanate products: [ 4 ]
Sinigrin was first of the class to be isolated — in 1839 as its potassium salt. [ 6 ] Its chemical structure had been established by 1930, showing that it is a glucose derivative with β- D -glucopyranose configuration. It was unclear at that time whether the C=N bond was in the Z (or syn ) form , with sulfur and oxygen substituents on the same side of the double bond, or the alternative E form in which they are on opposite sides. The matter was settled by X-ray crystallography in 1963. [ 7 ] [ 8 ] It is now known that all natural glucosinolates are of Z form, although both forms can be made in the laboratory. [ 5 ] The "ate" ending in the naming of these compounds implies that they are anions at physiological pH and an early name for this allylglucosinolate was potassium myronate. [ 6 ] Care must be taken when discussing these compounds since some older publications do not make it clear whether they refer to the anion alone, its corresponding acid or the potassium salt . [ 5 ]
About 132 different glucosinolates are known to occur naturally in plants. They are biosynthesized from amino acids : so-called aliphatic glucosinolates derived from mainly methionine , but also alanine , leucine , isoleucine , or valine . (Most glucosinolates are actually derived from chain-elongated homologues of these amino acids, e.g. glucoraphanin is derived from dihomomethionine, which is methionine chain-elongated twice.) Aromatic glucosinolates include indolic glucosinolates, such as glucobrassicin , derived from tryptophan and others from phenylalanine , its chain-elongated homologue homophenylalanine, and sinalbin derived from tyrosine . [ 4 ]
Full details of the sequence of reactions that converts individual amino acids into the corresponding glucosinolate have been studied in the cress Arabidopsis thaliana . [ 9 ] [ 5 ]
A sequence of seven enzyme-catalysed steps is used. The sulfur atom is incorporated from glutathione (GSH) and the sugar component is added to the resulting thiol derivative by a glycosyltransferase before the final sulfonation step. [ 10 ]
The plants contain the enzyme myrosinase , which, in the presence of water, cleaves off the glucose group from a glucosinolate. [ 11 ] The remaining molecule then quickly converts to an isothiocyanate , a nitrile , or a thiocyanate ; these are the active substances that serve as defense for the plant. Glucosinolates are also called mustard oil glycosides . The standard product of the reaction is the isothiocyanate (mustard oil); the other two products mainly occur in the presence of specialised plant proteins that alter the outcome of the reaction. [ 12 ]
In the chemical reaction illustrated above, the red curved arrows in the left side of figure are simplified compared to reality, as the role of the enzyme myrosinase is not shown. However, the mechanism shown is fundamentally in accordance with the enzyme-catalyzed reaction.
In contrast, the reaction illustrated by red curved arrows at the right side of the figure, depicting the rearrangement of atoms resulting in the isothiocyanate, is expected to be non-enzymatic. This type of rearrangement can be named a Lossen rearrangement , or a Lossen- like rearrangement, since this name was first used for the analogous reaction leading to an organic isocyanate (R-N=C=O).
To prevent damage to the plant itself, the myrosinase and glucosinolates are stored in separate compartments of the cell or in different cells in the tissue, and come together only or mainly under conditions of physical injury (see Myrosinase ).
The use of glucosinolate-containing crops as primary food source for animals can have negative effects if the concentration of glucosinolate is higher than what is acceptable for the animal in question, because some glucosinolates have been shown to have toxic effects (mainly as goitrogens and anti-thyroid agents ) in livestock at high doses. [ 13 ] However, tolerance level to glucosinolates varies even within the same genus (e.g. Acomys cahirinus and Acomys russatus ). [ 14 ]
Dietary amounts of glucosinolate are not toxic to humans given normal iodine intake. [ 15 ]
The glucosinolate sinigrin , among others, was shown to be responsible for the bitterness of cooked cauliflower and Brussels sprouts . [ 1 ] [ 16 ] Glucosinolates may alter animal eating behavior. [ 17 ]
The isothiocyanates formed from glucosinolates are under laboratory research to assess the expression and activation of enzymes that metabolize xenobiotics , such as carcinogens . [ 18 ] Observational studies have been conducted to determine if consumption of cruciferous vegetables affects cancer risk in humans, but there is insufficient clinical evidence to indicate that consuming isothiocyanates in cruciferous vegetables is beneficial, according to a 2017 review. [ 18 ]
Glucosinolates and their products have a negative effect on many insects, resulting from a combination of deterrence and toxicity. In an attempt to apply this principle in an agronomic context, some glucosinolate-derived products can serve as antifeedants , i.e., natural pesticides . [ 19 ]
In contrast, the diamondback moth , a pest of cruciferous plants, may recognize the presence of glucosinolates, allowing it to identify the proper host plant. [ 20 ] Indeed, a characteristic, specialised insect fauna is found on glucosinolate-containing plants, including butterflies, such as large white , small white , and orange tip , but also certain aphids , moths, such as the southern armyworm , sawflies , and flea beetles . [ citation needed ] For instance, the large white butterfly deposits its eggs on these glucosinolate-containing plants, and the larvae survive even with high levels of glucosinolates and eat plant material containing glucosinolates. [ 21 ] The whites and orange tips all possess the so-called nitrile specifier protein , which diverts glucosinolate hydrolysis toward nitriles rather than reactive isothiocyanates . [ 22 ] In contrast, the diamondback moth possesses a completely different protein, glucosinolate sulfatase , which desulfates glucosinolates, thereby making them unfit for degradation to toxic products by myrosinase . [ 23 ]
Other kinds of insects (specialised sawflies and aphids) sequester glucosinolates. [ 24 ] In specialised aphids, but not in sawflies, a distinct animal myrosinase is found in muscle tissue, leading to degradation of sequestered glucosinolates upon aphid tissue destruction. [ 25 ] This diverse panel of biochemical solutions to the same plant chemical plays a key role in the evolution of plant-insect relationships. [ 26 ]
Plants produce glucosinolates in response to the degree of herbivory being suffered. Their production in relation to atmospheric CO 2 concentrations is complex: increased CO 2 can give increased, decreased or unchanged production and there may be genetic variation within the Brassicales. [ 27 ] [ 28 ] | https://en.wikipedia.org/wiki/Glucosinolate |
Glucuronidation is often involved in drug metabolism of substances such as drugs , pollutants, bilirubin , androgens , estrogens , mineralocorticoids , glucocorticoids , fatty acid derivatives, retinoids , and bile acids . These linkages involve glycosidic bonds . [ 1 ]
Glucuronidation consists of transfer of the glucuronic acid component of uridine diphosphate glucuronic acid to a substrate by any of several types of UDP-glucuronosyltransferase .
UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate ) is an intermediate in the process and is formed in the liver . One example is the N-glucuronidation of an aromatic amine , 4-aminobiphenyl , by UGT1A4 or UGT1A9 from human, rat, or mouse liver. [ 2 ]
The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water - soluble than the non-glucuronic acid-containing substances from which they were originally synthesised. The human body uses glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or feces (via bile from the liver). Hormones are glucuronidated to allow for easier transport around the body. Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a broad range of potential therapeutics. Sometimes toxic substances are also less toxic after glucuronidation.
The conjugation of xenobiotic molecules with hydrophilic molecular species such as glucuronic acid is known as phase II metabolism .
Glucuronidation occurs mainly in the liver , although the enzyme responsible for its catalysis , UDP-glucuronyltransferase , has been found in all major body organs (e.g., intestine , kidneys , brain , adrenal gland , spleen , and thymus ). [ 3 ] [ 4 ]
Various factors affect the rate of glucuronidation, which in turn will affect these molecules' clearance from the body. Generally, an increased rate of glucuronidation results in a loss of potency for the target drugs or compounds.
Many drugs which are substrates for glucuronidation as part of their metabolism are significantly affected by inhibitors or inducers of their specific glucuronisyltransferase types: | https://en.wikipedia.org/wiki/Glucuronidation |
A glucuronide , also known as glucuronoside , is any substance produced by linking glucuronic acid to another substance via a glycosidic bond . [ 1 ] The glucuronides belong to the glycosides .
Glucuronidation , the conversion of chemical compounds to glucuronides, is a method that animals use to assist in the excretion of toxic substances, drugs or other substances that cannot be used as an energy source. Glucuronic acid is attached via a glycosidic bond to the substance, and the resulting glucuronide, which has a much higher water solubility than the original substance, is eventually excreted by the kidneys . [ 2 ]
Enzymes that cleave the glycosidic bond of a glucuronide are called glucuronidases .
Carboxylic acids are a common functional group in many medications, such as NSAIDS , anticonvulsants , and diuretics . One common pathway for the clearance of carboxylic-acid-containing drugs is via glucuronidation. By conjugating one such drug to a glucuronide, the resulting compound should be less toxic and exhibit rapid clearance from the body. Many in vitro studies have provided compelling evidence to suggest, however, that acyl glucuronidation could have adverse pharmalogical effects due to protein adduction. Two mechanisms in which acyl glucuronides lead to protein adduction are: transacylation of the 1-O-β-glucuronide and glycation of the 3-O-β-glucuronide. [ 3 ]
Glucuronidation of nitrogen-containing compounds generally form quaternary ammonium-linked glucuronides. Nicotine , which contains a pyridine ring and a pyrrolidine ring, [ 4 ] is conjugated at the pyridine nitrogen during drug metabolism. There are two enantiomers of nicotine: S(-)-nicotine and R(+)-nicotine. S(-)-nicotine is the more common stereoisomer of the compound, primarily forming through combustion of nicotine-containing drugs. The S(-)-nicotine N1 -glucuronide has a lower K m and higher V max for liver microsomes than the N(+)-nicotine N1 -glucuronide, suggesting that the body has evolved to favor the eradication of the more common N-linked moiety [ 5 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it .
This toxicology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glucuronide |
Glucuronoxylans are the primary components of hemicellulose as found in hardwood trees, for example birch. [ 1 ] They are hemicellulosic plant cell wall polysaccharides , containing glucuronic acid and xylose as its main constituents. They are linear polymers of β-D-xylopyranosyl units linked by (1→4) glycosidic bonds, with many of the xylose units substituted with 2, 3 or 2,3-linked glucuronate residue, which are often methylated at position 4. Most of the glucuronoxylans have single 4-O-methyl-α-D-glucopyranosyl uronate residues (MeGlcA) attached at position 2. This structural type is usually named as 4-O-methyl-D-glucurono-D-xylan (MGX).
Angiosperm (hardwood) glucuronoxylans also have a high rate of substitution (70-80%) by acetyl groups, at position 2 and/or 3 of the β-D-xylopyranosyl, conferring on the xylan its partial solubility in water.
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glucuronoxylan |
In particle physics , a glueball (also gluonium , gluon-ball ) is a hypothetical composite particle . [ 1 ] It consists solely of gluon particles, without valence quarks . Such a state is possible because gluons carry color charge and experience the strong interaction between themselves. Glueballs are extremely difficult to identify in particle accelerators , because they mix with ordinary meson states. [ 2 ] [ 3 ] In pure gauge theory , glueballs are the only states of the spectrum and some of them are stable. [ 4 ]
Theoretical calculations show that glueballs should exist at energy ranges accessible with current collider technology. However, due to the aforementioned difficulty (among others), they have so far not been observed and identified with certainty, [ 5 ] although phenomenological calculations have suggested that an experimentally identified glueball candidate, denoted f 0 (1710), has properties consistent with those expected of a Standard Model glueball. [ 6 ]
The prediction that glueballs exist is one of the most important predictions of the Standard Model of particle physics that has not yet been confirmed experimentally. [ 7 ] [ failed verification ] Glueballs are the only particles predicted by the Standard Model with total angular momentum ( J ) (sometimes called "intrinsic spin ") that could be either 2 or 3 in their ground states .
Experimental evidence was announced in 2021, by the TOTEM collaboration at the LHC in collaboration with the DØ collaboration at the former Tevatron collider at Fermilab , of odderon (a composite gluonic particle with odd C-parity ) exchange. This exchange, associated with a quarkless three-gluon vector glueball, was identified in the comparison of proton–proton and proton–antiproton scattering. [ 8 ] [ 9 ] [ 10 ] In 2024, the X(2370) particle was determined to have mass and spin parity consistent with that of a glueball. [ 11 ] However, other exotic particle candidates such as a tetraquark could not be ruled out. [ 12 ]
In principle, it is theoretically possible for all properties of glueballs to be calculated exactly and derived directly from the equations and fundamental physical constants of quantum chromodynamics (QCD) without further experimental input. So, the predicted properties of these hypothetical particles can be described in exquisite detail using only Standard Model physics that have wide acceptance in the theoretical physics literature. But, there is considerable uncertainty in the measurement of some of the relevant key physical constants, and the QCD calculations are so difficult that solutions to these equations are almost always numerical approximations (calculated using several very different methods). This can lead to variation in theoretical predictions of glueball properties, like mass and branching ratios in glueball decays.
Theoretical studies of glueballs have focused on glueballs consisting of either two gluons or three gluons, by analogy to mesons and baryons that have two and three quarks respectively. As in the case of mesons and baryons, glueballs would be QCD color charge neutral. The baryon number of a glueball is zero.
Double-gluon glueballs can have total angular momentum J = 0 (which are either scalar or pseudo-scalar ) or J = 2 ( tensor ). Triple-gluon glueballs can have total angular momentum J = 1 ( vector boson ) or 3 ( third-order tensor boson ). All glueballs have integer total angular momentum that implies that they are bosons rather than fermions .
Glueballs are the only particles predicted by the Standard Model with total angular momentum ( J ) (sometimes called "intrinsic spin" ) that could be either 2 or 3 in their ground states, although mesons made of two quarks with J = 0 and J = 1 with similar masses have been observed and excited states of other mesons can have these values of total angular momentum.
All glueballs would have an electric charge of zero, as gluons themselves do not have an electric charge.
Glueballs are predicted by quantum chromodynamics to be massive, despite the fact that gluons themselves have zero rest mass in the Standard Model. Glueballs with all four possible combinations of quantum numbers P ( spatial parity ) and C ( charge parity ) for every possible total angular momentum have been considered, producing at least fifteen possible glueball states including excited glueball states that share the same quantum numbers but have differing masses with the lightest states having masses as low as 1.4 GeV/ c 2 (for a glueball with quantum numbers J = 0, P = +1, C = +1, or equivalently J PC = 0 ++ ), and the heaviest states having masses as great as almost 5 GeV/ c 2 (for a glueball with quantum numbers J = 0, P = +1, C = −1, or J PC = 0 +− ). [ 5 ]
These masses are on the same order of magnitude as the masses of many experimentally observed mesons and baryons , as well as to the masses of the tau lepton , charm quark , bottom quark , some hydrogen isotopes, and some helium isotopes.
Just as all Standard Model mesons and baryons, except the proton, are unstable in isolation, all glueballs are predicted by the Standard Model to be unstable in isolation, with various QCD calculations predicting the total decay width (which is functionally related to half-life) for various glueball states. QCD calculations also make predictions regarding the expected decay patterns of glueballs. [ 13 ] [ 14 ] For example, glueballs would not have radiative or two photon decays, but would have decays into pairs of pions , pairs of kaons , or pairs of eta mesons . [ 13 ]
Standard Model glueballs are extremely ephemeral (decaying almost immediately into more stable decay products) and are only generated in high energy physics. Thus in the natural conditions found on Earth that humans can easily observe, glueballs arise only synthetically. They are scientifically notable mostly because they are a testable prediction of the Standard Model, and not because of phenomenological impact on macroscopic processes, or their engineering applications.
Lattice QCD provides a way to study the glueball spectrum theoretically and from first principles. Some of the first quantities calculated using lattice QCD methods (in 1980) were glueball mass estimates. [ 16 ] Morningstar and Peardon [ 17 ] computed in 1999 the masses of the lightest glueballs in QCD without dynamical quarks. The three lowest states are tabulated below. The presence of dynamical quarks would slightly alter these data, but also makes the computations more difficult. Since that time calculations within QCD (lattice and sum rules) find the lightest glueball to be a scalar with mass in the range of about 1000–1700 MeV/ c 2 . [ 5 ] Lattice predictions for scalar and pseudoscalar glueballs, including their excitations, were confirmed by Dyson–Schwinger/Bethe–Salpeter equations in Yang–Mills theory . [ 18 ]
Particle accelerator experiments are often able to identify unstable composite particles and assign masses to those particles to a precision of approximately 10 MeV/ c 2 , without being able to immediately assign to the particle resonance that is observed all of the properties of that particle. Scores of such particles have been detected, although particles detected in some experiments but not others can be viewed as doubtful.
Many of these candidates have been the subject of active investigation for at least eighteen years. [ 13 ] The GlueX experiment has been specifically designed to produce more definitive experimental evidence of glueballs. [ 19 ]
Some of the candidate particle resonances that could be glueballs, although the evidence is not definitive, include the following: | https://en.wikipedia.org/wiki/Glueball |
Glugging (also referred to as "the glug-glug process" [ 1 ] ) is the physical phenomenon which occurs when a liquid is poured rapidly from a vessel with a narrow opening, such as a bottle. [ 2 ] [ 3 ] It is a facet of fluid dynamics .
As liquid is poured from a bottle, the air pressure in the bottle is lowered, and air at higher pressure from outside the bottle is forced into the bottle, in the form of a bubble , impeding the flow of liquid. [ 3 ] Once the bubble enters, more liquid escapes, and the process is repeated. [ 3 ] The reciprocal action of glugging creates a rhythmic sound. [ 4 ] The English word " glug " is onomatopoeic , describing this sound. [ 5 ] Onomatopoeias in other languages include Gluckern (German).
Academic papers have been written about the physics of glugging, [ 1 ] [ 2 ] [ 4 ] [ 6 ] and about the impact of glugging sounds on consumers' perception of products such as wine . [ 7 ] [ 8 ] Research into glugging has been done using high-speed photography . [ 4 ]
Factors which affect glugging are the viscosity of the liquid, its carbonation , the size and shape of the container's neck and its opening (collectively referred to as "bottle geometry"), the angle at which the container is held, and the ratio of air to liquid in the bottle (which means that the rate and the sound of the glugging changes as the bottle empties). [ 3 ] [ 4 ] [ 7 ] | https://en.wikipedia.org/wiki/Glugging |
The Gluhareff Pressure Jet (or tip jet ) is a type of jet engine that, like a valveless pulse jet , has no moving parts . It was invented by Eugene Michael Gluhareff , a Russian-American [ 1 ] engineer who envisioned it as a power plant for personal helicopters and compact aircraft such as microlights .
Having no moving parts, the engine works by having a coiled pipe in the combustion chamber that superheats the fuel ( propane ) before being injected into the air-fuel inlet. In the combustion chamber, the fuel/air mixture ignites and burns, creating thrust as it leaves through the exhaust pipe. Induction and compression of the fuel/air mixture is done both by the pressure of propane as it is injected, along with the sound waves created by combustion acting on the intake stacks. [ 2 ]
The engine has three intake stages, which are sized according to the sound created by the combustion process when running. This has exactly the same effect as the turbine and compressor in a turbojet , creating a vacuum that sucks in air. The intakes, along with the exhaust, are sonically tuned so that the locations of the pressure antinodes of the Mach disks in the propane stream match the locations of the intake apertures. Thus atmospheric pressure augments air intake as much as possible. Early prototypes produced very small amounts of thrust, before Gluharev developed it from early experiments on producing thrust from using the pressurized fuel's kinetic energy to suck in the air and compress it prior to combustion. [ 3 ]
A 1949 reference to a very similar concept exists. [ 4 ] Although described as a ram jet, this version heats the fuel within a closed space to create the pressure for injection and compression of the entrained air in a similar manner to the Gluhareff design and is in all fundamental respects a pressure jet of the same type. | https://en.wikipedia.org/wiki/Gluhareff_Pressure_Jet |
In mathematics , the gluing axiom is introduced to define what a sheaf F {\displaystyle {\mathcal {F}}} on a topological space X {\displaystyle X} must satisfy, given that it is a presheaf , which is by definition a contravariant functor
to a category C {\displaystyle C} which initially one takes to be the category of sets . Here O ( X ) {\displaystyle {\mathcal {O}}(X)} is the partial order of open sets of X {\displaystyle X} ordered by inclusion maps ; and considered as a category in the standard way, with a unique morphism
if U {\displaystyle U} is a subset of V {\displaystyle V} , and none otherwise.
As phrased in the sheaf article, there is a certain axiom that F {\displaystyle F} must satisfy, for any open cover of an open set of X {\displaystyle X} . For example, given open sets U {\displaystyle U} and V {\displaystyle V} with union X {\displaystyle X} and intersection W {\displaystyle W} , the required condition is that
In less formal language, a section s {\displaystyle s} of F {\displaystyle F} over X {\displaystyle X} is equally well given by a pair of sections : ( s ′ , s ″ ) {\displaystyle (s',s'')} on U {\displaystyle U} and V {\displaystyle V} respectively, which 'agree' in the sense that s ′ {\displaystyle s'} and s ″ {\displaystyle s''} have a common image in F ( W ) {\displaystyle {\mathcal {F}}(W)} under the respective restriction maps
and
The first major hurdle in sheaf theory is to see that this gluing or patching axiom is a correct abstraction from the usual idea in geometric situations. For example, a vector field is a section of a tangent bundle on a smooth manifold ; this says that a vector field on the union of two open sets is (no more and no less than) vector fields on the two sets that agree where they overlap.
Given this basic understanding, there are further issues in the theory, and some will be addressed here. A different direction is that of the Grothendieck topology , and yet another is the logical status of 'local existence' (see Kripke–Joyal semantics ).
To rephrase this definition in a way that will work in any category C {\displaystyle C} that has sufficient structure, we note that we can write the objects and morphisms involved in the definition above in a diagram which we will call (G), for "gluing":
Here the first map is the product of the restriction maps
and each pair of arrows represents the two restrictions
and
It is worthwhile to note that these maps exhaust all of the possible restriction maps among U {\displaystyle U} , the U i {\displaystyle U_{i}} , and the U i ∩ U j {\displaystyle U_{i}\cap U_{j}} .
The condition for F {\displaystyle {\mathcal {F}}} to be a sheaf is that for any open set U {\displaystyle U} and any collection of open sets { U i } i ∈ I {\displaystyle \{U_{i}\}_{i\in I}} whose union is U {\displaystyle U} , the diagram (G) above is an equalizer .
One way of understanding the gluing axiom is to notice that U {\displaystyle U} is the colimit of the following diagram:
The gluing axiom says that F {\displaystyle {\mathcal {F}}} turns colimits of such diagrams into limits.
In some categories, it is possible to construct a sheaf by specifying only some of its sections. Specifically, let X {\displaystyle X} be a topological space with basis { B i } i ∈ I {\displaystyle \{B_{i}\}_{i\in I}} . We can define a category O ′ ( X ) {\displaystyle {\mathcal {O}}'(X)} to be the full subcategory of O ( X ) {\displaystyle {\mathcal {O}}(X)} whose objects are the { B i } {\displaystyle \{B_{i}\}} . A B-sheaf on X {\displaystyle X} with values in C {\displaystyle C} is a contravariant functor
which satisfies the gluing axiom for sets in O ′ ( X ) {\displaystyle {\mathcal {O}}'(X)} . That is, on a selection of open sets of X {\displaystyle X} , F {\displaystyle {\mathcal {F}}} specifies all of the sections of a sheaf, and on the other open sets, it is undetermined.
B-sheaves are equivalent to sheaves (that is, the category of sheaves is equivalent to the category of B-sheaves). [ 1 ] Clearly a sheaf on X {\displaystyle X} can be restricted to a B-sheaf. In the other direction, given a B-sheaf F {\displaystyle {\mathcal {F}}} we must determine the sections of F {\displaystyle {\mathcal {F}}} on the other objects of O ( X ) {\displaystyle {\mathcal {O}}(X)} . To do this, note that for each open set U {\displaystyle U} , we can find a collection { B j } j ∈ J {\displaystyle \{B_{j}\}_{j\in J}} whose union is U {\displaystyle U} . Categorically speaking, this choice makes U {\displaystyle U} the colimit of the full subcategory of O ′ ( X ) {\displaystyle {\mathcal {O}}'(X)} whose objects are { B j } j ∈ J {\displaystyle \{B_{j}\}_{j\in J}} . Since F {\displaystyle {\mathcal {F}}} is contravariant, we define F ′ ( U ) {\displaystyle {\mathcal {F}}'(U)} to be the limit of the { F ( B j ) } j ∈ J {\displaystyle \{{\mathcal {F}}(B_{j})\}_{j\in J}} with respect to the restriction maps. (Here we must assume that this limit exists in C {\displaystyle C} .) If U {\displaystyle U} is a basic open set, then U {\displaystyle U} is a terminal object of the above subcategory of O ′ ( X ) {\displaystyle {\mathcal {O}}'(X)} , and hence F ′ ( U ) = F ( U ) {\displaystyle {\mathcal {F}}'(U)={\mathcal {F}}(U)} . Therefore, F ′ {\displaystyle {\mathcal {F}}'} extends F {\displaystyle {\mathcal {F}}} to a presheaf on X {\displaystyle X} . It can be verified that F ′ {\displaystyle {\mathcal {F}}'} is a sheaf, essentially because every element of every open cover of X {\displaystyle X} is a union of basis elements (by the definition of a basis), and every pairwise intersection of elements in an open cover of X {\displaystyle X} is a union of basis elements (again by the definition of a basis).
The first needs of sheaf theory were for sheaves of abelian groups ; so taking the category C {\displaystyle C} as the category of abelian groups was only natural. In applications to geometry, for example complex manifolds and algebraic geometry , the idea of a sheaf of local rings is central. This, however, is not quite the same thing; one speaks instead of a locally ringed space , because it is not true, except in trite cases, that such a sheaf is a functor into a category of local rings . It is the stalks of the sheaf that are local rings, not the collections of sections (which are rings , but in general are not close to being local ). We can think of a locally ringed space X {\displaystyle X} as a parametrised family of local rings, depending on x {\displaystyle x} in X {\displaystyle X} .
A more careful discussion dispels any mystery here. One can speak freely of a sheaf of abelian groups, or rings, because those are algebraic structures (defined, if one insists, by an explicit signature ). Any category C {\displaystyle C} having finite products supports the idea of a group object , which some prefer just to call a group in C {\displaystyle C} . In the case of this kind of purely algebraic structure, we can talk either of a sheaf having values in the category of abelian groups, or an abelian group in the category of sheaves of sets ; it really doesn't matter.
In the local ring case, it does matter. At a foundational level we must use the second style of definition, to describe what a local ring means in a category. This is a logical matter: axioms for a local ring require use of existential quantification , in the form that for any r {\displaystyle r} in the ring, one of r {\displaystyle r} and 1 − r {\displaystyle 1-r} is invertible . This allows one to specify what a 'local ring in a category' should be, in the case that the category supports enough structure.
To turn a given presheaf P {\displaystyle {\mathcal {P}}} into a sheaf F {\displaystyle {\mathcal {F}}} , there is a standard device called sheafification or sheaving . The rough intuition of what one should do, at least for a presheaf of sets, is to introduce an equivalence relation, which makes equivalent data given by different covers on the overlaps by refining the covers. One approach is therefore to go to the stalks and recover the sheaf space of the best possible sheaf F {\displaystyle {\mathcal {F}}} produced from P {\displaystyle {\mathcal {P}}} .
This use of language strongly suggests that we are dealing here with adjoint functors . Therefore, it makes sense to observe that the sheaves on X {\displaystyle X} form a full subcategory of the presheaves on X {\displaystyle X} . Implicit in that is the statement that a morphism of sheaves is nothing more than a natural transformation of the sheaves, considered as functors. Therefore, we get an abstract characterisation of sheafification as left adjoint to the inclusion. In some applications, naturally, one does need a description.
In more abstract language, the sheaves on X {\displaystyle X} form a reflective subcategory of the presheaves (Mac Lane– Moerdijk Sheaves in Geometry and Logic p. 86). In topos theory , for a Lawvere–Tierney topology and its sheaves, there is an analogous result (ibid. p. 227).
The gluing axiom of sheaf theory is rather general. One can note that the Mayer–Vietoris axiom of homotopy theory , for example, is a special case. | https://en.wikipedia.org/wiki/Gluing_axiom |
In theoretical particle physics , the gluon field strength tensor is a second order tensor field characterizing the gluon interaction between quarks .
The strong interaction is one of the fundamental interactions of nature, and the quantum field theory (QFT) to describe it is called quantum chromodynamics (QCD). Quarks interact with each other by the strong force due to their color charge , mediated by gluons. Gluons themselves possess color charge and can mutually interact.
The gluon field strength tensor is a rank 2 tensor field on the spacetime with values in the adjoint bundle of the chromodynamical SU(3) gauge group (see vector bundle for necessary definitions).
Throughout this article, Latin indices (typically a , b , c , n ) take values 1, 2, ..., 8 for the eight gluon color charges , while Greek indices (typically α , β , μ , ν ) take values 0 for timelike components and 1, 2, 3 for spacelike components of four-vectors and four-dimensional spacetime tensors. In all equations, the summation convention is used on all color and tensor indices, unless the text explicitly states that there is no sum to be taken (e.g. “no sum”).
Below the definitions (and most of the notation) follow K. Yagi, T. Hatsuda, Y. Miake [ 1 ] and Greiner, Schäfer. [ 2 ]
The tensor is denoted G , (or F , F , or some variant), and has components defined proportional to the commutator of the quark covariant derivative D μ : [ 2 ] [ 3 ]
where:
in which
Note that different authors choose different signs.
Expanding the commutator gives;
Substituting t a A α a = A α {\displaystyle t_{a}{\mathcal {A}}_{\alpha }^{a}={\mathcal {A}}_{\alpha }} and using the commutation relation [ t a , t b ] = i f a b c t c {\displaystyle [t_{a},t_{b}]=if_{ab}{}^{c}t_{c}} for the Gell-Mann matrices (with a relabeling of indices), in which f abc are the structure constants of SU(3), each of the gluon field strength components can be expressed as a linear combination of the Gell-Mann matrices as follows:
so that: [ 4 ] [ 5 ]
where again a, b, c = 1, 2, ..., 8 are color indices. As with the gluon field, in a specific coordinate system and fixed gauge G αβ are 3 × 3 traceless Hermitian matrix-valued functions, while G a αβ are real-valued functions, the components of eight four-dimensional second order tensor fields.
The gluon color field can be described using the language of differential forms , specifically as an adjoint bundle-valued curvature 2-form (note that fibers of the adjoint bundle are the su (3) Lie algebra );
where A {\displaystyle {\boldsymbol {\mathcal {A}}}} is the gluon field, a vector potential 1-form corresponding to G and ∧ is the (antisymmetric) wedge product of this algebra, producing the structure constants f abc . The Cartan -derivative of the field form (i.e. essentially the divergence of the field) would be zero in the absence of the "gluon terms", i.e. those A {\displaystyle {\boldsymbol {\mathcal {A}}}} which represent the non-abelian character of the SU(3).
A more mathematically formal derivation of these same ideas (but a slightly altered setting) can be found in the article on metric connections .
This almost parallels the electromagnetic field tensor (also denoted F ) in quantum electrodynamics , given by the electromagnetic four-potential A describing a spin-1 photon ;
or in the language of differential forms:
The key difference between quantum electrodynamics and quantum chromodynamics is that the gluon field strength has extra terms which lead to self-interactions between the gluons and asymptotic freedom . This is a complication of the strong force making it inherently non-linear , contrary to the linear theory of the electromagnetic force. QCD is a non-abelian gauge theory . The word non-abelian in group-theoretical language means that the group operation is not commutative , making the corresponding Lie algebra non-trivial.
Characteristic of field theories, the dynamics of the field strength are summarized by a suitable Lagrangian density and substitution into the Euler–Lagrange equation (for fields) obtains the equation of motion for the field . The Lagrangian density for massless quarks, bound by gluons, is: [ 2 ]
where "tr" denotes trace of the 3 × 3 matrix G αβ G αβ , and γ μ are the 4 × 4 gamma matrices . In the fermionic term i ψ ¯ ( i D μ ) γ μ ψ {\displaystyle i{\bar {\psi }}\left(iD_{\mu }\right)\gamma ^{\mu }\psi } , both color and spinor indices are suppressed. With indices explicit, ψ i , α {\displaystyle \psi _{i,\alpha }} where i = 1 , … , 3 {\displaystyle i=1,\ldots ,3} are color indices and α = 1 , … , 4 {\displaystyle \alpha =1,\ldots ,4} are Dirac spinor indices.
In contrast to QED, the gluon field strength tensor is not gauge invariant by itself. Only the product of two contracted over all indices is gauge invariant.
Treated as a classical field theory, the equations of motion for the [ 1 ] quark fields are:
which is like the Dirac equation , and the equations of motion for the gluon (gauge) fields are:
which are similar to the Maxwell equations (when written in tensor notation). More specifically, these are the Yang–Mills equations for quark and gluon fields. The color charge four-current is the source of the gluon field strength tensor, analogous to the electromagnetic four-current as the source of the electromagnetic tensor. It is given by
which is a conserved current since color charge is conserved. In other words, the color four-current must satisfy the continuity equation : | https://en.wikipedia.org/wiki/Gluon_field_strength_tensor |
Glutamate-1-semialdehyde is a molecule formed from by the reduction of tRNA bound glutamate , catalyzed by glutamyl-tRNA reductase . It is isomerized by glutamate-1-semialdehyde 2,1-aminomutase to give aminolevulinic acid in the biosynthesis of porphyrins , including heme and chlorophyll . [ 1 ] [ 2 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glutamate-1-semialdehyde |
A genetically engineered fluorescent protein that changes its fluorescence when bound to the neurotransmitter glutamate . [ 1 ] Glutamate-sensitive fluorescent reporters (iGluSnFR, colloquially pronounced ' glue sniffer ') are used to monitor the activity of presynaptic terminals by fluorescence microscopy . GluSnFRs are a class of optogenetic sensors used in neuroscience research. [ 2 ] In brain tissue, two-photon microscopy is typically used to monitor GluSnFR fluorescence.
The widely used iGluSnFR consists of a circularly permuted enhanced green fluorescent protein (cpEGFP) fused to a glutamate binding protein (GluBP) from a bacterium . [ 3 ] When GluBP binds a glutamate molecule, it changes its shape, pulling the EGFP barrel together, increasing fluorescence. A specific peptide segment ( PDGFR ) is included to bring the sensor to the outside of the cell membrane . [ 4 ] In the more recent version by Aggarwal et al. (2022), [ 1 ] researchers introduced iGluSnFR to two additional anchoring domains, a glycosylphostidylinositol (GPI) anchor, and a modified form of the cytosolic -cterminal domain of Stargazin with a PDZ ligand.
The first genetically encoded fluorescent glutamate sensors (FLIPE, GluSnFR and SuperGluSnFR) were constructed by attaching cyan-fluorescent protein (CFP) and yellow-fluorescent protein (YFP) to a bacterial glutamate binding protein (GluBP). [ 5 ] [ 6 ] Glutamate binding changed the distance between CFP and YFP, changing the efficiency of energy transfer ( FRET ) between the two fluorophores . [ 7 ] [ 8 ] A breakthrough in visualizing glutamate release was achieved with iGluSnFR, a single-fluorophore glutamate sensor based on EGFP producing a ~5‑fold increase in fluorescence. [ 3 ] To measure synaptic transmission at high frequencies, novel iGluSnFR variants with accelerated kinetics have recently been developed. [ 9 ] [ 10 ] | https://en.wikipedia.org/wiki/Glutamate-sensitive_fluorescent_reporter |
Glutamatergic means "related to glutamate ". A glutamatergic agent (or drug ) is a chemical that directly modulates the excitatory amino acid ( glutamate / aspartate ) system in the body or brain. Examples include excitatory amino acid receptor agonists , excitatory amino acid receptor antagonists , and excitatory amino acid reuptake inhibitors .
This drug article relating to the nervous system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glutamatergic |
In biochemistry , the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system . [ 1 ] Neurons are unable to synthesize either the excitatory neurotransmitter glutamate , or the inhibitory GABA from glucose . Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes . The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes (non-neuronal glial cells ). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA. [ 2 ]
Initially, in a glutamatergic synapse, the neurotransmitter glutamate is released from the neurons and is taken up into the synaptic cleft. Glutamate residing in the synapse must be rapidly removed in one of three ways:
Postsynaptic neurons remove little glutamate from the synapse. There is active reuptake into presynaptic neurons, but this mechanism appears to be less important than astrocytic transport. Astrocytes could dispose of transported glutamate in two ways. They could export it to blood capillaries, which abut the astrocyte foot processes. However, this strategy would result in a net loss of carbon and nitrogen from the system. An alternate approach would be to convert glutamate into another compound, preferably a non-neuroactive species. The advantage of this approach is that neuronal glutamate could be restored without the risk of trafficking the transmitter through extracellular fluid, where glutamate would cause neuronal depolarization. Astrocytes readily convert glutamate to glutamine via the glutamine synthetase pathway and released into the extracellular space. [ 3 ] The glutamine is taken into the presynaptic terminals and metabolized into glutamate by the phosphate-activated glutaminase (a mitochondrial enzyme ). The glutamate that is synthesized in the presynaptic terminal is packaged into synaptic vesicles by the glutamate transporter, VGLUT . Once the vesicle is released, glutamate is removed from the synaptic cleft by excitatory amino-acid transporters (EAATs). This allows synaptic terminals and glial cells to work together to maintain a proper supply of glutamate, which can also be produced by transamination of 2-oxoglutarate , an intermediate in the citric acid cycle . [ 1 ] Recent electrophysiological evidence suggests that active synapses require presynaptically localized glutamine glutamate cycle to maintain excitatory neurotransmission in specific circumstances. [ 4 ] In other systems, it has been suggested that neurons have alternate mechanisms to cope with compromised glutamate–glutamine cycling. [ 5 ]
At GABAergic synapses, the cycle is called the GABA-glutamine cycle. Here the glutamine taken up by neurons is converted to glutamate, which is then metabolized into GABA by glutamate decarboxylase (GAD). Upon release, GABA is taken up into astrocytes via GABA transporters and then catabolized into succinate by the joint actions of GABA transaminase and succinate-semialdehyde dehydrogenase . Glutamine is synthesized from succinate via the TCA cycle, which includes a condensation reaction of oxaloacetate and acetyl-CoA -forming citrate . Then the synthesis of α-ketoglutarate and glutamate occurs, after which glutamate is again metabolized into GABA by GAD. The supply of glutamine to GABAergic neurons is less significant, because these neurons exhibit a larger proportion of reuptake of the released neurotransmitter compared to their glutamatergic counterparts [ 6 ]
One of the problems of both the glutamate–glutamine cycle and the GABA-glutamine cycle is ammonia homeostasis . When one molecule of glutamate or GABA is converted to glutamine in the astrocytes, one molecule of ammonia is absorbed. Also, for each molecule of glutamate or GABA cycled into the astrocytes from the synapse, one molecule of ammonia will be produced in the neurons. This ammonia will obviously have to be transported out of the neurons and back into the astrocytes for detoxification, as an elevated ammonia concentration has detrimental effects on a number of cellular functions and can cause a spectrum of neuropsychiatric and neurological symptoms (impaired memory, shortened attention span, sleep-wake inversions, brain edema, intracranial hypertension, seizures, ataxia and coma). [ 7 ]
This could happen in two different ways: ammonia itself might simply diffuse (as NH3) or be transported (as NH4+) across the cell membranes in and out of the extracellular space, or a shuttle system involving carrier molecules ( amino acids ) might be employed. Certainly, ammonia can diffuse across lipid membranes, and it has been shown that ammonia can be transported by K+/Cl− co-transporters. [ 2 ]
Since diffusion and transport of free ammonia across the cell membrane will affect the pH level of the cell, the more attractive and regulated way of transporting ammonia between the neuronal and the astrocytic compartment is via an amino-acid shuttle, of which there are two: leucine and alanine . The amino acid moves in the opposite direction of glutamine. In the opposite direction of the amino acid, a corresponding molecule is transported; for alanine this molecule is lactate ; for leucine, α-ketoisocaproate .
The ammonia fixed as part of the glutamate dehydrogenase enzyme reaction in the neurons is transaminated into α-ketoisocaproate to form the branched-chain amino acid leucine , which is exported to the astrocytes, where the process is reversed. α-ketoisocaproate is transported in the other direction.
The ammonia produced in neurons is fixed into α-ketoglutarate by the glutamate-dehydrogenase reaction to form glutamate, then transaminated by alanine aminotransferase into lactate-derived pyruvate to form alanine, which is exported to astrocytes. In the astrocytes, this process is then reversed, and lactate is transported in the other direction.
Numerous reports have been published indicating that the glutamate/GABA–glutamine cycle is compromised in a variety of neurological disorders and conditions. Biopsies of sclerotic hippocampus tissue from human subjects with epilepsy have shown decreased glutamate–glutamine cycling. Another pathology in which the glutamate/GABA–glutamine cycle might be compromised is Alzheimer's disease ; NMR spectroscopy showed decreased glutamate neurotransmission activity and TCA cycling rate in patients with Alzheimer's disease. Hyperammonemia in the brain, typically occurring as a secondary complication of primary liver disease and known as hepatic encephalopathy , is a condition that affects glutamate/GABA–glutamine cycling in the brain. [ 2 ] Current research into autism also indicates potential roles for glutamate, glutamine, and/or GABA in autistic spectrum disorders. [ 8 ]
In the treatment of epilepsy , drugs such as vigabatrin that target both GABA transporters and the GABA metabolizing enzyme GABA-transaminase have been marketed, providing proof of principle for the neurotransmitter cycling systems as pharmacological targets. However, with regard to glutamate transport and metabolism, no such drugs have been developed, because glutamatergic synapses are abundant, and the neurotransmitter glutamate is an important metabolite in metabolism, making interference capable of adverse effects. So far, most of the drug development directed at the glutamatergic system seems to have been focused on ionotropic glutamate receptors as pharmacological targets, although G-protein coupled receptors have been attracting increased attention over the years. [ 9 ] | https://en.wikipedia.org/wiki/Glutamate–glutamine_cycle |
Glutaminolysis ( glutamine + -lysis ) is a series of biochemical reactions by which the amino acid glutamine is lysed to glutamate , aspartate , CO 2 , pyruvate , lactate , alanine and citrate . [ 1 ] [ 2 ]
Glutaminolysis partially recruits reaction steps from the citric acid cycle and the malate-aspartate shuttle .
The conversion of the amino acid glutamine to α-ketoglutarate takes place in two reaction steps:
1. Hydrolysis of the amino group of glutamine yielding glutamate and ammonium .
Catalyzing enzyme: glutaminase (EC 3.5.1.2)
2. Glutamate can be excreted or can be further metabolized to α-ketoglutarate.
For the conversion of glutamate to α-ketoglutarate three different reactions are possible:
Catalyzing enzymes:
catalyzing enzyme: α-ketoglutarate dehydrogenase complex
catalyzing enzyme: succinyl-CoA-synthetase, EC 6.2.1.4
catalyzing enzyme: succinate dehydrogenase , EC 1.3.5.1
catalyzing enzyme: fumarase , EC 4.2.1.2
catalyzing enzyme: malate dehydrogenase , EC 1.1.1.37 (component of the malate aspartate shuttle)
catalyzing enzyme: citrate synthase , EC 2.3.3.1
The conversion of malate to pyruvate and lactate is catalyzed by
according to the following equations:
The reactions of the glutaminolytic pathway take place partly in the mitochondria and to some extent in the cytosol (compare the metabolic scheme of the glutaminolytic pathway).
Glutaminolysis takes place in all proliferating cells, [ 3 ] such as lymphocytes , thymocytes , colonocytes, adipocytes and especially in tumor cells. [ 1 ] Glutaminolysis has been targeted for therapeutic purposes. [ 4 ] In tumor cells the citric acid cycle is truncated due to an inhibition of the enzyme aconitase (EC 4.2.1.3) by high concentrations of reactive oxygen species (ROS) [ 5 ] [ 6 ] Aconitase catalyzes the conversion of citrate to isocitrate.
On the other hand, tumor cells over express phosphate dependent glutaminase and NAD(P)-dependent malate decarboxylase, [ 7 ] [ 8 ] [ 9 ] [ 10 ] which in combination with the remaining reaction steps of the citric acid cycle from α-ketoglutarate to citrate impart the possibility of a new energy producing pathway, the degradation of the amino acid glutamine to glutamate, aspartate, pyruvate CO 2 , lactate and citrate.
Besides glycolysis in tumor cells glutaminolysis is another main pillar for energy production. High extracellular glutamine concentrations stimulate tumor growth and are essential for cell transformation. [ 9 ] [ 11 ] On the other hand, a reduction of glutamine correlates with phenotypical and functional differentiation of the cells. [ 12 ]
Due to low glutamate dehydrogenase and glutamate pyruvate transaminase activities, in tumor cells the conversion of glutamate to alpha-ketoglutarate mainly takes place via glutamate oxaloacetate transaminase. [ 13 ] | https://en.wikipedia.org/wiki/Glutaminolysis |
Glutaryl-coenzyme A is an intermediate in the metabolism of lysine and tryptophan . [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glutaryl-CoA |
The ascorbate-glutathione cycle , sometimes Foyer - Halliwell - Asada pathway , is a metabolic pathway that detoxifies hydrogen peroxide (H 2 O 2 ), a reactive oxygen species that is produced as a waste product in metabolism . The cycle involves the antioxidant metabolites: ascorbate , glutathione and NADPH and the enzymes linking these metabolites. [ 1 ]
In the first step of this pathway, H 2 O 2 is reduced to water by ascorbate peroxidase (APX) using ascorbate (ASC) as the electron donor. The oxidized ascorbate (monodehydroascorbate, MDA) is regenerated by monodehydroascorbate reductase (MDAR). [ 2 ] However, monodehydroascorbate is a radical and if not rapidly reduced it disproportionates into ascorbate and dehydroascorbate (DHA). Dehydroascorbate is reduced to ascorbate by dehydroascorbate reductase (DHAR) at the expense of GSH , yielding oxidized glutathione ( GSSG ). Finally GSSG is reduced by glutathione reductase (GR) using NADPH as the electron donor. Thus ascorbate and glutathione are not consumed; the net electron flow is from NADPH to H 2 O 2 . The reduction of dehydroascorbate may be non-enzymatic or catalysed by proteins with dehydroascorbate reductase activity, such as glutathione S -transferase omega 1 or glutaredoxins . [ 3 ] [ 4 ]
In plants , the glutathione-ascorbate cycle operates in the cytosol , mitochondria , plastids and peroxisomes . [ 5 ] [ 6 ] Since glutathione, ascorbate and NADPH are present in high concentrations in plant cells it is assumed that the glutathione-ascorbate cycle plays a key role for H 2 O 2 detoxification. Nevertheless, other enzymes ( peroxidases ) including peroxiredoxins and glutathione peroxidases , which use thioredoxins or glutaredoxins as reducing substrates, also contribute to H 2 O 2 removal in plants. [ 7 ] | https://en.wikipedia.org/wiki/Glutathione-ascorbate_cycle |
Glycal is a name for cyclic enol ether derivatives of sugars having a double bond between carbon atoms 1 and 2 of the ring. The term "glycal" should not be used for an unsaturated sugar that has a double bond in any position other than between carbon atoms 1 and 2. [ 1 ]
The first glycal was synthesized by Hermann Emil Fischer and Karl Zach in 1913. [ 2 ] They synthesized this 1,2-unsaturated sugar from D- glucose and named their product D-glucal. Fischer believed he had synthesized an aldehyde , and therefore he gave the product a name that suggested this. [ 3 ] By the time he discovered his mistake, the name "glycal" was adopted as a general name for all sugars with a double bond between carbon atoms 1 and 2. [ 4 ]
Glycals can be formed as pyranose (six-membered) or furanose (five-membered) rings, depending on the monosaccharide used as a starting material to synthesize the glycal. Glycals can also be classified as endo -glycals or exo -glycals. A glycal is an endo-glycal when the double bond is within the ring. If the hydroxyl group on carbon 1 has been replaced with another carbon atom, a double bond can also form outside the ring between carbon 1 and this new carbon. In this case, the product is called an exo -glycal. [ 5 ] The glycal conformation that has been studied in most depth is that of the pyranose endo -glycal. The favoured conformation of this glycal is the half-chair, [ 6 ] a result which has been confirmed by quantum mechanical calculations. [ 7 ]
The original Fischer glycal synthesis was the reductive elimination with zinc of a glycosyl halide. This glycosyl halide was formed from a monosaccharide starting material. [ 8 ] Some other synthetic routes include:
A general example of each synthetic route is given below (drawn with first discussed synthesis bottom right, moving clockwise):
The double bond of a glycal allows many other functional groups to be introduced into a monosaccharide. Like an alkene , a glycal can undergo electrophilic addition across the double bond to add in these new atoms such as halogens , epoxides , and nitrogen. The glycal double bond also allows a deoxy position (carbon in the ring that doesn’t have an oxygen bonded to it) to be easily introduced. [ 8 ]
Glycals have many uses in synthetic carbohydrate chemistry. They are commonly used as glycosylation donors, meaning that they can react with other monosaccharides to form a longer chain of monosaccharides called an oligosaccharide. [ 11 ]
Glycals can also have interesting applications in studying biological systems, particularly enzymes. D-glucal and radiolabelled D-galactal have been used to selectively bind with amino acids in the active sites of several enzymes. These enzyme-glycal complexes allow these amino acids that are essential for catalysis to be identified and allow for a better understanding of how these enzymes function. [ 12 ] | https://en.wikipedia.org/wiki/Glycal |
The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically ". [ 1 ] However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate , such as a glycoprotein , glycolipid , or a proteoglycan , even if the carbohydrate is only an oligosaccharide . [ 2 ] Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan (or, to be more specific, a glucan ) composed of β-1,4-linked D -glucose, and chitin is a glycan composed of β-1,4-linked N -acetyl- D -glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.
Glycans can be found attached to proteins as in glycoproteins and proteoglycans. In general, they are found on the exterior surface of cells. O- and N-linked glycans are very common in eukaryotes but may also be found, although less commonly, in prokaryotes .
N-Linked glycans are attached in the endoplasmic reticulum to the nitrogen (N) in the side chain of asparagine (Asn) in the sequon . The sequon is an Asn-X-Ser or Asn-X-Thr sequence, where X is any amino acid except proline and the glycan may be composed of N -acetylgalactosamine , galactose , neuraminic acid , N -acetylglucosamine , fucose , mannose , and other monosaccharides.
In eukaryotes, N-linked glycans are derived from a core 14- sugar unit assembled in the cytoplasm and endoplasmic reticulum . First, two N -acetylglucosamine residues are attached to dolichol monophosphate , a lipid, on the external side of the endoplasmic reticulum membrane. Five mannose residues are then added to this structure. At this point, the partially finished core glycan is flipped across the endoplasmic reticulum membrane, so that it is now located within the reticular lumen. Assembly then continues within the endoplasmic reticulum, with the addition of four more mannose residues. Finally, three glucose residues are added to this structure. Following full assembly, the glycan is transferred en bloc by the glycosyltransferase oligosaccharyltransferase to a nascent peptide chain, within the reticular lumen. This core structure of N-linked glycans, thus, consists of 14 residues (3 glucose, 9 mannose, and 2 N -acetylglucosamine).
Image: https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.figgrp.469
Dark squares are N -acetylglucosamine; light circles are mannose; dark triangles are glucose.
Once transferred to the nascent peptide chain, N-linked glycans, in general, undergo extensive processing reactions, whereby the three glucose residues are removed, as well as several mannose residues, depending on the N-linked glycan in question. The removal of the glucose residues is dependent on proper protein folding. These processing reactions occur in the Golgi apparatus . Modification reactions may involve the addition of a phosphate or acetyl group onto the sugars, or the addition of new sugars, such as neuraminic acid . Processing and modification of N-linked glycans within the Golgi does not follow a linear pathway. As a result, many different variations of N-linked glycan structure are possible, depending on enzyme activity in the Golgi.
N-linked glycans are extremely important in proper protein folding in eukaryotic cells. Chaperone proteins in the endoplasmic reticulum, such as calnexin and calreticulin , bind to the three glucose residues present on the core N-linked glycan. These chaperone proteins then serve to aid in the folding of the protein that the glycan is attached to. Following proper folding, the three glucose residues are removed, and the glycan moves on to further processing reactions. If the protein fails to fold properly, the three glucose residues are reattached, allowing the protein to re-associate with the chaperones. This cycle may repeat several times until a protein reaches its proper conformation. If a protein repeatedly fails to properly fold, it is excreted from the endoplasmic reticulum and degraded by cytoplasmic proteases.
N-linked glycans also contribute to protein folding by steric effects. For example, cysteine residues in the peptide may be temporarily blocked from forming disulfide bonds with other cysteine residues, due to the size of a nearby glycan. Therefore, the presence of a N-linked glycan allows the cell to control which cysteine residues will form disulfide bonds.
N-linked glycans also play an important role in cell-cell interactions. For example, tumour cells make N-linked glycans that are abnormal. These are recognized by the CD337 receptor on Natural Killer cells as a sign that the cell in question is cancerous.
Within the immune system the N-linked glycans on an immune cell's surface will help dictate that migration pattern of the cell, e.g. immune cells that migrate to the skin have specific glycosylations that favor homing to that site. [ 3 ] The glycosylation patterns on the various immunoglobulins including IgE, IgM, IgD, IgE, IgA, and IgG bestow them with unique effector functions by altering their affinities for Fc and other immune receptors. [ 3 ] Glycans may also be involved in "self" and "non self" discrimination, which may be relevant to the pathophysiology of various autoimmune diseases; [ 3 ] including rheumatoid arthritis [ 4 ] and type 1 diabetes. [ 5 ]
The targeting of degradative lysosomal enzymes is also accomplished by N-linked glycans. The modification of an N-linked glycan with a mannose-6-phosphate residue serves as a signal that the protein to which this glycan is attached should be moved to the lysosome. This recognition and trafficking of lysosomal enzymes by the presence of mannose-6-phosphate is accomplished by two proteins: CI-MPR (cation-independent mannose-6-phosphate receptor ) and CD-MPR (cation-dependent mannose-6-phosphate receptor).
In eukaryotes, O -linked glycans are assembled one sugar at a time on a serine or threonine residue of a peptide chain in the Golgi apparatus. Unlike N -linked glycans, there is no known consensus sequence yet. However, the placement of a proline residue at either -1 or +3 relative to the serine or threonine is favourable for O-linked glycosylation.
The first monosaccharide attached in the synthesis of O -linked glycans is N-acetyl-galactosamine. After this, several different pathways are possible. A Core 1 structure is generated by the addition of galactose. A Core 2 structure is generated by the addition of N-acetyl-glucosamine to the N-acetyl-galactosamine of the Core 1 structure. Core 3 structures are generated by the addition of a single N-acetyl-glucosamine to the original N-acetyl-galactosamine. Core 4 structures are generated by the addition of a second N-acetyl-glucosamine to the Core 3 structure. Other core structures are possible, though less common.
Images:
https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.figgrp.561 : Core 1 and Core 2 generation. White square = N-acetyl-galactosamine; black circle = galactose; Black square = N-acetyl-glucosamine. Note: There is a mistake in this diagram. The bottom square should always be white in each image, not black.
https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.figgrp.562 : Core 3 and Core 4 generation.
A common structural theme in O-linked glycans is the addition of polylactosamine units to the various core structures. These are formed by the repetitive addition of galactose and N-acetyl-glucosamine units. Polylactosamine chains on O-linked glycans are often capped by the addition of a sialic acid residue (similar to neuraminic acid). If a fucose residue is also added, to the next to penultimate residue, a Sialyl-Lewis X (SLex) structure is formed.
Sialyl lewis x is important in ABO blood antigen determination.
SLex is also important to proper immune response. P- selectin release from Weibel-Palade bodies , on blood vessel endothelial cells, can be induced by a number of factors. One such factor is the response of the endothelial cell to certain bacterial molecules, such as peptidoglycan . P-selectin binds to the SLex structure that is present on neutrophils in the bloodstream and helps to mediate the extravasation of these cells into the surrounding tissue during infection.
O -linked glycans, in particular mucin , have been found to be important in developing normal intestinal microflora. Certain strains of intestinal bacteria bind specifically to mucin, allowing them to colonize the intestine.
Examples of O -linked glycoproteins are:
Another type of cellular glycan is the glycosaminoglycans (GAGs). These comprise 2-aminosugars linked in an alternating fashion with uronic acids , and include polymers such as heparin , heparan sulfate , chondroitin , keratan and dermatan . Some glycosaminoglycans, such as heparan sulfate, are found attached to the cell surface, where they are linked through a tetrasacharide linker via a xylosyl residue to a protein (forming a glycoprotein or proteoglycan ).
A 2012 report from the U.S. National Research Council calls for a new focus on glycoscience, a field that explores the structures and functions of glycans and promises great advances in areas as diverse as medicine, energy generation, and materials science. [ 6 ] Until now, glycans have received little attention from the research community due to a lack of tools to probe their often complex structures and properties. [ 7 ] The report presents a roadmap for transforming glycoscience from a field dominated by specialists to a widely studied and integrated discipline. As of 2019, NHLBI has established a new national career development consortium for excellence in glycoscience, led by program director Karin Hoffmeister . [ 8 ]
The following are examples of the commonly used techniques in glycan analysis: [ 9 ] [ 10 ]
The most commonly applied methods are MS and HPLC , in which the glycan part is cleaved either enzymatically or chemically from the target and subjected to analysis. [ 11 ] In case of glycolipids, they can be analyzed directly without separation of the lipid component.
N- glycans from glycoproteins are analyzed routinely by high-performance-liquid-chromatography (reversed phase, normal phase and ion exchange HPLC) after tagging the reducing end of the sugars with a fluorescent compound (reductive labeling). [ 12 ] A large variety of different labels were introduced in the recent years, where 2-aminobenzamide (AB), anthranilic acid (AA), 2-aminopyridin (PA), 2-aminoacridone (AMAC) and 3-(acetylamino)-6-aminoacridine (AA-Ac) are just a few of them. [ 13 ] Different labels have to be used for different ESI modes and MS systems used. [ 14 ]
O- glycans are usually analysed without any tags, due to the chemical release conditions preventing them to be labeled.
Fractionated glycans from high-performance liquid chromatography (HPLC) instruments can be further analyzed by MALDI -TOF-MS(MS) to get further information about structure and purity. Sometimes glycan pools are analyzed directly by mass spectrometry without prefractionation, although a discrimination between isobaric glycan structures is more challenging or even not always possible. Anyway, direct MALDI -TOF-MS analysis can lead to a fast and straightforward illustration of the glycan pool. [ 15 ]
In recent years, high performance liquid chromatography online coupled to mass spectrometry became very popular. By choosing porous graphitic carbon as a stationary phase for liquid chromatography, even non derivatized glycans can be analyzed. Detection is here done by mass spectrometry, but in instead of MALDI -MS, electrospray ionisation ( ESI ) is more frequently used. [ 16 ] [ 17 ] [ 18 ]
Although MRM has been used extensively in metabolomics and proteomics, its high sensitivity and linear response over a wide dynamic range make it especially suited for glycan biomarker research and discovery. MRM is performed on a triple quadrupole (QqQ) instrument, which is set to detect a predetermined precursor ion in the first quadrupole, a fragmented in the collision quadrupole, and a predetermined fragment ion in the third quadrupole. It is a non-scanning technique, wherein each transition is detected individually and the detection of multiple transitions occurs concurrently in duty cycles. This technique is being used to characterize the immune glycome. [ 3 ] [ 19 ]
Table 1 :Advantages and disadvantages of mass spectrometry in glycan analysis
Lectin and antibody arrays provide high-throughput screening of many samples containing glycans. This method uses either naturally occurring lectins or artificial monoclonal antibodies , where both are immobilized on a certain chip and incubated with a fluorescent glycoprotein sample.
Glycan arrays, like that offered by the Consortium for Functional Glycomics and Z Biotech LLC , contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands.
Metabolic labeling of glycans can be used as a way to detect glycan structures. A well-known strategy involves the use of azide -labeled sugars which can be reacted using the Staudinger ligation . This method has been used for in vitro and in vivo imaging of glycans.
X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy for complete structural analysis of complex glycans is a difficult and complex field. However, the structure of the binding site of numerous lectins , enzymes and other carbohydrate-binding proteins have revealed a wide variety of the structural basis for glycome function. The purity of test samples have been obtained through chromatography ( affinity chromatography etc.) and analytical electrophoresis ( PAGE (polyacrylamide electrophoresis) , capillary electrophoresis , affinity electrophoresis , etc.). | https://en.wikipedia.org/wiki/Glycan |
Glycan-Protein interactions represent a class of biomolecular interactions that occur between free or protein-bound glycans and their cognate binding partners. Intramolecular glycan-protein (protein-glycan) interactions occur between glycans and proteins that they are covalently attached to. Together with protein-protein interactions , they form a mechanistic basis for many essential cell processes, especially for cell-cell interactions and host-cell interactions. [ 2 ] For instance, SARS-CoV-2 , the causative agent of COVID-19 , employs its extensively glycosylated spike (S) protein to bind to the ACE2 receptor, allowing it to enter host cells. [ 3 ] The spike protein is a trimeric structure, with each subunit containing 22 N-glycosylation sites, making it an attractive target for vaccine search. [ 3 ] [ 4 ]
Glycosylation, i.e., the addition of glycans (a generic name for monosaccharides and oligosaccharides ) to a protein, is one of the major post-translational modification of proteins contributing to the enormous biological complexity of life. Indeed, three different hexoses could theoretically produce from 1056 to 27,648 unique trisaccharides in contrast to only 6 peptides or oligonucleotides formed from 3 amino acids or 3 nucleotides respectively. [ 2 ] In contrast to template-driven protein biosynthesis , the "language" of glycosylation is still unknown, making glycobiology a hot topic of current research given their prevalence in living organisms. [ 2 ]
The study of glycan-protein interactions provides insight into the mechanisms of cell-signaling and allows to create better-diagnosing tools for many diseases, including cancer . Indeed, there are no known types of cancer that do not involve erratic patterns of protein glycosylation . [ 5 ]
The binding of glycan-binding proteins (GBPs) to glycans could be modeled with simple equilibrium . Denoting glycans as G {\displaystyle G} and proteins as P {\displaystyle P} :
P r o t e i n ( P ) + G l y c a n ( G ) ⇌ P G {\displaystyle Protein(P)+Glycan(G)\rightleftharpoons PG}
With an associated equilibrium constant of
K a = [ P G ] [ P ] [ G ] {\displaystyle K_{a}={\frac {[PG]}{[P][G]}}}
Which is rearranged to give dissociation constant K d {\displaystyle K_{d}} following biochemical conventions:
K d = [ P ] [ G ] [ P G ] {\displaystyle K_{d}={\frac {[P][G]}{[PG]}}}
Given that many GBPs exhibit multivalency, this model may be expanded to account for multiple equilibria:
P + G ⇌ P G {\displaystyle P+G\rightleftharpoons PG}
P G + G ⇌ P G 2 {\displaystyle PG+G\rightleftharpoons PG_{2}}
… {\displaystyle \dots }
P G n − 1 + G ⇌ P G n {\displaystyle PG_{n-1}+G\rightleftharpoons PG_{n}}
Denoting cumulative equilibrium of binding with i {\displaystyle i} ligands as
P + i G ⇌ P G i {\displaystyle P+iG\rightleftharpoons PG_{i}}
With corresponding equilibrium constant:
β i = [ P G i ] [ P ] [ G ] i {\displaystyle \beta _{i}={\frac {[PG_{i}]}{[P][G]^{i}}}}
And writing material balance for protein ( c P {\displaystyle c_{P}} denotes the total concentration of protein):
c P = [ P ] + [ P G ] + ⋯ + [ P G n ] {\displaystyle c_{P}=[P]+[PG]+\dots +[PG_{n}]}
Expressing the terms through an equilibrium constant, a final result is found:
c P = [ P ] ( 1 + β 1 [ G ] + ⋯ + β n [ G ] n {\displaystyle c_{P}=[P](1+\beta _{1}[G]+\dots +\beta _{n}[G]^{n}}
The concentration of free protein is, thus:
[ P ] = c P 1 + ∑ i = 1 n β i [ G ] i {\displaystyle [P]={\frac {c_{P}}{1+\sum _{i=1}^{n}{\beta _{i}[G]^{i}}}}}
If n = 1 {\displaystyle n=1} , i.e. there is only one carbohydrate receptor domain, the equation reduces to
[ P ] = c P 1 + β 1 [ G ] {\displaystyle [P]={\frac {c_{P}}{1+\beta _{1}[G]}}}
With increasing i {\displaystyle i} the concentration of free protein decreases; hence, the apparent K D {\displaystyle K_{D}} decreases too.
The chemical intuition suggests that the glycan-binding sites may be enriched in polar amino acid residues that form non-covalent interactions , such as hydrogen bonds , with polar carbohydrates. Indeed, a statistical analysis of carbohydrate-binding pockets shows that aspartic acid and asparagine residues are present twice as often as would be predicted by chance. [ 6 ] Surprisingly, there is an even stronger preference for aromatic amino acids : tryptophan has a 9-fold increase in prevalence, tyrosine a 3-fold one, and histidine a 2-fold increase. It has been shown that the underlying force is the C H − π {\displaystyle CH-\pi } interaction between the aromatic π {\displaystyle \pi } system and the C − H {\displaystyle C-H} in carbohydrate as shown in Figure 1 . The C H − π {\displaystyle CH-\pi } interaction is identified if the θ ⩽ 40 {\displaystyle \theta \leqslant 40} °, the C H − π {\displaystyle CH-\pi } distance (distance from C {\displaystyle C} to X {\displaystyle X} ) is less than 4.5Å. [ 6 ]
This C H − π {\displaystyle CH-\pi } interaction strongly depends on the stereochemistry of the carbohydrate molecule. For example, consider the top ( β {\displaystyle \beta } ) and bottom ( α {\displaystyle \alpha } ) faces of β {\displaystyle \beta } -D-Glucose and β {\displaystyle \beta } -D-Galactose . It has been shown that a single change in the stereochemistry at C4 carbon shifts preference for aromatic residues from β {\displaystyle \beta } side (2.7 fold preference for glucose) to the α {\displaystyle \alpha } side (14 fold preference for galactose). [ 6 ]
The comparison of electrostatic surface potentials (ESPs) of aromatic rings in tryptophan , tyrosine , phenylalanine , and histidine suggests that electronic effects also play a role in the binding to glycans (see Figure 2 ). After normalizing the electron densities for surface area, the tryptophan still remains the most electron rich acceptor of C H − π {\displaystyle CH-\pi } interactions, suggesting a possible reason for its 9-fold prevalence in carbohydrate binding pockets. [ 6 ] Overall, the electrostatic potential maps follow the prevalence trend of Trp >> Tyr > ( Phe ) > His {\displaystyle {\ce {Trp >> Tyr > (Phe) > His}}} .
There are many proteins capable of binding to glycans, including lectins , antibodies , microbial adhesins , viral agglutinins , etc.
Lectins is a generic name for proteins with carbohydrate-recognizing domains (CRD). Although it became almost synonymous with glycan-binding proteins, it does not include antibodies which also belong to the class.
Lectins found in plants and fungi cells have been extensively used in research as a tool to detect, purify, and analyze glycans. However, useful lectins usually have sub-optimal specificities . For instance, Ulex europaeus agglutinin-1 (UEA-1), a plant-extracted lectin capable of binding to human blood type O antigen , can also bind to unrelated glycans such as 2'-fucosyllactose, GalNAcα1-4(Fucα1-2)Galβ1-4GlcNAc, and Lewis-Y antigen. [ 7 ]
Although antibodies exhibit nanomolar affinities toward protein antigens, the specificity against glycans is very limited. [ 8 ] In fact, available antibodies may bind only <4% of the 7000 mammalian glycan antigens; moreover, most of those antibodies have low affinity and exhibit cross-reactivity. [ 9 ] [ 7 ]
In contrast with jawed vertebrates whose immunity is based on variable, diverse, and joining gene segments (VDJs) of immunoglobulins , the jawless invertebrates , such as lamprey and hagfish , create a receptor diversity by somatic DNA rearrangement of leucine -rich repeat (LRR) modules that are incorporate in *vlr* genes (variable leukocyte receptors). [ 10 ] Those LRR form 3D structures resembling curved solenoids that selectively bind specific glycans. [ 11 ]
A study from University of Maryland has shown that lamprey antibodies (lambodies) could selectively bind to tumor -associated carbohydrate antigens (such as Tn and TF α {\displaystyle \alpha } ) at nanomolar affinities. [ 9 ] The T-nouvelle antigen (Tn) and TF α {\displaystyle \alpha } are present in proteins in as much as 90% of different cancer cells after post-translational modification , whereas in healthy cells those antigens are much more complex. A selection of lambodies that could bind to aGPA , a human erythrocyte membrane glycoprotein that is covered with 16 TF α {\displaystyle \alpha } moieties, through magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS) has yielded a leucine-rich lambody VLRB.aGPA.23 . This lambody selectively stained (over healthy samples) cells from 14 different types of adenocarcinomas : bladder , esophagus , ovary , tongue , cheek, cervix , liver , nose, nasopharynx , greater omentum, colon , breast , larynx , and lung . [ 9 ] Moreover, patients whose tissues stained positive with VLRB.aGPA.23 had a significantly smaller survival rate. [ 9 ]
A close look at the crystal structure of VLRB.aGPA.23 reveals a tryptophan residue at position 187 right over the carbohydrate binding pocket. [ 12 ]
Many glycan binding proteins (GBPs) are oligomeric and typically contain multiple sites for glycan binding (also called carbohydrate-recognition domains). The ability to form multivalent protein- ligand interactions significantly enhances the strength of binding: while K D {\displaystyle K_{D}} values for individual CRD-glycan interactions may be in the mM range, the overall affinity of GBP towards glycans may reach nanomolar or even picomolar ranges. The overall strength of interactions is described as avidity K D {\displaystyle K_{D}} (in contrast with an affinity K D {\displaystyle K_{D}} which describes single equilibrium). Sometimes the avidity is also called an apparent K D {\displaystyle K_{D}} to emphasize the non-equilibrium nature of the interaction. [ 13 ]
Common oligomerization structures of lectins are shown below. For example, galectins are usually observed as dimers, while intelectins form trimers and pentraxins assemble into pentamers. Larger structures, like hexameric Reg proteins , may assemble into membrane penetrating pores. Collectins may form even more bizarre complexes: bouquets of trimers or even cruciform-like structures (e.g. in SP-D ). [ 14 ]
Given the importance of glycan-protein interactions, there is an ongoing research dedicated to the a) creation of new tools to detect glycan-protein interactions and b) using those tools to decipher the so-called sugar code.
One of the most widely used tools for probing glycan-protein interactions is glycan arrays . A glycan array usually is an NHS- or epoxy -activated glass slides on which various glycans were printed using robotic printing. [ 15 ] [ 16 ] These commercially available arrays may contain up to 600 different glycans, specificity of which has been extensively studied. [ 17 ]
Glycan-protein interactions may be detected by testing proteins of interest (or libraries of those) that bear fluorescent tags . The structure of the glycan-binding protein may be deciphered by several analytical methods based on mass-spectrometry , including MALDI-MS , LC-MS , tandem MS-MS , and/or 2D NMR . [ 18 ]
Computational methods have been applied to search for parameters (e.g. residue propensity, hydrophobicity, planarity) that could distinguish glycan-binding proteins from other surface patches. For example, a model trained on 19 non-homologous carbohydrate binding structures was able to predict carbohydrate-binding domains (CRDs) with an accuracy of 65% for non-enzymatic structures and 87% for enzymatic ones. [ 19 ] Further studies have employed calculations of Van der Waals energies of protein-probe interactions and amino acid propensities to identify CRDs with 98% specificity at 73% sensitivity . [ 20 ] More recent methods can predict CRDs even from protein sequences , by comparing the sequence with those for which structures are already known. [ 21 ]
In contrast with protein studies, where a primary protein structure is unambiguously defined by the sequence of nucleotides (the genetic code ), the glycobiology still cannot explain how a certain "message" is encoded using carbohydrates or how it is "read" and "translated" by other biological entities.
An interdisciplinary effort, combining chemistry, biology, and biochemistry, studies glycan-protein interactions to see how different sequences of carbohydrates initiate different cellular responses. [ 22 ] | https://en.wikipedia.org/wiki/Glycan-protein_interactions |
Glycan arrays , [ 1 ] like that offered by the Consortium for Functional Glycomics (CFG), National Center for Functional Glycomics (NCFG) and Z Biotech, LLC , contain carbohydrate compounds that can be screened with lectins, antibodies or cell receptors to define carbohydrate specificity and identify ligands. Glycan array screening works in much the same way as other microarray that is used for instance to study gene expression DNA microarrays or protein interaction Protein microarrays .
Glycan arrays are composed of various oligosaccharides and/or polysaccharides immobilised on a solid support in a spatially-defined arrangement. [ 2 ] This technology provides the means of studying glycan-protein interactions in a high-throughput environment. These natural or synthetic (see carbohydrate synthesis ) glycans are then incubated with any glycan-binding protein such as lectins , cell surface receptors or possibly a whole organism such as a virus . Binding is quantified using fluorescence-based detection methods. Certain types of glycan microarrays can even be re-used for multiple samples using a method called Microwave Assisted Wet-Erase. [ 3 ]
Glycan arrays have been used to characterize previously unknown biochemical interactions. For example, photo-generated glycan arrays have been used to characterize the immunogenic properties of a tetrasaccharide found on the surface of anthrax spores. [ 4 ] Hence, glycan array technology can be used to study the specificity of host-pathogen interactions . [ 5 ]
Early on, glycan arrays were proven useful in determining the specificity of the Hemagglutinin (influenza) of the Influenza A virus binding to the host and distinguishing across different strains of flu (including avian from mammalian). This was shown with CFG arrays [ 6 ] as well as customised arrays. [ 7 ] Cross-platform benchmarks led to highlight the effect of glycan presentation and spacing on binding. [ 8 ]
Glycan arrays are possibly combined with other techniques such as Surface Plasmon Resonance (SPR) to refine the characterisation of glycan-binding . For example, this combination led to demonstrate the calcium-dependent heparin binding of Annexin A1 that is involved in several biological processes including inflammation , apoptosis and membrane trafficking . [ 9 ] | https://en.wikipedia.org/wiki/Glycan_array |
Glycan nomenclature is the systematic naming of glycans, which are carbohydrate -based polymers made by all living organisms. In general glycans can be represented in ( i ) text formats, these include commonly used CarbBank, IUPAC name, and several other types; and ( ii ) symbol formats, these are consisting of Symbol Nomenclature For Glycans and Oxford Notations.
In the beginning of the nineteenth century, names of sugar molecules were derived from their source. For example, glucose were called grape sugar (Traubenzucker), saccharose were called cane sugar (Rohrzucker). In 1838, the name glucose was coined; subsequently in 1866 Kekulé proposed the name 'dextrose' as glucose is dextrorotatory. It was decided by the scientific community that sugars should be named with the ending '-ose', which then was combined with the French word 'cellule' for cell, resulting in the term cellulose . As the empirical composition of monosaccharides can be expressed as Cn(H 2 O)n, they were termed as ‘carbohydrate’ (French ‘hydrate de carbone’). [ 1 ]
To represent the structural information of glycans more accurate and achieve specific purpose for the community, several unique formats were designed and used in different carbohydrate databases developed through different research groups and organizations.
The CarbBank format is originally from CarbBank, [ 2 ] a database management system for Complex Carbohydrate structure Database (CCSD). The CarbBank is created by researchers at the Complex Carbohydrate Research Center (CCRC) of University of Georgia . An example of an N-glycan of Man-3-Core F is shown below:
In general, this format is human-readable but the vertical bars make it difficult for a computer to parse.
IUPAC is the International Union of Pure and Applied Chemistry, and they propose a nomenclature for representing complex carbohydrates called 2-Carb. [ 3 ] The IUPAC nomenclature provides three forms to represent the glycans.
The above example glycan can be represented as below:
Extended form : α-D-Man p -(1→3)-[α-D-Man p -(1→6)]- β-D-Man p -(1→4)- β-D-Glc p NAc-(1→4)-[ α-L-Fuc p -(1→6)]- β-D-Glc p NAc-(1→NASN-protein
Condensed form : Man(α1-3)[Man(α1-6)]Man(β1-4)GlcNAc(β1-4)[Fuc(α1-6)]GlcNAc(β1-ASN
Short form : Manα3(Manα6)Manβ4GlcNAcβ4(Fucα6)GlcNAcβASN
Note:
Modified Condensed IUPAC : Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1-4(Fucα1-6)GlcNAcβ1-Asn
Linear Notation for Unique description of Carbohydrate Sequences (LINUCS) [ 4 ] is a format used in Glycosciences.de Archived 2021-02-11 at the Wayback Machine . This format is targeted to describe the glycan structure unique . [ 5 ] The glycan example in LINUCS format could be:
Linear Code is a linear notation proposed by GlycoMinds Ltd. and is one of the most compact formats. Here, ( i ) the common monosaccharides are indicated by a maximum two letter code, ( ii ) linkages are indicated by “a” or “b” for anomers, ( iii ) the number are at the end carbon number linkage, and ( iv ) The branches are indicated by parentheses. [ 6 ]
GlycoCT is the format designed and developed under the EuroCarbDB project. This format uses connection table approach to describe the full complexity of carbohydrate sequence data. [ 7 ] It is widely used by the bioinformatics community through the database GlycomeDB . [ 8 ] A GlycoCT format of the example glycan is shown below:
The Web3 Unique Representation of Carbohydrate Structures (WURCS) format is initially developed for GlyTouCan , the international glycan structure repository. As GlyTouCan used the Semantic Web technologies for development, it requires a linear string to represent the glycan. [ 9 ] The example glycan in WURCS format as below:
The KEGG Chemical Function (KCF) is designed and used in Kyoto Encyclopedia of Genes and Genomes ( KEGG ) database. [ 10 ] It also uses a connection table approach. The example glycan in KCF format as below:
Carbohydrate Structure Database (CSDB) includes the Bacterial (BCSDB) [ 11 ] [ 12 ] and Plant and Fungal (PFCSDB) [ 13 ] parts. This database utilizes a connection table for internal storage of structures and the CSDB linear code for input–output.
GLYCAM Condensed format, as well as GLYCAM format, is provided by GLYCAM-Web , which is produced by the research group of Professor Robert J. Woods in the Complex Carbohydrate Research Center at the University of Georgia in Athens GA.
The GLYcan Data Exchange (GLYDE) format, [ 14 ] is an XML-based representation format for glycomics data. It was a part of the Integrated Technology Resources for Biomedical Glycomics, which established by a team from Complex Carbohydrate Research Center of University of Georgia .
GLYDE II, [ 15 ] is the successor of GLYDE to overcome the limitations of GLYDE, uses a connection table approach.
A carbohydrate sequence markup language (CabosML) [ 16 ] is a description of carbohydrate structures using XML.
Many glycobiologists use figures to depict the complex glycan structures. Currently, there are two major ways to represent glycans using symbols: Symbol Nomenclature For Glycans (SNFG) and Oxford Notation.
The Oxford Notation was designed and developed by the researchers from Oxford Glycobiology Institute at University of Oxford in 2009.
To comply with the SNFG notation and respect the Oxford notation some drawing tools [ 17 ] generate hybrid cartoons with the SNFG symbols (monosaccharides) and linkage orientation as set by Oxford.
The scientific community has developed a number of software tools to convert glycans represented in one format to another. Some of these most commonly used tools are listed below: | https://en.wikipedia.org/wiki/Glycan_nomenclature |
Glycation ( non-enzymatic glycosylation ) is the covalent attachment of a sugar to a protein , lipid or nucleic acid molecule. [ 1 ] Typical sugars that participate in glycation are glucose , fructose , and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. [ 2 ] [ 3 ] [ 4 ] Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus . [ 5 ]
In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to a protein or lipid. [ 1 ] Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein.
Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose , fructose , and galactose . It appears that fructose has approximately ten times the glycation activity of glucose, the primary body fuel. [ 8 ] Glycation can occur through Amadori reactions , Schiff base reactions , and Maillard reactions ; which lead to advanced glycation end products (AGEs). [ 1 ]
Red blood cells have a consistent lifespan of 120 days and are accessible for measurement of glycated hemoglobin . Measurement of HbA1c —the predominant form of glycated hemoglobin—enables medium-term blood sugar control to be monitored in diabetes .
Some glycation products are implicated in many age-related chronic diseases, including cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged) and Alzheimer's disease (amyloid proteins are side-products of the reactions progressing to AGEs). [ 9 ] [ 10 ]
Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as crystallins of the lens and cornea ), and DNA can sustain substantial glycation over time. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes. [ 11 ] Glycations also cause weakening of the collagen in the blood vessel walls, [ 12 ] which may lead to micro- or macro-aneurysm; this may cause strokes if in the brain.
The term DNA glycation applies to DNA damage induced by reactive carbonyls (principally methylglyoxal and glyoxal ) that are present in cells as by-products of sugar metabolism. [ 13 ] Glycation of DNA can cause mutation , breaks in DNA and cytotoxicity . [ 13 ] Guanine in DNA is the base most susceptible to glycation. Glycated DNA, as a form of damage, appears to be as frequent as the more well studied oxidative DNA damage. A protein, designated DJ-1 (also known as PARK7 ), is employed in the repair of glycated DNA bases in humans, and homologs of this protein have also been identified in bacteria. [ 13 ] | https://en.wikipedia.org/wiki/Glycation |
Glyceraldehyde 3-phosphate , also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P , GA3P , GADP , GAP , TP , GALP or PGAL , is a metabolite that occurs as an intermediate in several central pathways of all organisms. [ 2 ] [ 3 ] With the chemical formula H(O)CCH(OH)CH 2 OPO 3 2- , this anion is a monophosphate ester of glyceraldehyde .
D-glyceraldehyde 3-phosphate is formed from the following three compounds in reversible reactions:
Compound C05378 at KEGG Pathway Database. Enzyme 4.1.2.13 at KEGG Pathway Database. Compound C00111 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database.
The numbering of the carbon atoms indicates the fate of the carbons according to their position in fructose 6-phosphate.
Compound C00111 at KEGG Pathway Database. Enzyme 5.3.1.1 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database.
Compound C00118 at KEGG Pathway Database. Enzyme 1.2.1.12 at KEGG Pathway Database. Reaction R01063 at KEGG Pathway Database. Compound C00236 at KEGG Pathway Database.
D-glyceraldehyde 3-phosphate is also of some importance since this is how glycerol (as DHAP) enters the glycolytic and gluconeogenic pathways. Furthermore, it is a participant in and a product of the pentose phosphate pathway .
| Click on genes, proteins and metabolites below to link to respective articles. [ § 1 ]
During plant photosynthesis , 2 equivalents of glycerate 3-phosphate (GP; also known as 3-phosphoglycerate) are produced by the first step of the light-independent reactions when ribulose 1,5-bisphosphate (RuBP) and carbon dioxide are catalysed by the rubisco enzyme. The GP is converted to D-glyceraldehyde 3-phosphate (G3P) using the energy in ATP and the reducing power of NADPH as part of the Calvin cycle . This returns ADP , phosphate ions Pi, and NADP + to the light-dependent reactions of photosynthesis for their continued function.
RuBP is regenerated for the Calvin cycle to continue.
G3P is generally considered the prime end-product of photosynthesis and it can be used as an immediate food nutrient, combined and rearranged to form monosaccharide sugars, such as glucose , which can be transported to other cells, or packaged for storage as insoluble polysaccharides such as starch .
6 CO 2 + 6 RuBP (+ energy from 12 ATP and 12 NADPH) →12 G3P (3-carbon)
10 G3P (+ energy from 6 ATP ) → 6 RuBP (i.e. starting material regenerated)
2 G3P → glucose (6-carbon).
Glyceraldehyde 3-phosphate occurs as a byproduct in the biosynthesis pathway of tryptophan , an essential amino acid that cannot be produced by the human body.
Glyceraldehyde 3-phosphate occurs as a reactant in the biosynthesis pathway of thiamine (Vitamin B 1 ), another substance that cannot be produced by the human body.
Glucose
Hexokinase
Glucose 6-phosphate
Glucose-6-phosphate isomerase
Fructose 6-phosphate
Phosphofructokinase-1
Fructose 1,6-bisphosphate
Fructose-bisphosphate aldolase
Dihydroxyacetone phosphate
+
Glyceraldehyde 3-phosphate
Triosephosphate isomerase
2 × Glyceraldehyde 3-phosphate
Glyceraldehyde-3-phosphate dehydrogenase
2 × 1,3-Bisphosphoglycerate
Phosphoglycerate kinase
2 × 3-Phosphoglycerate
Phosphoglycerate mutase
2 × 2-Phosphoglycerate
Phosphopyruvate hydratase ( enolase )
2 × Phosphoenolpyruvate
Pyruvate kinase
2 × Pyruvate | https://en.wikipedia.org/wiki/Glyceraldehyde_3-phosphate |
This page provides supplementary chemical data on glycerol .
The handling of this chemical may incur notable safety precautions. It is highly recommended that you seek the Material Safety Datasheet ( MSDS ) for this chemical from a reliable source and follow its directions.
Table data obtained from CRC Handbook of Chemistry and Physics , 44th ed.
log e of Glycerol vapor pressure. Uses formula: log e P k P a = {\displaystyle \scriptstyle \log _{e}P_{kPa}=} A × l n ( T ) + B / T + C + D × T 2 {\displaystyle \scriptstyle A\times ln(T)+B/T+C+D\times T^{2}} with coefficients A=-2.125867E+01, B=-1.672626E+04, C=1.655099E+02, and D=1.100480E-05 obtained from CHERIC [ 5 ]
Table data obtained from Lange's Handbook of Chemistry , 10th ed. Specific gravity is at 15 °C, referenced to water at 15 °C.
See details on: Freezing Points of Glycerine-Water Solutions Dow Chemical [ 6 ] or Freezing Points of Glycerol and Its Aqueous Solutions. [ 7 ] | https://en.wikipedia.org/wiki/Glycerol_(data_page) |
Glycerol 2-phosphate is the conjugate base of phosphoric ester of glycerol . It is commonly known as β-glycerophosphate or BGP . Unlike glycerol 1-phosphate and glycerol 3-phosphate , this isomer is not chiral. It is also less common.
β-Glycerophosphate is an inhibitor of the enzyme serine/threonine phosphatase . It is often used in combination with other phosphatase/protease inhibitors for broad spectrum inhibition. [ 1 ] [ 2 ]
Although previously presumed to be non-transportable and reliant on extracellular phosphatases such as alkaline phosphatase (PhoA) for utilization, recent research indicates that Escherichia coli can use β-Glycerophosphate as a sole phosphorus source in the absence of PhoA, relying on the Ugp transporter system encoded by the ugpBAECQ operon. [ 3 ]
β-Glycerophosphate is also used to drive osteogenic differentiation of bone marrow stem cells in vitro . [ 4 ]
β-Glycerophosphate is used to buffer M17 media for Lactococcus culture in recombinant protein expression . [ 5 ]
Glycerol 2-phosphate (G2P) can be formed through abiotic phosphorylation under prebiotic conditions, as demonstrated in laboratory simulations of early Earth environments. [ 6 ] In the presence of urea and heat, glycerol and phosphate undergo regioselective phosphorylation, favoring the 2-position to yield G2P. [ 6 ] This process suggests a plausible prebiotic pathway for the synthesis of key metabolic intermediates like G2P, which may have contributed to the origin of biological phospholipid synthesis prior to enzymatic catalysis. [ 6 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glycerol_2-phosphate |
The chemical redox reaction between potassium permanganate and glycerol [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] is often used to demonstrate the powerful oxidizing property of potassium permanganate , especially in the presence of organic compounds such as glycerol. The exothermic (heat producing) reaction between potassium permanganate (KMnO 4 ), a strong oxidizing agent , and glycerol (C 3 H 5 (OH) 3 ), a readily oxidised organic substance , is an example of an experiment sometimes referred to as a "chemical volcano". [ 7 ] [ 8 ]
Potassium permanganate (KMnO 4 ) is a dark violet colored powder. Its reaction with glycerol (commonly known as glycerin or glycerine) (C 3 H 5 (OH) 3 ) is highly exothermic , resulting rapidly in a flame, along with the formation of carbon dioxide and water vapour :
14 KMnO 4 (s) + 4 C 3 H 5 (OH) 3 (l) → 7 K 2 CO 3 (s) + 7 Mn 2 O 3 (s) + 5 CO 2 (g) + 16 H 2 O(g). [ 1 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]
Crystalline potassium permanganate (KMnO 4 ) is placed in an evaporating dish . A depression is made at the center of the permanganate powder and glycerol liquid is added to it. The white smoke-like vapor produced by the reaction is a mixture of carbon dioxide gas and water vapor. Since the reaction is highly exothermic, initial sparking occurs, followed by a lilac - or pink -colored flame. [ 9 ] When energy or heat is added to electrons , their energy level increases to an excited state . This state is short-lived, and once the electrons release the energy, they return to their normal energy levels. [ 2 ] During this process the energy is visibly observed as light. [ 10 ] When the reaction is complete, it leaves behind a grayish solid with green regions. [ 1 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] | https://en.wikipedia.org/wiki/Glycerol_and_potassium_permanganate |
Glycerol dialkyl glycerol tetraether lipids (GDGTs) are a class of membrane lipids synthesized by archaea and some bacteria , making them useful biomarkers for these organisms in the geological record. Their presence, structure, and relative abundances in natural materials can be useful as proxies for temperature, terrestrial organic matter input, and soil pH for past periods in Earth history. [ 1 ] Some structural forms of GDGT form the basis for the TEX86 paleothermometer . [ 1 ] Isoprenoid GDGTs, now known to be synthesized by many archaeal classes, were first discovered in extremophilic archaea cultures. [ 2 ] Branched GDGTs, likely synthesized by acidobacteriota , [ 3 ] were first discovered in a natural Dutch peat sample in 2000. [ 4 ]
The phospholipid built from a two-headed tetraether lipid is often called a bolalipid . In a membrane bilayer, a bolalipid can appear in a straight "O-shape" conformation where it spans both sides, or appear in a U-shaped conformation where its two phosphate heads are on the same side. [ 5 ] [ 6 ]
The chemical nature of GDGTs is succinctly described by its name: they consist of two glycerol molecules connected via two alkyl chains, being held together at four ether linkages. In the living microbe, they are attached to two phosphate head groups that allow them to work as membrane phospholipids . [ 1 ] Compared to the typical lipid bilayer in eukaryotes and most bacteria, GDGT-diphosphates differ by having two headgroups, which allow one molecule to do the job of two typical phospholipids (allowing monolayers in water) and resist heat better. They are also connected by ether, instead of ester, bonds. [ 7 ]
The two primary structural classes of GDGTs are isoprenoid (isoGDGT) and branched (brGDGT), which refer to differences in the carbon skeleton structures. [ 1 ]
Isoprenoid GDGTs originate as archaeal membrane lipids , whose fatty acids are converted to glycerol via esterification ( ether lipid ). [ 1 ] They were first recognized as being associated with extremophilic archaea, [ 2 ] but research in recent decades has discovered the compounds in a wide range of mesophilic environments as well, including soils, lake sediment, and marine deposits. [ 1 ] Archaeal phylogenetic classes Nitrososphaerota (formerly Thaumarchaeota), Thermoproteota (formerly Crenarchaeota), " Euryarchaeota ", and " Korarchaeota " produce GDGTs. [ 1 ]
Branched GDGTs are most commonly detected in peats and soils and are most associated with terrestrial settings. To date, no direct evidence for an unequivocal source organism has been reported, but the structural similarity of acidobacterial lipid to brGDGT alkyl chains strongly suggests that acidobacteriota synthesize brGDGT. [ 3 ] The stereochemistry strongly hints at a non-archaeal origin. [ 8 ]
GDGT-0 has zero cyclopentane moieties and is the most ubiquitous isoGDGT synthesized by archaea. Halophilic archaea are the only group of archaea not known to produce GDGT-0. [ 1 ] Carbon isotope analyses and association with sites of anaerobic methane oxidation suggest that GDGT-0 is produced via methanotrophs . [ 1 ] In microbiology literature not dealing with the geological record, GDGT-0 is sometimes referred to as caldarchaeol . [ 1 ]
GDGT-1, GDGT-2, and GDGT-3 have one, two, and three cyclopentane rings respectively within their isoprenoid biphytane carbon structures, respectively. Nitrososphaerota are the largest producers of these groups in marine and lacustrine environments. [ 1 ] Methanogens are not thought to be large synthesizers of these molecules, with the exception of Methanopyrus kandleri , which does produce them. [ 1 ] These classes are lower in abundance than GDGT-0 and GDGRT-4. They are used in the TEX86 paleothermometer . [ 1 ]
GDGT-4 refers to the version with four cyclopentane rings. It is quite abundant (although not easy to differentiate from crenarchaeol on GC/MS, see below). Nitrososphaerota also makes GDGT-4. [ 9 ]
Crenarchaeol is mainly attributed to ammonium-oxidizing Nitrososphaerota and has four cyclopentane rings plus one cyclohexane ring, which distinguishes it from GDGT-4 and is unique to the Nitrososphaerota phylum. [ 1 ] The evolution of the cyclohexane ring was likely to adjust the density of the membrane packing to more optimally function at the cooler ocean temperatures to which Nitrososphaerota adapted. [ 10 ] Due to their structural similarities, crenarchaeol and GDGT-4 have similar GC/MS elution times. [ 1 ] They are similar in prevalence to GDGT-0 and therefore are not included in the TEX 86 paleothermometer because their abundance overwhelms the less abundant GDGT groups. [ 11 ]
A crenarchaeol regioisomer , however, is a part of the TEX 86 paleothermometer . This isomer likely differs by having a cis configuration on the cyclopentane ring neighboring the additional cyclohexane ring. It is presumed to be also made by Nitrososphaerota. [ 11 ]
GDGTs -5 through -8 are nearly exclusive to extreme high-temperature environments such as hot springs. The larger number of cyclopentane moieties facilitates a more densely packed membrane lipid structure, which better inhibits trans-membrane passage of protons and ions. Doing so increases the molecules' thermal stability, which is necessary to survive at extreme temperatures. [ 12 ] [ 10 ]
Two proteins responsible for making these GDGTs were identified in Sulfolobus acidocaldarius , a thermoacidophile. grsA is responsible for producing the four cyclopentane rings at the C7 position (also seen in less ring-rich GDGTs), while grsB cyclizes at the unique C3 position. Homologs of the two genes are found throughout Nitrososphaerota . [ 13 ]
The building blocks of brGDGT, specifically the long alkyl groups ( iso-diabolic acid ), are detected in acidobacteria subdivisions 1, 3, 4, and 6. [ 3 ] [ 14 ] [ 15 ] Small amounts of brGDGT-I was detected in Acidobacteriaceae strain A2-4c by full mass spectrum and tentatively in Acidobacteriaceae strain 307 by single-ion monitoring MS; [ 3 ] none has been detected in the 44 other strains tested as of 2018. [ 15 ] More complex brGDGTs known from nature have not yet been detected in any cell culture. [ 14 ]
Because the number of cyclopentane moieties in a GDGT compound is related to the temperature of the growth environment, with increasing numbers of cyclopentane rings resulting in increased thermal stability and allowing for survival at higher temperatures, GDGT distribution and abundance can be employed as paleoclimate proxies . [ 1 ] TEX86 is one such paleothermometer which relates distribution and relative abundance of GDGT-1, GDGT-2, GDGT-3, and crenarchaeol isomer to past sea surface temperature (SST) (see TEX86 ). [ 1 ] GDGT-0, GDGT-4, and crenarchaeol are excluded from consideration for this proxy due to their very high abundances relative to isoGDGTs 1–3. [ 1 ] The relationship between isoGDGT distribution and temperature is not linear, and some studies have demonstrated its distinctive bias towards unrealistically cold temperatures in the lower latitudes. [ 17 ] Current research suggests TEX86 works best in the temperature range 15-34 degrees Celsius. [ 1 ] Seasonal variability in archaeal productivity and depth in the water column at which the archaea grow should be considered prior to employing this proxy. [ 1 ]
The branched:isoprenoid tetraether (BIT) index relates the relative abundances of brGDGTs in a natural sample to the relative abundance of soil organic matter in that sample. It is calculated by ratioing a sum of bacterially-produced brGDGT abundances over a sum of archaeal isoGDGT abundances and is based on the fundamental idea that brGDGTs are produced most commonly in terrestrial environments (most ubiquitous in soils and peats) while archaeal isoGDGTs (particularly crenarchaeol) are produced in marine environments. [ 1 ] While caveats and analytical uncertainties remain an issue, the BIT index is a potentially useful proxy for assessing the amount of fluvially transported soil organic matter compared to marine organic matter. [ 1 ]
The methylation of branched tetraethers (MBT) and cyclization of branched tetraethers (CBT) indices relate abundances and distributions of bacterially-produced brGDGTs to relative changes in soil pH and mean annual air temperature. [ 1 ] Further research is needed to assess seasonal bias, appropriate calibration protocols, and whether the brGDGT distributions record air or soil temperature. [ 1 ]
GDGTs are identified via organic geochemical analysis as the polar head groups of the membrane lipids. High-precision liquid chromatography mass spectrometry (HPLC-MS) is the primary means by which GDGTs are analyzed due to this method's tolerance for high temperatures. [ 1 ] | https://en.wikipedia.org/wiki/Glycerol_dialkyl_glycerol_tetraether |
The glycerol-3-phosphate shuttle is a mechanism used in skeletal muscle and the brain [ 1 ] that regenerates NAD + from NADH , a by-product of glycolysis . NADH is a reducing equivalent that stores electrons generated in the cytoplasm during glycolysis. NADH must be transported into the mitochondria to enter the oxidative phosphorylation pathway. However, the inner mitochondrial membrane is impermeable to NADH and only contains a transport system for NAD + . Depending on the type of tissue either the glycerol-3-phosphate shuttle pathway or the malate–aspartate shuttle pathway is used to transport electrons from cytoplasmic NADH into the mitochondria. [ 2 ]
The shuttle consists of two proteins acting in sequence. Cytoplasmic glycerol-3-phosphate dehydrogenase (cGPD) transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating the NAD + needed to generate energy via glycolysis. [ 3 ] Mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) then catalyzes the oxidation of G3P by FAD , regenerating DHAP in the cytosol and forming FADH 2 in the mitochondrial matrix. [ 4 ] In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is secondary to the malate–aspartate shuttle.
The glycerol phosphate shuttle was first characterized as a major route of mitochondrial hydride transport in the flight muscles of blow flies . [ 5 ] [ 6 ] It was initially believed that the system would be inactive in mammals due to the predominance of lactate dehydrogenase activity over glycerol-3-phosphate dehydrogenase 1 (GPD1) [ 5 ] [ 7 ] until high GPD1 and GPD2 activity were demonstrated in mammalian brown adipose tissue and pancreatic ß-islets . [ 8 ] [ 9 ] [ 10 ] [ 11 ]
In this shuttle, the enzyme called cytoplasmic glycerol-3-phosphate dehydrogenase 1 (GPD1 or cGPD) converts dihydroxyacetone phosphate (2) to glycerol 3-phosphate (1) by oxidizing one molecule of NADH to NAD + as in the following reaction:
Glycerol-3-phosphate is converted back to dihydroxyacetone phosphate by an inner membrane-bound mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2 or mGPD), this time reducing one molecule of enzyme-bound flavin adenine dinucleotide (FAD) to FADH 2 . FADH 2 then reduces coenzyme Q (ubiquinone to ubiquinol) whose electrons enter into oxidative phosphorylation . [ 12 ] This reaction is irreversible. [ 13 ] These electrons bypass Complex I of the electron transport chain , making the glycerol-3-phosphate shuttle less energetically efficient compared to oxidation of NADH by Complex I. [ 14 ] | https://en.wikipedia.org/wiki/Glycerol_phosphate_shuttle |
In organic chemistry glycerolysis refers to any process in which chemical bonds are broken via a reaction with glycerol . The term refers almost exclusively to the transesterification reaction of glycerol with triglycerides (fats/oils) to form mixtures of monoglycerides and diglycerides . These find a variety of uses; as food emulsifiers (e.g. E471 ), 'low fat' cooking oils (e.g. diacylglycerol oil ) and surfactants (such as monolaurin ).
The transesterification process gives a complex mixture of products, however not all of these are of equivalent use. [ 1 ] This has led to the development of optimized processes able to produce better defined products; in particular by using enzymes , [ 2 ] reactions in supercritical carbon dioxide and flow chemistry . [ 3 ] The production of diglycerides (often called diacylglycerols or DAGs) have been investigated extensively due to their use in foods, with total annual sales of approximately US$200 million in Japan since its introduction in the late 1990s until 2009. [ 2 ] [ 4 ] | https://en.wikipedia.org/wiki/Glycerolysis |
Glyceroneogenesis is a metabolic pathway which synthesizes glycerol 3-phosphate (used to form triglycerides ) from precursors other than glucose . [ 1 ] Usually, glycerol 3-phosphate is generated from glucose by glycolysis , in the liquid of the cell's cytoplasm (the cytosol ). Glyceroneogenesis is used when the concentrations of glucose in the cytosol are low, and typically uses pyruvate as the precursor, but can also use alanine , glutamine , or any substances from the TCA cycle . The main regulator enzyme for this pathway is an enzyme called phosphoenolpyruvate carboxykinase (PEPC-K), which catalyzes the decarboxylation of oxaloacetate to phosphoenolpyruvate . [ 1 ] Glyceroneogenesis is observed mainly in adipose tissue , and in the liver . A significant biochemical pathway regulates cytosolic lipid levels. Intense suppression of glyceroneogenesis may lead to metabolic disorders such as type 2 diabetes . [ 2 ]
Triglycerides are built from three fatty acids , esterified onto each of three hydroxy groups of glycerol , which is derived from glycerol 3-phosphate. In mammals, glycerol 3-phosphate is usually synthesized through glycolysis, a metabolic pathway that degrades glucose into fructose 1,6-bisphosphate and then into two molecules of dihydroxyacetone phosphate , which beget glycerol 3-phosphate and glyceraldehyde 3-phosphate . [ 1 ] When an organism is deficient in glucose, from (for example) fasting or a low carbohydrate intake, glycerol 3-phosphate is generated by glyceroneogenesis instead. As well as synthesizing lipids for use in other metabolic processes, glyceroneogenesis regulates lipid levels in the cytosol. [ 1 ]
The main precursors of glyceroneogenesis are pyruvate , lactate , glutamine , and alanine . Glyceroneogenesis is also known as the branched pathway of gluconeogenesis because its first few steps are the same.
When pyruvate or lactate is used as the precursor for glycerol 3-phosphate, glyceroneogenesis follows the same pathway as gluconeogenesis until it generates dihydroxyacetone phosphate. Lactate catalyzed by lactate dehydrogenase will form pyruvate at the expense of NAD+ . By using one ATP and bicarbonate , pyruvate will be converted to oxaloacetate , catalysed by pyruvate carboxylase . The PEPC-K enzyme will catalyze oxaloacetate to generate phosphoenolpyruvate . This phosphorylation and decarboxylation of oxaloacetate is a significant step in glyceroneogenesis, since it regulates the entire pathway. After the production of phosphoenolpyruvate, gluconeogenesis will continue until dihydroxyacetone phosphate is generated, which produces 2-phosphoglycerate , 3-phosphoglycerate , 1,3-bisphosphoglycerate and glyceraldehyde 3-phosphate as intermediates. When dihydroxyacetone phosphate is produced, glyceroneogenesis will branch off from gluconeogenesis. [ 1 ] With the expense of NADH , dihydroxyacetone phosphate will convert to glycerol 3-phosphate, which is the final product of glyceroneogenesis. In addition, triglyceride can be generated by re-esterifying 3 fatty acid chains on glycerol 3-phosphate. Instead of producing fructose 1,6- bisphosphate as gluconeogenesis does, glyceroneogenesis converts dihydroxyacetone phosphate to glycerol 3-phosphate.
Alanine can also be used as a precursor of glyceroneogenesis because alanine can be degraded to pyruvate. Alanine will degrade to pyruvate by transferring its amino group to 2-oxoglutarate with an enzyme called alanine aminotransferase . Alanine aminotransferase cleaves off the amino group from alanine and binds it to 2-oxoglutarate, generating pyruvate from alanine, and glutamate from 2-oxoglutarate. Pyruvate generated from alanine will enter glyceroneogenesis and generate glycerol 3-phosphate.
Glutamate can also enter glyceroneogenesis. Since the key reaction of glyceroneogenesis is the decarboxylation and phosphorylation of oxaloacetate to phosphoenolpyruvate, in theory any biochemical pathway which generates oxaloacetate is related to glyceroneogenesis. For example, glutamate can generate oxaloacetate in 2 steps. Firstly, glutamate can be converted to 2-oxoglutarate with the expense of NAD+ and H 2 O with the help of glutamate dehydrogenase . Secondly, 2-oxoglutarate can enter the tricarboxylic acid cycle to generate oxaloacetate. Therefore, theoretically any metabolites in the TCA cycle or any metabolites generating the metabolites of the TCA cycle can be used as a precursor of glyceroneogenesis, but glutamate is the only precursor confirmed.
Glyceroneogenesis can be regulated at two reaction pathways. First, it can be held at the decarboxylation of oxaloacetate to phosphoenolpyruvate. Secondly, the TCA cycle can affect glyceroneogenesis when the glutamate or substrates in the TCA cycle are being used as a precursor.
Decarboxylation of oxaloacetate to phosphoenolpyruvate is catalyzed by PEPC-K, the essential enzyme which regulates glyceroneogenesis. [ 1 ] Increases in PEPC-K levels or overexpression of the gene that codes for PEPC-K will increase glyceroneogenesis. Also, oxaloacetate can be decarboxylated to phosphoenolpyruvate when more PEPC-K can catalyze the reaction.
Gene expression of PEPC-K can be suppressed by norepinephrine , glucocorticoids , and insulin . [ 3 ] Norepinephrine is a neurotransmitter which decreases the activity of PEPC-K when the cell is in a cold environment. Glucocorticoids are steroid hormones involved in the reciprocal regulation of glyceroneogenesis in the liver and adipose tissues. Through a poorly-understood mechanism, they induce transcription of PEPC-K in the liver while decreasing transcription in adipose tissues. Insulin is a peptide hormone that causes cells to take in glucose. Through glyceroneogenesis, insulin down-regulates the expression of PEPC-K in both liver and adipose tissues.
When metabolites from the TCA cycle or glutamate are used as a precursor for glyceroneogenesis, the regulator in the TCA cycle can also cause fluctuations in the levels of products formed by glyceroneogenesis. Regulation of the TCA cycle is mainly determined by product inhibition and substrate availability. The TCA cycle will slow down when the environment contains excess product, or deficiency of the substrate such as ADP and NAD+ .
Since glyceroneogenesis is related to lipid regulation, it can be found in adipose tissue and the liver . In adipose tissue, glyceroneogenesis restrains the release of free fatty acids (FFA) by re-esterifying them. In the liver, triglycerides are synthesized for lipid distribution.
White adipose tissue, also known as white fat, is one two types of adipose tissue in mammals. White adipose tissue stores energy in the form of triglycerides, which can be broken down to free fatty acids on demand. Its normal function is to store free fatty acids as triglycerides within the tissue. When glucose is deficient, in situations like fasting , white adipose tissue generates glycerol 3-phosphate. [ 3 ]
Brown adipose tissue stores free fatty acids rather than triglycerides, and is especially abundant in newborn and hibernating mammals. Brown adipose tissue is involved in thermogenesis , and has a considerably higher glyceroneogenesis activity. [ 3 ] Brown adipose tissue contains more glyceroneogenesis-related enzymes, in particular PEPC-K and glycerol kinase. PEPC-K is around 10 times more active than in white adipose tissue, and is the key regulatory enzyme that controls the activity of the pathway. [ 3 ] Glycerol kinase phosphorylates glycerol to generate glycerol 3-phosphate, which is used to build triglycerides. An increase in the activity of glycerol kinase will increase the production of glycerol 3-phosphate.
Glyceroneogenesis in brown adipose tissue contributes to thermogenesis, a process that generates heat in warm-blooded animals by delivering free fatty acids to the mitochondria . [ 3 ] In normal conditions, thermogenesis is down-regulated by the low concentration of free fatty acids in the cytosol, because glyceroneogenesis re-esterifies fatty acids to triglycerides. When exposed to cold, a neurotransmitter hormone called norepinephrine suppresses the activity of PEPC-K and thus the glyceroneogenesis re-esterification, increasing the availability of free fatty acids within the cell. [ 3 ] Excess free fatty acids in the cytosol will consequently be delivered to the mitochondria for thermogenesis. [ 4 ]
Although glyceroneogenesis was first found in adipose tissues, it was not recognized in the liver until 1998. [ citation needed ] This finding was unexpected because triglyceride synthesis in the liver was thought not to occur due to the amount of gluconeogenesis taking place [ clarification needed ] , and because the liver was believed to have sufficient glycerol 3-phosphate collected from the bloodstream . Several experiments using stable isotopes to track the glycerol in the liver and bloodstream, showed that 65% of the glycerol backbone of triglycerides in the bloodstream is synthesized in the liver. [ 3 ] It was subsequently found that the liver synthesizes more than half of the glycerol mammals need to regulate lipids.
Glyceroneogenesis in the liver and adipose tissues regulate lipid metabolism in opposite ways. Lipids as triglycerides are released from the liver, while glyceroneogenesis restrains the fatty acid release from adipose tissues by re-esterifying them. [ 3 ] When the lipid concentration in the blood is relatively high, glyceroneogenesis in the liver will be down-regulated to stop the synthesis of triglycerides, but glyceroneogenesis in adipose tissues will be induced in order to restrain the release of free fatty acid to the bloodstream. Conversely, glyceroneogenesis is induced in the liver and suppressed in adipose tissues when the blood lipid level is low. Although the reciprocal regulation of glyceroneogenesis is not well understood, a hormone called glucocorticoid is involved in the regulation. [ 4 ] Glucocorticoids induce gene transcription of PEPC-K in liver but repress the transcription in adipose tissues.
Failure in the regulation of glyceroneogenesis may lead to type 2 diabetes , a metabolic disorder that results in high levels of blood glucose and blood lipid. [ 5 ] Type 2 diabetes, in addition to a decreased sensitivity to insulin , is associated with the overproduction of triglycerides in the liver, due to excessively active glyceroneogenesis and excess release of fatty acids from adipose tissues. Glyceroneogenesis can be regulated by controlling the gene expression of PEPC-K.
Overexpressing PEPC-K in the liver will overproduce triglycerides and elevate the lipid level in the bloodstream, increasing the risk of fatty liver disease (hepatic steatosis). Conversely, in adipose tissue, down-regulated glyceroneogenesis may decrease de novo lipogenesis, increasing the export of free fatty acids to the bloodstream, leading to lipodystrophy . Both of these conditions are highly associated with type 2 diabetes.
Regulation of glyceroneogenesis is a therapeutic target of type 2 diabetes treatment, specifically inhibiting it in the liver and increasing it in adipose tissues. Insulin down-regulates glyceroneogenesis in the liver, but it also suppresses it in adipose tissue. To restrict the release of free fatty acids from adipose tissues, glyceroneogenesis must be increased so they are re-esterified. Thiazolidinedione is a substance that only affects glyceroneogenesis in adipose tissue by increasing transcription of PEPC-K to up-regulate glyceroneogenesis. [ 5 ] | https://en.wikipedia.org/wiki/Glyceroneogenesis |
Glycinamide is an organic compound with the molecular formula H 2 NCH 2 C(O)NH 2 . It is the amide derivative of the amino acid glycine . It is a water-soluble, white solid. Amino acid amides, such as glycinamide are prepared by treating the amino acid ester with ammonia. [ 1 ]
It is a ligand for transition metals, related to amino acid complexes . As a neutral ligand, it binds through the amine. In some complexes, it binds through the amine and the carbonyl oxygen, forming a five-membered chelate ring. [ 2 ]
The hydrochloride salt of glycinamide, glycinamide hydrochloride, is one of Good's buffers with a pH in the physiological range. Glycinamide hydrochloride has a pKa near the physiological pH (8.20 at 20°C), making it useful in cell culture work. Its ΔpKa/°C is -0.029 and it has a solubility in water at 0 °C of 6.4 M.
Glycinamide is a reagent used in the synthesis of glycineamide ribonucleotide (an intermediate in de novo purine biosynthesis ). [ 3 ]
This article about an amine is a stub . You can help Wikipedia by expanding it .
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glycinamide |
The glycine cleavage system ( GCS ) is also known as the glycine decarboxylase complex or GDC . The system is a series of enzymes that are triggered in response to high concentrations of the amino acid glycine . [ 1 ] The same set of enzymes is sometimes referred to as glycine synthase when it runs in the reverse direction to form glycine. [ 2 ] The glycine cleavage system is composed of four proteins: the T-protein, P-protein, L-protein, and H-protein. They do not form a stable complex, [ 3 ] so it is more appropriate to call it a "system" instead of a "complex". The H-protein is responsible for interacting with the three other proteins and acts as a shuttle for some of the intermediate products in glycine decarboxylation. [ 2 ] In both animals and plants, the glycine cleavage system is loosely attached to the inner membrane of the mitochondria. Mutations in this enzymatic system are linked with glycine encephalopathy . [ 2 ]
In plants, animals and bacteria the glycine cleavage system catalyzes the following reversible reaction:
In the enzymatic reaction, H-protein activates the P-protein, which catalyzes the decarboxylation of glycine and attaches the intermediate molecule to the H-protein to be shuttled to the T-protein. [ 4 ] [ 5 ] The H-protein forms a complex with the T-protein that uses tetrahydrofolate and yields ammonia and 5,10-methylenetetrahydrofolate . After interaction with the T-protein, the H-protein is left with two fully reduced thiol groups in the lipoate group. [ 6 ] The glycine protein system is regenerated when the H-protein is oxidized to regenerate the disulfide bond in the active site by interaction with the L-protein, which reduces NAD + to NADH and H + .
When coupled to serine hydroxymethyltransferase , the glycine cleavage system overall reaction becomes:
In humans and most vertebrates, the glycine cleavage system is part of the most prominent glycine and serine catabolism pathway. This is due in large part to the formation 5,10-methylenetetrahydrofolate , which is one of the few C 1 donors in biosynthesis. [ 2 ] In this case the methyl group derived from the catabolism of glycine can be transferred to other key molecules such as purines and methionine .
This reaction, and by extension the glycine cleavage system, is required for photorespiration in C 3 plants. The glycine cleavage system takes glycine, which is created from an unwanted byproduct of the Calvin cycle , and converts it to serine which can reenter the cycle. The ammonia generated by the glycine cleavage system, is assimilated by the Glutamine synthetase - Glutamine oxoglutarate aminotransferase cycle but costs the cell one ATP and one NADPH . The upside is that one CO 2 is produced for every two O 2 that are mistakenly taken up by the cell, generating some value in an otherwise energy depleting cycle. Together the proteins involved in these reactions comprise about half the proteins in mitochondria from spinach and pea leaves . [ 3 ] The glycine cleavage system is constantly present in the leaves of plants, but in small amounts until they are exposed to light. During peak photosynthesis, the concentration of the glycine cleavage system increases ten-fold. [ 7 ]
In the anaerobic bacteria, Clostridium acidiurici , the glycine cleavage system runs mostly in the direction of glycine synthesis. While glycine synthesis through the cleavage system is possible due to the reversibility of the overall reaction, it is not readily seen in animals. [ 8 ] [ 9 ]
Glycine encephalopathy , also known as non-ketotic hyperglycinemia (NKH), is a primary disorder of the glycine cleavage system, resulting from lowered function of the glycine cleavage system causing increased levels of glycine in body fluids. The disease was first clinically linked to the glycine cleavage system in 1969. [ 10 ] Early studies showed high levels of glycine in blood, urine and cerebrospinal fluid. Initial research using carbon labeling showed decreased levels of CO 2 and serine production in the liver, pointing directly to deficiencies glycine cleavage reaction. [ 11 ] Further research has shown that deletions and mutations in the 5' region of the P-protein are the major genetic causes of nonketotic hyperglycinemia. . [ 12 ] In more rare cases, a missense mutation in the genetic code of the T-protein, causing the histidine in position 42 to be mutated to arginine , was also found to result in nonketotic hypergycinemia. This specific mutation directly affected the active site of the T-protein, causing lowered efficiency of the glycine cleavage system. [ 13 ]
(See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase) | https://en.wikipedia.org/wiki/Glycine_cleavage_system |
A glycinergic agent (or drug ) is a chemical which functions to directly modulate the glycine system in the body or brain. Examples include glycine receptor agonists , glycine receptor antagonists , and glycine reuptake inhibitors .
This drug article relating to the nervous system is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glycinergic |
Glycoazodyes (or GADs) are a family of "naturalised" synthetic dyes , so called because they are the conjugation of common commercial azo dyes with sugar through a "linker". [ 1 ] This principle is summarised in the scheme below.
The first-generation of Glycoazodyes was first reported in 2007. These Glycoazodyes use a diester linker, specifically a succinyl bridge. An ester group bonds the sugar to an n- alkane spacer, and the spacer bonds to the dye through another ester group. [ 1 ]
First-generation Glycoazodyes are synthesized using glucose , galactose or lactose as the sugar group. The point of esterification is controlled by selectively protecting alcohol groups on the sugar, or by choosing an azo dye with a different alcohol group position. The dye or the sugar group can be succinylated by reacting a free alcohol group with succinic anhydride . The resulting hemisuccinate then reacts with a free alcohol group on the dye or the sugar. The condensation product is then deprotected. [ 1 ]
The second-generation of Glycoazodyes was first reported in 2008. These Glycoazodyes use an etherel linker. An ether group bonds the sugar and the dye to an n- alkane spacer, and the spacer bonds to the dye through another ether group. Like first-generation Glycoazodyes, second-generation Glycoazodyes use glucose, galactose or lactose as the sugar group. [ 2 ]
Like first-generation Glycoazodyes, second-generation Glycoazodyes are synthesized using a glucose , galactose , or lactose sugar group. The point of the ether bond is controlled by selectively protecting alcohol groups on the sugar, or by choosing an azo dye with a different alcohol group position. An unprotected alcohol group of either the sugar or the dye is reacted with an n-carbon, terminal dibromoalkane in a solution of potassium hydroxide and 18-crown-6 ether, using non- anhydrous tetrahydrofuran as the solvent . The potassium hydroxide produces an alkoxide ion from the alcohol while the 18-crown-6 ether acts as a phase-transfer agent . The reaction proceeds through a classic SN-2 nucleophilic substitution . A terminal Bromo group is eliminated, and a bond is formed between the oxygen of the alcohol and the carbon of the alkane. An ether is produced between the n-carbon linker and the sugar or the dye. At this stage, the terminal Bromo group that remains may react under the same conditions with the free alcohol of a corresponding sugar or dye. The condensation product is then deprotected. [ 2 ]
The third-generation of Glycoazodyes was first reported in 2015. These Glycoazodyes use an amido-ester linker. An amide group bonds the sugar to an n- alkane spacer, and the spacer is bonded to the dye through an ester group. [ 3 ]
Third-generation Glycoazodyes are synthesized using amino sugars such as 6-amino-6-deoxy-D-galactose or 6' amino-6'-deoxylactose. The point of the amide bond is controlled by protecting the alcohol groups on the sugar and allowing the free amine to react. The point of the ester group is controlled by choosing a azo dye with a different alcohol group position. Either the dye or the sugar is reacted with succinic anhydride . This forms an amide group with the sugar or an ester group with the dye. The free carboxylic acid may then react with the alcohol group or amine group on the corresponding dye or sugar. The condensation product is then deprotected. [ 3 ]
A variety of fabrics such as wool , silk , nylon , polyester , polyacrylic , polyacetate , and polyurethane may be dyed with Glycoazodyes under moderate temperatures and pressures in aqueous solutions. [ 1 ] [ 2 ] First-generation Glycoazodyes dye cotton poorly. [ 1 ] However, second-generation Glycoazodyes dye cotton effectively. [ 2 ] Wool dyed with Glycoazodyes shows good fastness when exposed to the ISO 105-C06 washing and ISO 105 X12 rubbing tests. [ 4 ]
Glycoazodyes vary in their water solubility. They may be soluble in cold to warm water and may dissolve after stirring or upon addition. [ 4 ]
Minor variations in absorption spectra occur when Glycoazodye solutions are prepared, using water, acetone, or methanol solvents. [ 1 ] Converting a parent azo dye to a Glycoazodye may produce a small hypsochromic shift in the absorption spectra.
Several properties may make Glycoazodyes an environmentally friendly alternative to traditional synthetic dyes . The increased hydrophilicity of Glycoazodyes allows for the elimination of surfactants , mordants , and salts , during the dyeing process and permits the aqueous dying of a variety of textiles at moderate temperatures and pressures. The unique structure may also allow for the treatment of textile effluent through biological means. Fusarium oxysporum efficiently decolourizes the first-generation Glycoazodye 4-{N,N-Bis[2-(D-galactopyranos-6-yloxy)ethyl]-amino}azobenzene. Various other Ascomycota fungi show a similar potential to decolourise Glycoazodyes, but to a lesser extent. Detoxification has been measured, using the Daphnia magna acute toxicity test, showing a 92% dye detoxification after 6 days. This detoxification method produces low concentrations of nitrobenzene , aniline , and nitrosobenzene . [ 5 ]
^ | https://en.wikipedia.org/wiki/Glycoazodyes |
Defined in the narrowest sense, glycobiology is the study of the structure, biosynthesis, and biology of saccharides ( sugar chains or glycans ) that are widely distributed in nature. [ 1 ] [ 2 ] Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology are researched in various medical, biochemical and biotechnological fields.
According to Oxford English Dictionary the specific term glycobiology was coined in 1988 by Prof. Raymond Dwek to recognize the coming together of the traditional disciplines of carbohydrate chemistry and biochemistry . [ 3 ] This coming together was as a result of a much greater understanding of the cellular and molecular biology of glycans . However, as early as the late nineteenth century pioneering efforts were being made by Emil Fisher to establish the structure of some basic sugar molecules. Each year the Society of Glycobiology awards the Rosalind Kornfeld award for lifetime achievement in the field of glycobiology. [ 4 ]
Sugars may be linked to other types of biological molecule to form glycoconjugates. The enzymatic process of glycosylation creates sugars/saccharides linked to themselves and to other molecules by the glycosidic bond, thereby producing glycans. Glycoproteins , proteoglycans and glycolipids are the most abundant glycoconjugates found in mammalian cells. They are found predominantly on the outer cell membrane and in secreted fluids. Glycoconjugates have been shown to be important in cell-cell interactions due to the presence on the cell surface of various glycan binding receptors in addition to the glycoconjugates themselves. [ 5 ] [ 6 ] In addition to their function in protein folding and cellular attachment, the N-linked glycans of a protein can modulate the protein's function, in some cases acting as an on-off switch. [ 7 ]
" Glycomics , analogous to genomics and proteomics , is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology. [ 8 ] [ 9 ]
Part of the variability seen in saccharide structures is because monosaccharide units may be coupled to each other in many different ways, as opposed to the amino acids of proteins or the nucleotides in DNA , which are always coupled together in a standard fashion. [ 10 ] The study of glycan structures is also complicated by the lack of a direct template for their biosynthesis, contrary to the case with proteins where their amino acid sequence is determined by their corresponding gene . [ 11 ]
Glycans are secondary gene products and therefore are generated by the coordinated action of many enzymes in the subcellular compartments of a cell. Since the structure of a glycan may depend on the expression , activity and accessibility of the different biosynthetic enzymes, it is not possible to use recombinant DNA technology in order to produce large quantities of glycans for structural and functional studies as it is for proteins.
Advanced analytical instruments and software programs, when used in combination, can unlock the mystery of glycan structures. Current techniques for structural annotation and analysis of glycans include liquid chromatography (LC), capillary electrophoresis (CE), mass spectrometry (MS), nuclear magnetic resonance (NMR) and lectin arrays. [ 12 ]
One of the most widely used techniques is mass spectrometry which uses three principal units: the ionizer, analyzer and detector.
Glycan arrays, like that offered by the Consortium for Functional Glycomics and Z Biotech LLC, contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands.
MRM is a mass spectrometry-based technique that has recently been used for site-specific glycosylation profiling. Although MRM has been used extensively in metabolomics and proteomics, its high sensitivity and linear response over a wide dynamic range make it especially suited for glycan biomarker research and discovery. MRM is performed on a triple quadrupole (QqQ) instrument, which is set to detect a predetermined precursor ion in the first quadrupole, a fragmented in the collision quadrupole, and a predetermined fragment ion in the third quadrupole. It is a non-scanning technique, wherein each transition is detected individually and the detection of multiple transitions occurs concurrently in duty cycles. [ 7 ] This technique is being used to characterize the immune glycome. [ 7 ]
Drugs already on the market, such as heparin , erythropoietin and a few anti-flu drugs, have proven effective and highlight the importance of glycans as a new class of drug. Additionally, the search for new anti-cancer drugs is opening up new possibilities in glycobiology. [ 13 ] Anti-cancer drugs with new and varied action mechanisms together with anti-inflammatory and anti-infection drugs are today undergoing clinical trials. They may alleviate or complete current therapies. Although these glycans are molecules that are difficult to synthesize in a reproducible way, owing to their complex structure, this new field of research is highly encouraging for the future.
Glycobiology, in which recent developments have been made possible by the latest technological advances, helps provide a more specific and precise understanding of skin aging.
It has now been clearly established that glycans are major constituents of the skin and play a decisive role in skin homeostasis.
Vital to the proper functioning of skin, glycans undergo both qualitative and quantitative changes in the course of aging. [ 15 ] The functions of communication and metabolism are impaired and the skin's architecture is degraded. | https://en.wikipedia.org/wiki/Glycobiology |
Glycobiology is a monthly peer-reviewed scientific journal covering all aspects of the field of glycobiology and the official journal of the Society for Glycobiology . [ 1 ] It is published by Oxford University Press . The journal was established in September 1990. It publishes primary research on the "biological functions of glycans , including glycoproteins , glycolipids , proteoglycans and free oligosaccharides , and on proteins that specifically interact with glycans." [ 1 ]
The journal is indexed in Index Medicus / PubMed / MEDLINE , Index Veterinarius , CAB Abstracts , Biological Abstracts , BIOSIS Previews , Current Contents /Life Sciences, ProQuest , Science Citation Index , and others. [ 2 ] According to the Journal Citation Reports , its 2019 impact factor is 4.060, ranking it 102nd out of 297 journals in the category "Biochemistry & Molecular Biology". [ 2 ] | https://en.wikipedia.org/wiki/Glycobiology_(journal) |
The glycocalyx ( pl. : glycocalyces or glycocalyxes ), also known as the pericellular matrix and cell coat , is a layer of glycoproteins and glycolipids which surround the cell membranes of bacteria , epithelial cells , and other cells. [ 1 ]
Animal epithelial cells have a fuzz-like coating on the external surface of their plasma membranes . This viscous coating is the glycocalyx that consists of several carbohydrate moieties of membrane glycolipids and glycoproteins , which serve as backbone molecules for support. Generally, the carbohydrate portion of the glycolipids found on the surface of plasma membranes helps these molecules contribute to cell–cell recognition , communication, and intercellular adhesion. [ 2 ]
The glycocalyx is a type of identifier that the body uses to distinguish between its own healthy cells and transplanted tissues, diseased cells, or invading organisms. Included in the glycocalyx are cell-adhesion molecules that enable cells to adhere to each other and guide the movement of cells during embryonic development. [ 3 ] The glycocalyx plays a major role in regulation of endothelial vascular tissue , including the modulation of red blood cell volume in capillaries . [ 4 ]
The term was initially applied to the polysaccharide matrix coating epithelial cells, but its functions have been discovered to go well beyond that.
The glycocalyx is located on the apical surface of vascular endothelial cells which line the lumen . When vessels are stained with cationic dyes such as Alcian blue stain , transmission electron microscopy shows a small, irregularly shaped layer extending approximately 50–100 nm into the lumen of a blood vessel. Another study used osmium tetroxide staining during freeze substitution, and showed that the endothelial glycocalyx could be up to 11 μm thick. [ 5 ] It is present throughout a diverse range of microvascular beds (capillaries) and macrovessels (arteries and veins). The glycocalyx also consists of a wide range of enzymes and proteins that regulate leukocyte and thrombocyte adherence, since its principal role in the vasculature is to maintain plasma and vessel-wall homeostasis. These enzymes and proteins include:
The enzymes and proteins listed above serve to reinforce the glycocalyx barrier against vascular and other diseases. Another main function of the glycocalyx within the vascular endothelium is that it shields the vascular walls from direct exposure to blood flow, while serving as a vascular permeability barrier. [ 6 ] Its protective functions are universal throughout the vascular system, but its relative importance varies depending on its exact location in the vasculature. In microvascular tissue, the glycocalyx serves as a vascular permeability barrier by inhibiting coagulation and leukocyte adhesion. Leukocytes must not stick to the vascular wall because they are important components of the immune system that must be able to travel to a specific region of the body when needed. In arterial vascular tissue, the glycocalyx also inhibits coagulation and leukocyte adhesion, but through mediation of shear stress -induced nitric oxide release. Another protective function throughout the cardiovascular system is its ability to affect the filtration of interstitial fluid from capillaries into the interstitial space. [ 7 ]
The glycocalyx, which is located on the apical surface of endothelial cells, is composed of a negatively charged network of proteoglycans , glycoproteins, and glycolipids. [ 8 ] Along the luminal surface of the vascular glycocalyx exists an empty layer that excludes red blood cells. [ 9 ]
Because the glycocalyx is so prominent throughout the cardiovascular system, disruption to this structure has detrimental effects that can cause disease. Certain stimuli that cause atheroma may lead to enhanced sensitivity of vasculature. Initial dysfunction of the glycocalyx can be caused by hyperglycemia or oxidized low-density lipoproteins ( LDLs ), which then causes atherothrombosis . In microvasculature, dysfunction of the glycocalyx leads to internal fluid imbalance, and potentially edema . In arterial vascular tissue, glycocalyx disruption causes inflammation and atherothrombosis. [ 10 ]
Experiments have been performed to test precisely how the glycocalyx can be altered or damaged. One particular study used an isolated perfused heart model designed to facilitate detection of the state of the vascular barrier portion, and sought to cause insult-induced shedding of the glycocalyx to ascertain the cause-and-effect relationship between glycocalyx shedding and vascular permeability. Hypoxic perfusion of the glycocalyx was thought to be sufficient to initiate a degradation mechanism of the endothelial barrier. The study found that flow of oxygen throughout the blood vessels did not have to be completely absent ( ischemic hypoxia), but that minimal [ clarification needed ] levels of oxygen were sufficient to cause the degradation. Shedding of the glycocalyx can be triggered by inflammatory stimuli, such as tumor necrosis factor-alpha . Whatever the stimulus is, however, shedding of the glycocalyx leads to a drastic [ clarification needed ] increase in vascular permeability. Vascular walls being permeable is disadvantageous, since that would enable passage of some macromolecules or other harmful antigens. [ 11 ]
Other sources of damage to the endothelial glycocalyx have been observed in several pathological conditions such as inflammation, [ 12 ] hyperglycemia, [ 13 ] ischemia-reperfusion, [ 14 ] viral infections [ 15 ] and sepsis. [ 16 ]
Some key components of the glycocalyx such as syndecans , heparan sulphate , chondroitin sulphate and hyaluronan can be shed of the endothelial layer by enzymes. Hyaluronidase , hepararanse/heparinase, matrix and membrane-type matrix metalloproteases , thrombin, plasmin and elastase are some examples of enzymes that can induce shedding of the glycocalyx and these sheddases can therefor contribute to degradation of the glycocalyx layer in several pathological conditions. [ 17 ] Research shows that plasma hyaluronidase activity is decreased in experimental as well as in clinical septic shock and is therefore not considered to be a sheddase in sepsis. [ 18 ] Concomitant, the endogenous plasma inhibition of hyaluronidase is increased and could serve as a protection against glycocalyx shedding.
Fluid shear stress is also a potential problem if the glycocalyx is degraded for any reason. This type of frictional stress is caused by the movement of viscous fluid (i.e. blood) along the lumen boundary. Another similar experiment was carried out to determine what kinds of stimuli cause fluid shear stress. The initial measurement was taken with intravital microscopy, which showed a slow-moving plasma layer, the glycocalyx, of 1 μm thick. Light dye damaged the glycocalyx minimally, but that small change increased capillary hematocrit . Thus, fluorescence light microscopy should not be used to study the glycocalyx because that particular method uses a dye. The glycocalyx can also be reduced in thickness when treated with oxidized LDL. [ 19 ] These stimuli, along with many other factors, can cause damage to the delicate glycocalyx. These studies are evidence that the glycocalyx plays a crucial role in cardiovascular system health.
A glycocalyx, literally meaning "sugar coat" ( glykys = sweet, kalyx = husk), is a network of polysaccharides that project from cellular surfaces of bacteria , which classifies it as a universal surface component of a bacterial cell, found just outside the bacterial cell wall. A distinct, gelatinous glycocalyx is called a capsule , whereas an irregular, diffuse layer is called a slime layer . This coat is extremely hydrated and stains with ruthenium red .
Bacteria growing in natural ecosystems, such as in soil, bovine intestines, or the human urinary tract, are surrounded by some sort of glycocalyx-enclosed microcolony . [ 20 ] It serves to protect the bacterium from harmful phagocytes by creating capsules or allowing the bacterium to attach itself to inert surfaces, such as teeth or rocks, via biofilms (e.g. Streptococcus pneumoniae attaches itself to either lung cells, prokaryotes , or other bacteria which can fuse their glycocalices to envelop the colony).
A glycocalyx can also be found on the apical portion of microvilli within the digestive tract , especially within the small intestine. It creates a meshwork 0.3 μm thick and consists of acidic mucopolysaccharides and glycoproteins that project from the apical plasma membrane of epithelial absorptive cells. It provides additional surface for adsorption and includes enzymes secreted by the absorptive cells that are essential for the final steps of digestion of proteins and sugars. | https://en.wikipedia.org/wiki/Glycocalyx |
In molecular biology and biochemistry , glycoconjugates are the classification family for carbohydrates – referred to as glycans – which are covalently linked with chemical species such as proteins , peptides , lipids , and other compounds. [ 1 ] Glycoconjugates are formed in processes termed glycosylation .
Glycoconjugates are very important compounds in biology and consist of many different categories such as glycoproteins , glycopeptides , peptidoglycans , glycolipids , glycosides , and lipopolysaccharides . They are involved in cell –cell interactions, including cell–cell recognition ; in cell– matrix interactions; and in detoxification processes.
Generally, the carbohydrate part(s) play an integral role in the function of a glycoconjugate; prominent examples of this are neural cell adhesion molecule (NCAM) and blood proteins where fine details in the carbohydrate structure determine cell binding (or not) or lifetime in circulation.
Although the important molecular species DNA , RNA , ATP , cAMP , cGMP , NADH , NADPH , and coenzyme A all contain a carbohydrate part, generally they are not considered as glycoconjugates.
Glycocojugates of carbohydrates covalently linked to antigens and protein scaffolds can achieve a long term immunological response in the body. [ 2 ] Immunization with glycoconjugates successfully induced long term immune memory against carbohydrates antigens. Glycoconjugate vaccines was introduced since the 1990s have yielded effective results against influenza and meningococcus . [ 3 ]
In 2021 glycoRNAs were observed for the first time. [ 4 ] [ 5 ] [ 6 ]
This pharmacology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glycoconjugate |
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals , [ 2 ] fungi , and bacteria. [ 3 ] It is the main storage form of glucose in the human body.
Glycogen functions as one of three regularly used forms of energy reserves, creatine phosphate being for very short-term, glycogen being for short-term and the triglyceride stores in adipose tissue (i.e., body fat) being for long-term storage. Protein, broken down into amino acids, is seldom used as a main energy source except during starvation and glycolytic crisis (see bioenergetic systems ) .
In humans , glycogen is made and stored primarily in the cells of the liver and skeletal muscle . [ 4 ] [ 5 ] In the liver, glycogen can make up 5–6% of the organ's fresh weight: the liver of an adult, weighing 1.5 kg, can store roughly 100–120 grams of glycogen. [ 4 ] [ 6 ] In skeletal muscle, glycogen is found in a low concentration (1–2% of the muscle mass): the skeletal muscle of an adult weighing 70 kg stores roughly 400 grams of glycogen. [ 4 ] Small amounts of glycogen are also found in other tissues and cells, including the kidneys , red blood cells , [ 7 ] [ 8 ] [ 9 ] white blood cells , [ 10 ] and glial cells in the brain . [ 11 ] The uterus also stores glycogen during pregnancy to nourish the embryo. [ 12 ]
The amount of glycogen stored in the body mostly depends on oxidative type 1 fibres , [ 13 ] [ 14 ] physical training, basal metabolic rate , and eating habits. [ 15 ] Different levels of resting muscle glycogen are reached by changing the number of glycogen particles, rather than increasing the size of existing particles [ 14 ] though most glycogen particles at rest are smaller than their theoretical maximum. [ 16 ]
Approximately 4 grams of glucose are present in the blood of humans at all times; [ 4 ] in fasting individuals, blood glucose is maintained constant at this level at the expense of glycogen stores, primarily from the liver (glycogen in skeletal muscle is mainly used as an immediate source of energy for that muscle rather than being used to maintain physiological blood glucose levels). [ 4 ] Glycogen stores in skeletal muscle serve as a form of energy storage for the muscle itself; [ 4 ] however, the breakdown of muscle glycogen impedes muscle glucose uptake from the blood, thereby increasing the amount of blood glucose available for use in other tissues. [ 4 ] Liver glycogen stores serve as a store of glucose for use throughout the body, particularly the central nervous system . [ 4 ] The human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals. [ 4 ]
Glycogen is an analogue of starch , a glucose polymer that functions as energy storage in plants . It has a structure similar to amylopectin (a component of starch), but is more extensively branched and compact than starch. Both are white powders in their dry state. Glycogen is found in the form of granules in the cytosol /cytoplasm in many cell types, and plays an important role in the glucose cycle . Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose, but one that is less compact than the energy reserves of triglycerides ( lipids ). As such it is also found as storage reserve in many parasitic protozoa. [ 17 ] [ 18 ] [ 19 ]
Glycogen is a branched biopolymer consisting of linear chains of glucose residues with an average chain length of approximately 8–12 glucose units and 2,000-60,000 residues per one molecule of glycogen. [ 20 ] [ 21 ]
Like amylopectin, glucose units are linked together linearly by α(1→4) glycosidic bonds from one glucose to the next. Branches are linked to the chains from which they are branching off by α(1→6) glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain. [ 22 ]
Each glycogen is essentially a ball of glucose trees, with around 12 layers, centered on a glycogenin protein, with three kinds of glucose chains: A, B, and C. There is only one C-chain, attached to the glycogenin. This C-chain is formed by the self-glucosylation of the glycogenin, forming a short primer chain. From the C-chain grows out B-chains, and from B-chains branch out B- and A-chains. The B-chains have on average 2 branch points, while the A-chains are terminal, thus unbranched. On average, each chain has length 12, tightly constrained to be between 11 and 15. All A-chains reach the spherical surface of the glycogen. [ 23 ] [ 24 ]
Glycogen in muscle, liver, and fat cells is stored in a hydrated form, composed of three or four parts of water per part of glycogen associated with 0.45 millimoles (18 mg) of potassium per gram of glycogen. [ 5 ]
Glucose is an osmotic molecule, and can have profound effects on osmotic pressure in high concentrations possibly leading to cell damage or death if stored in the cell without being modified. [ 3 ] Glycogen is a non-osmotic molecule, so it can be used as a solution to storing glucose in the cell without disrupting osmotic pressure. [ 3 ]
As a meal containing carbohydrates or protein is eaten and digested , blood glucose levels rise, and the pancreas secretes insulin . Blood glucose from the portal vein enters liver cells ( hepatocytes ). Insulin acts on the hepatocytes to stimulate the action of several enzymes , including glycogen synthase . Glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful. In this postprandial or "fed" state, the liver takes in more glucose from the blood than it releases.
After a meal has been digested and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. When it is needed for energy , glycogen is broken down and converted again to glucose. Glycogen phosphorylase is the primary enzyme of glycogen breakdown. For the next 8–12 hours, glucose derived from liver glycogen is the primary source of blood glucose used by the rest of the body for fuel.
Glucagon , another hormone produced by the pancreas, in many respects serves as a countersignal to insulin. In response to insulin levels being below normal (when blood levels of glucose begin to fall below the normal range), glucagon is secreted in increasing amounts and stimulates both glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the production of glucose from other sources).
Muscle glycogen appears to function as a reserve of quickly available phosphorylated glucose, in the form of glucose-1-phosphate , for muscle cells. Glycogen contained within skeletal muscle cells are primarily in the form of β particles. [ 25 ] Other cells that contain small amounts use it locally as well. As muscle cells lack glucose-6-phosphatase , which is required to pass glucose into the blood, the glycogen they store is available solely for internal use and is not shared with other cells. This is in contrast to liver cells, which, on demand, readily do break down their stored glycogen into glucose and send it through the blood stream as fuel for other organs. [ 26 ]
Skeletal muscle needs ATP (provides energy) for muscle contraction and relaxation, in what is known as the sliding filament theory . Skeletal muscle relies predominantly on glycogenolysis for the first few minutes as it transitions from rest to activity, as well as throughout high-intensity aerobic activity and all anaerobic activity. [ 27 ] During anaerobic activity, such as weightlifting and isometric exercise , the phosphagen system (ATP-PCr) and muscle glycogen are the only substrates used as they do not require oxygen nor blood flow. [ 27 ]
Different bioenergetic systems produce ATP at different speeds, with ATP produced from muscle glycogen being much faster than fatty acid oxidation. [ 28 ] The level of exercise intensity determines how much of which substrate (fuel) is used for ATP synthesis also. Muscle glycogen can supply a much higher rate of substrate for ATP synthesis than blood glucose. During maximum intensity exercise, muscle glycogen can supply 40 mmol glucose/kg wet weight/minute, [ 29 ] whereas blood glucose can supply 4 - 5 mmol. [ 30 ] [ 4 ] Due to its high supply rate and quick ATP synthesis, during high-intensity aerobic activity (such as brisk walking, jogging, or running), the higher the exercise intensity, the more the muscle cell produces ATP from muscle glycogen. [ 31 ] This reliance on muscle glycogen is not only to provide the muscle with enough ATP during high-intensity exercise, but also to maintain blood glucose homeostasis (that is, to not become hypoglycaemic by the muscles needing to extract far more glucose from the blood than the liver can provide). [ 30 ] A deficit of muscle glycogen leads to muscle fatigue known as "hitting the wall" or "the bonk" (see below under glycogen depletion) .
In 1999, Meléndez et al claimed that the structure of glycogen is optimal under a particular metabolic constraint model, where the structure was suggested to be "fractal" in nature. [ 32 ] However, research by Besford et al [ 33 ] used small angle X-ray scattering experiments accompanied by branching theory models to show that glycogen is a randomly hyperbranched polymer nanoparticle. Glycogen is not fractal in nature. This has been subsequently verified by others who have performed Monte Carlo simulations of glycogen particle growth, and shown that the molecular density reaches a maximum near the centre of the nanoparticle structure, not at the periphery (contradicting a fractal structure that would have greater density at the periphery). [ 34 ]
Glycogen was discovered by Claude Bernard . His experiments showed that the liver contained a substance that could give rise to reducing sugar by the action of a "ferment" in the liver. By 1857, he described the isolation of a substance he called " la matière glycogène ", or "sugar-forming substance". Soon after the discovery of glycogen in the liver, M.A. Sanson found that muscular tissue also contains glycogen. The empirical formula for glycogen of ( C 6 H 10 O 5 ) n was established by August Kekulé in 1858. [ 35 ]
Sanson, M. A. "Note sur la formation physiologique du sucre dans l’economie animale." Comptes rendus des seances de l’Academie des Sciences 44 (1857): 1323-5.
Glycogen synthesis is, unlike its breakdown, endergonic —it requires the input of energy. Energy for glycogen synthesis comes from uridine triphosphate (UTP), which reacts with glucose-1-phosphate , forming UDP-glucose , in a reaction catalysed by UTP—glucose-1-phosphate uridylyltransferase . Glycogen is synthesized from monomers of UDP-glucose initially by the protein glycogenin , which has two tyrosine anchors for the reducing end of glycogen, since glycogenin is a homodimer. After about eight glucose molecules have been added to a tyrosine residue, the enzyme glycogen synthase progressively lengthens the glycogen chain using UDP-glucose, adding α(1→4)-bonded glucose to the nonreducing end of the glycogen chain. [ 36 ]
The glycogen branching enzyme catalyzes the transfer of a terminal fragment of six or seven glucose residues from a nonreducing end to the C-6 hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule. The branching enzyme can act upon only a branch having at least 11 residues, and the enzyme may transfer to the same glucose chain or adjacent glucose chains.
Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate:
In vivo, phosphorolysis proceeds in the direction of glycogen breakdown because the ratio of phosphate and glucose-1-phosphate is usually greater than 100. [ 37 ] Glucose-1-phosphate is then converted to glucose 6 phosphate (G6P) by phosphoglucomutase . A special debranching enzyme is needed to remove the α(1→6) branches in branched glycogen and reshape the chain into a linear polymer. The G6P monomers produced have three possible fates:
The most common disease in which glycogen metabolism becomes abnormal is diabetes , in which, because of abnormal amounts of insulin, liver glycogen can be abnormally accumulated or depleted. Restoration of normal glucose metabolism usually normalizes glycogen metabolism, as well.
In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but the high insulin levels prevent the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia.
Various inborn errors of carbohydrate metabolism are caused by deficiencies of enzymes or transport proteins necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases .
Long-distance athletes, such as marathon runners, cross-country skiers , and cyclists , often experience glycogen depletion, where almost all of the athlete's glycogen stores are depleted after long periods of exertion without sufficient carbohydrate consumption. This phenomenon is referred to as " hitting the wall " in running and "bonking" in cycling.
Glycogen depletion can be forestalled in three possible ways:
When athletes ingest both carbohydrate and caffeine following exhaustive exercise, their glycogen stores tend to be replenished more rapidly; [ 45 ] [ 46 ] however, the minimum dose of caffeine at which there is a clinically significant effect on glycogen repletion has not been established. [ 46 ]
Glycogen nanoparticles have been investigated as potential drug delivery systems . [ 47 ] | https://en.wikipedia.org/wiki/Glycogen |
4BZY , 5CLT , 5CLW
2632
74185
ENSG00000114480
ENSMUSG00000022707
Q04446
Q9D6Y9
NM_000158
NM_028803
NP_000149
NP_083079
1,4-alpha-glucan-branching enzyme , also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the GBE1 gene . [ 5 ]
Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecule during the synthesis of glycogen , a storage form of glucose . More specifically, during glycogen synthesis, a glucose 1-phosphate molecule reacts with uridine triphosphate (UTP) to become UDP-glucose, an activated form of glucose. The activated glucosyl unit of UDP-glucose is then transferred to the hydroxyl group at the C-4 of a terminal residue of glycogen to form an α-1,4- glycosidic linkage , a reaction catalyzed by glycogen synthase . Importantly, glycogen synthase can only catalyze the synthesis of α-1,4-glycosidic linkages. Since glycogen is a readily mobilized storage form of glucose, the extended glycogen polymer is branched by glycogen branching enzyme to provide glycogen breakdown enzymes, such as glycogen phosphorylase , with many terminal residues for rapid degradation. Branching also importantly increases the solubility and decreases the osmotic strength of glycogen. [ 6 ]
The protein encoded by this gene is a glycogen branching enzyme that catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, in reducing the osmotic pressure within cells . The highest levels of this enzyme are found in liver and muscle cells. Mutations in this gene are associated with glycogen storage disease type IV (also known as Andersen's disease).
This enzyme belongs to the family of transferases , to be specific, those glycosyltransferases that transfer hexoses ( hexosyltransferases ). The systematic name of this enzyme class is 1,4-alpha-D-glucan:1,4-alpha-D-glucan 6-alpha-D-(1,4-alpha-D-glucano)-transferase. Other names in common use include branching enzyme, amylo-(1,4→1,6)-transglycosylase, Q-enzyme, alpha-glucan-branching glycosyltransferase, amylose isomerase, enzymatic branching factor, branching glycosyltransferase, enzyme Q, glucosan transglycosylase, 1,4-alpha-glucan branching enzyme 1 , plant branching enzyme, alpha-1,4-glucan:alpha-1,4-glucan-6-glycosyltransferase, and starch branching enzyme. This enzyme participates in starch and sucrose metabolism.
GBE is encoded by the GBE1 gene . [ 5 ] [ 7 ] [ 8 ] [ 9 ]
Through Southern blot analysis of DNA derived from human/rodent somatic cell hybrids, GBE1 has been identified as an autosomal gene located on the short arm of chromosome 3 at position 12.3. [ 7 ] [ 8 ] [ 9 ] [ 10 ] The human GBE gene was also isolated by a function complementation of the Saccharomyces cerevisiae GBE deficiency. [ 10 ] From the isolated cDNA, the length of the gene was found to be approximately 3 kb. [ 10 ] Additionally, the coding sequence was found to comprise 2,106 base pairs and encode a 702-amino acid long GBE. The molecular mass of human GBE was calculated to be 80,438 Da. [ 10 ]
Glycogen branching enzyme belongs to the α-amylase family of enzymes, which include α-amylases, pullulanas/isoamylase, cyclodextrin glucanotransferase (CGT), and branching enzyme. [ 11 ] [ 12 ] Shown by x-ray crystallography, glycogen branching enzyme has four marginally asymmetric units each that are organized into three domains: an amino-terminal domain, involved in determining the length of the chain transfer, a carboxyl-terminal domain, involved in substrate preference and catalytic capacity, and a central (α/β) barrel catalytic domain. [ 11 ] [ 13 ] [ 14 ] [ 15 ] The amino-terminal domain consists of 128 residues arranged in seven β-strands, the carboxyl-terminal domain with 116 residues also organized in seven β-strands, and the (α/β) barrel domain with 372 residues. While the central (α/β) barrel domain is common in members of the α-amylase family, numerous variations exist between the various barrel domains. Additionally, there are striking differences between the loops connecting elements of the secondary structure among these various α-amylase members, especially around the active site. In comparison to the other family members, glycogen binding enzyme has shorter loops, which result in a more open cavity, favorable to the binding of a bulkier substrate such as branched sugar. Through primary structure analysis and the x-ray crystallographic structures of the members of the α-amylase family, seven residue were conserved, Asp335, His340, Arg403, Asp 405, Glu458, His525, and Asp526 (E coli. numbering). These residues are implicated in catalysis and substrate binding. [ 11 ]
Glycogen binding enzymes in other organisms have also been crystallized and structurally determined, demonstrating both similarity and variation to GBE found in Escherichia coli . [ 16 ] [ 17 ] [ 18 ] [ 19 ]
In glycogen , every 10 to 14 glucose units, a side branch with an additional chain of glucose units occurs. The side chain attaches at carbon atom 6 of a glucose unit, an α-1,6-glycosidic bond. This connection is catalyzed by a branching enzyme, generally given the name α-glucan branching enzyme. A branching enzyme attaches a string of seven glucose units (with some minor variation to this number) to the carbon at the C-6 position on the glucose unit, forming the α-1,6-glycosidic bond. The specific nature of this enzyme means that this chain of 7 carbons is usually attached to a glucose molecule that is in position three from the non-reducing end of another chain. Because the enzyme works with such specificity regarding the number of glucose units transferred and the position to which they are transferred, the enzyme creates the very characteristic, highly branched glycogen molecule. [ 20 ]
Mutations in this gene are associated with glycogen storage disease type IV (also known as Andersen's disease) in newborns and with adult polyglucosan body disease . [ 5 ] [ 21 ]
Approximately 40 mutations in the GBE1 gene, most resulting in a point mutation in the glycogen branching enzyme, have led to the early childhood disorder, glycogen storage disease type IV (GSD IV). [ 9 ] This disease is characterized by a severe depletion or complete absence of GBE, resulting in the accumulation of abnormally structured glycogen, known as polyglucosan bodies. [ 9 ] Glycogen buildup leads to increased osmotic pressure resulting in cellular swelling and death. [ 9 ] The tissues most affected by this disease are the liver, heart, and neuromuscular system, areas with the greatest levels of glycogen accumulation. [ 9 ] [ 22 ] Abnormal glycogen buildup in the liver interferes with liver functioning and can result in an enlarged liver and liver disease. [ 9 ] [ 23 ] In muscles, the inability of cells to efficiently breakdown glycogen due to the severe reduction or absence of branching can lead to muscle weakness and atrophy. [ 9 ] At least three mutations in the GBE1 gene have been found to cause another disease called adult polyglucosan body disease (APBD). [ 9 ] [ 24 ] While in GSD IV GBE activity is undetectable or minimally detectable, APBD is characterized by reduced or even normal GBE activity. [ 24 ] In this disease, abnormal glycogen can build up in neurons leading to a spectrum of problems. Specifically, some disease characteristics are gait difficulties from mixed upper and lower motor neuron involvement sensory loss in lower extremities, and neurogenic bladder , a problem in which a person lacks bladder control due to a brain, spinal cord, or nerve condition. [ 24 ] [ 25 ] | https://en.wikipedia.org/wiki/Glycogen_branching_enzyme |
178
77559
ENSG00000162688
ENSMUSG00000033400
P35573
n/a
NM_000646
NM_001081326 NM_001362367
NP_000019 NP_000633 NP_000634 NP_000635 NP_000637
n/a
The glycogen debranching enzyme , in humans, is the protein encoded by the gene AGL . [ 5 ] This enzyme is essential for the breakdown of glycogen , which serves as a store of glucose in the body. It has separate glucosyltransferase and glucosidase activities. [ 6 ] [ 7 ]
Together with phosphorylases , the enzyme mobilize glucose reserves from glycogen deposits in the muscles and liver. This constitutes a major source of energy reserves in most organisms. Glycogen breakdown is highly regulated in the body, especially in the liver , by various hormones including insulin and glucagon , to maintain a homeostatic balance of blood-glucose levels. [ 8 ] When glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as Glycogen storage disease type III can result. [ 6 ] [ 7 ]
The two steps of glycogen breakdown, glucosyltransferase and glucosidase, are performed by a single enzyme in mammals, yeast, and some bacteria, but by two distinct enzymes in E. coli and other bacteria, complicating nomenclature. Proteins that catalyze both functions are referred to as glycogen debranching enzymes (GDEs). When glucosyltransferase and glucosidase are catalyzed by distinct enzymes, glycogen debranching enzyme usually refers to the glucosidase enzyme . In some literature, an enzyme capable only of glucosidase is referred to as a debranching enzyme . [ 9 ]
Together with phosphorylase , glycogen debranching enzymes function in glycogen breakdown and glucose mobilization. When phosphorylase has digested a glycogen branch down to four glucose residues, it will not remove further residues. Glycogen debranching enzymes assist phosphorylase, the primary enzyme involved in glycogen breakdown , in the mobilization of glycogen stores. Phosphorylase can only cleave α-1,4-glycosidic bond between adjacent glucose molecules in glycogen but branches also exist as α-1,6 linkages. When phosphorylase reaches four residues from a branching point it stops cleaving; because 1 in 10 residues is branched, cleavage by phosphorylase alone would not be sufficient in mobilizing glycogen stores. [ 10 ] [ 11 ] Before phosphorylase can resume catabolism, debranching enzymes perform two functions:
Thus the debranching enzymes, transferase and α-1,6-glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase.
In E. coli and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct proteins. In E. coli , Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ. [ 14 ] A second protein, referred to as debranching enzyme, performs α-1,6-glucose cleavage. This enzyme has a molecular mass of 73.6 kDa, and is coded for by the gene glgX. [ 15 ] Activity of the two enzymes is not always necessarily coupled. In E. coli glgX selectively catalyzes the cleavage of 4-subunit branches, without the action of glucanotransferase. The product of this cleavage, maltotetraose , is further degraded by maltodextrin phosphorylase. [ 6 ] [ 16 ]
E. coli GlgX is structurally similar to the protein isoamylase . The monomeric protein contains a central domain in which eight parallel beta-strands are surrounded by eight parallel alpha strands. Notable within this structure is a groove 26 angstroms long and 9 angstroms wide, containing aromatic residues that are thought to stabilize a four-glucose branch before cleavage. [ 6 ]
The glycogen-degrading enzyme of the archaea Sulfolobus solfataricus , treX, provides an interesting example of using a single active site for two activities: amylosidase and glucanotransferase activities. TreX is structurally similar to glgX, and has a mass of 80kD and one active site. [ 9 ] [ 17 ] Unlike either glgX, however, treX exists as a dimer and tetramer in solution. TreX's oligomeric form seems to play a significant role in altering both enzyme shape and function. Dimerization is thought to stabilize a "flexible loop" located close to the active site. This may be key to explaining why treX (and not glgX) shows glucosyltransferase activity. As a tetramer, the catalytic efficiency of treX is increased fourfold over its dimeric form. [ 6 ] [ 18 ]
In mammals and yeast , a single enzyme performs both debranching functions. [ 19 ] The human glycogen debranching enzyme (gene: AGL) is a monomer with a molecular weight of 175 kDa. It has been shown that the two catalytic actions of AGL can function independently of each other, demonstrating that multiple active sites are present. This idea has been reinforced with inhibitors of the active site, such as polyhydroxyamine, which were found to inhibit glucosidase activity while transferase activity was not measurably changed. [ 20 ] Glycogen debranching enzyme is the only known eukaryotic enzyme that contains multiple catalytic sites and is active as a monomer. [ 21 ] [ 22 ]
Some studies have shown that the C-terminal half of yeast GDE is associated with glucosidase activity, while the N-terminal half is associated with glucosyltransferase activity. [ 19 ] In addition to these two active sites , AGL appears to contain a third active site that allows it to bind to a glycogen polymer. [ 23 ] It is thought to bind to six glucose molecules of the chain as well as the branched glucose, thus corresponding to 7 subunits within the active site, as shown in the figure below. [ 24 ]
The structure of the Candida glabrata GDE has been reported. [ 25 ] The structure revealed that distinct domains in GDE encode the glucanotransferase and glucosidase activities. Their catalyses are similar to that of alpha-amylase and glucoamylase, respectively. Their active sites are selective towards the respective substrates, ensuring proper activation of GDE. Besides the active sites GDE have additional binding sites for glycogen, which are important for its recruitment to glycogen. Mapping the disease-causing mutations onto the GDE structure provided insights into glycogen storage disease type III.
The official name for the gene is "amylo-α-1,6-glucosidase, 4-α-glucanotransferase", with the official symbol AGL. AGL is an autosomal gene found on chromosome 1p21. [ 11 ] The AGL gene provides instructions for making several different versions, known as isoforms, of the glycogen debranching enzyme. These isoforms vary by size and are expressed in different tissues, such as liver and muscle. This gene has been studied in great detail, because mutation at this gene is the cause of Glycogen Storage Disease Type III. [ 5 ] The gene is 85 kb long, has 35 exons and encodes for a 7.0 kb mRNA. Translation of the gene begins at exon 3, which encodes for the first 27 amino acids of the AGL gene, because the first two exons (68kb) contain the 5' untranslated region. Exons 4-35 encode the remaining 1505 amino acids of the AGL gene. [ 7 ] Studies produced by the department of pediatrics at Duke University suggest that the human AGL gene contains at minimum 2 promotor regions, sites where the transcription of the gene begins, that result in differential expression of isoform, different forms of the same protein, mRNAs in a manner that is specific for different tissues. [ 23 ] [ 26 ]
When GDE activity is compromised, the body cannot effectively release stored glycogen, type III Glycogen Storage Disease (debrancher deficiency), an autosomal recessive disorder, can result. In GSD III glycogen breakdown is incomplete and there is accumulation of abnormal glycogen with short outer branches. [ 27 ]
Most patients exhibit GDE defiency in both liver and muscle (Type IIIa), although 15% of patients have retained GDE in muscle while having it absent from the liver (Type IIIb). [ 11 ] Depending on mutation location, different mutations in the AGL gene can affect different isoforms of the gene expression . For example, mutations that occur on exon 3, affect the form which affect the isoform that is primarily expressed in the liver; this would lead to GSD type III. [ 28 ]
These different manifestation produce varied symptoms, which can be nearly indistinguishable from Type I GSD, including hepatomegaly , hypoglycemia in children, short stature, myopathy , and cardiomyopathy . [ 7 ] [ 29 ] Type IIIa patients often exhibit symptoms related to liver disease and progressive muscle involvement, with variations caused by age of onset, rate of disease progression and severity. Patients with Type IIIb generally symptoms related to liver disease. [ 30 ] Type III patients be distinguished by elevated liver enzymes, with normal uric acid and blood lactate levels, differing from other forms of GSD. [ 28 ] In patients with muscle involvement, Type IIIa, the muscle weakness becomes predominant into adulthood and can lead to ventricular hypertrophy and distal muscle wasting. [ 28 ] | https://en.wikipedia.org/wiki/Glycogen_debranching_enzyme |
Glycogen phosphorylase is one of the phosphorylase enzymes ( EC 2.4.1.1 ). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.
Glycogen phosphorylase breaks up glycogen into glucose subunits (see also figure below):
(α-1,4 glycogen chain) n + Pi ⇌ (α-1,4 glycogen chain) n-1 + α-D-glucose-1-phosphate. [ 2 ]
Glycogen is left with one fewer glucose molecule , and the free glucose molecule is in the form of glucose-1-phosphate . In order to be used for metabolism , it must be converted to glucose-6-phosphate by the enzyme phosphoglucomutase .
Although the reaction is reversible in vitro , within the cell the enzyme only works in the forward direction as shown below because the concentration of inorganic phosphate is much higher than that of glucose-1-phosphate. [ 2 ]
Glycogen phosphorylase can act only on linear chains of glycogen (α1-4 glycosidic linkage). Its work will immediately come to a halt four residues away from α1-6 branch (which are exceedingly common in glycogen). In these situations, the debranching enzyme is necessary, which will straighten out the chain in that area. In addition, the enzyme transferase shifts a block of 3 glucosyl residues from the outer branch to the other end, and then a α1-6 glucosidase enzyme is required to break the remaining (single glucose) α1-6 residue that remains in the new linear chain. After all this is done, glycogen phosphorylase can continue. The enzyme is specific to α1-4 chains, as the molecule contains a 30-angstrom-long crevice with the same radius as the helix formed by the glycogen chain; this accommodates 4-5 glucosyl residues, but is too narrow for branches. This crevice connects the glycogen storage site to the active, catalytic site.
Glycogen phosphorylase has a pyridoxal phosphate (PLP, derived from Vitamin B 6 ) at each catalytic site. Pyridoxal phosphate links with basic residues (in this case Lys680) and covalently forms a Schiff base . Once the Schiff base linkage is formed, holding the PLP molecule in the active site, the phosphate group on the PLP readily donates a proton to an inorganic phosphate molecule, allowing the inorganic phosphate to in turn be deprotonated by the oxygen forming the α-1,4 glycosidic linkage. PLP is readily deprotonated because its negative charge is not only stabilized within the phosphate group, but also in the pyridine ring, thus the conjugate base resulting from the deprotonation of PLP is quite stable. The protonated oxygen now represents a good leaving group , and the glycogen chain is separated from the terminal glycogen in an S N 1 fashion, resulting in the formation of a glucose molecule with a secondary carbocation at the 1 position. Finally, the deprotonated inorganic phosphate acts as a nucleophile and bonds with the carbocation, resulting in the formation of glucose-1-phosphate and a glycogen chain shortened by one glucose molecule.
There is also an alternative proposed mechanism involving a positively charged oxygen in a half-chair conformation. [ 3 ]
The glycogen phosphorylase monomer is a large protein, composed of 842 amino acids with a mass of 97.434 kDa in muscle cells. While the enzyme can exist as an inactive monomer or tetramer, it is biologically active as a dimer of two identical subunits. [ 4 ]
In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver, and brain. The brain type is predominant in adult brain and embryonic tissues, whereas the liver and muscle types are predominant in adult liver and skeletal muscle, respectively. [ 5 ]
The glycogen phosphorylase dimer has many regions of biological significance, including catalytic sites, glycogen binding sites, allosteric sites, and a reversibly phosphorylated serine residue. First, the catalytic sites are relatively buried, 15Å from the surface of the protein and from the subunit interface. [ 6 ] This lack of easy access of the catalytic site to the surface is significant in that it makes the protein activity highly susceptible to regulation, as small allosteric effects could greatly increase the relative access of glycogen to the site.
Perhaps the most important regulatory site is Ser14, the site of reversible phosphorylation very close to the subunit interface. The structural change associated with phosphorylation, and with the conversion of phosphorylase b to phosphorylase a, is the arrangement of the originally disordered residues 10 to 22 into α helices. This change increases phosphorylase activity up to 25% even in the absence of AMP, and enhances AMP activation further. [ 7 ]
The allosteric site of AMP binding on muscle isoforms of glycogen phosphorylase are close to the subunit interface just like Ser14. Binding of AMP at this site, corresponding in a change from the T state of the enzyme to the R state, results in small changes in tertiary structure at the subunit interface leading to large changes in quaternary structure. [ 8 ] AMP binding rotates the tower helices (residues 262-278) of the two subunits 50˚ relative to one another through greater organization and intersubunit interactions. This rotation of the tower helices leads to a rotation of the two subunits by 10˚ relative to one another, and more importantly disorders residues 282-286 (the 280s loop) that block access to the catalytic site in the T state but do not in the R state. [ 6 ]
The final, perhaps most curious site on the glycogen phosphorylase protein is the so-called glycogen storage site. Residues 397-437 form this structure, which allows the protein to covalently bind to the glycogen chain a full 30 Å from the catalytic site . This site is most likely the site at which the enzyme binds to glycogen granules before initiating cleavage of terminal glucose molecules. In fact, 70% of dimeric phosphorylase in the cell exists as bound to glycogen granules rather than free floating. [ 9 ]
The inhibition of glycogen phosphorylase has been proposed as one method for treating type 2 diabetes . [ 10 ] Since glucose production in the liver has been shown to increase in type 2 diabetes patients, [ 11 ] inhibiting the release of glucose from the liver's glycogen's supplies appears to be a valid approach. The cloning of the human liver glycogen phosphorylase (HLGP) revealed a new allosteric binding site near the subunit interface that is not present in the rabbit muscle glycogen phosphorylase (RMGP) normally used in studies. This site was not sensitive to the same inhibitors as those at the AMP allosteric site, [ 12 ] and most success has been had synthesizing new inhibitors that mimic the structure of glucose, since glucose-6-phosphate is a known inhibitor of HLGP and stabilizes the less active T-state. [ 13 ] These glucose derivatives have had some success in inhibiting HLGP, with predicted Ki values as low as 0.016 mM. [ 14 ]
Mutations in the muscle isoform of glycogen phosphorylase (PYGM) are associated with glycogen storage disease type V (GSD V, McArdle's Disease). More than 65 mutations in the PYGM gene that lead to McArdle disease have been identified to date. [ 15 ] [ 16 ] Symptoms of McArdle disease include muscle weakness, myalgia , and lack of endurance, all stemming from low glucose levels in muscle tissue. [ 17 ]
Mutations in the liver isoform of glycogen phosphorylase (PYGL) are associated with Hers' Disease ( glycogen storage disease type VI ). [ 18 ] [ 19 ] Hers' disease is often associated with mild symptoms normally limited to hypoglycemia , and is sometimes difficult to diagnose due to residual enzyme activity. [ 20 ]
The brain isoform of glycogen phosphorylase (PYGB) has been proposed as a biomarker for gastric cancer . [ 21 ]
Glycogen phosphorylase is regulated through allosteric control and through phosphorylation . Phosphorylase a and phosphorylase b each exist in two forms: a T (tense) inactive state and an R (relaxed) state. Phosphorylase b is normally in the T state, inactive due to the physiological presence of ATP and glucose 6 phosphate, and phosphorylase a is normally in the R state (active). An isoenzyme of glycogen phosphorylase exists in the liver sensitive to glucose concentration, as the liver acts as a glucose exporter. In essence, liver phosphorylase is responsive to glucose, which causes a very responsive transition from the R to T form, inactivating it; furthermore, liver phosphorylase is insensitive to AMP.
Hormones such as epinephrine , insulin and glucagon regulate glycogen phosphorylase using second messenger amplification systems linked to G proteins . Glucagon activates adenylate cyclase through a G protein-coupled receptor (GPCR) coupled to G s which in turn activates adenylate cyclase to increase intracellular concentrations of cAMP. cAMP binds to and activates protein kinase A (PKA). PKA phosphorylates phosphorylase kinase , which in turn phosphorylates glycogen phosphorylase b at Ser14, converting it into the active glycogen phosphorylase a.
In the liver, glucagon also activates another GPCR that triggers a different cascade, resulting in the activation of phospholipase C (PLC). PLC indirectly causes the release of calcium from the hepatocytes' endoplasmic reticulum into the cytosol. The increased calcium availability binds to the calmodulin subunit and activates glycogen phosphorylase kinase. Glycogen phosphorylase kinase activates glycogen phosphorylase in the same manner mentioned previously.
Glycogen phosphorylase b is not always inactive in muscle, as it can be activated allosterically by AMP. [ 6 ] [ 9 ] An increase in AMP concentration, which occurs during strenuous exercise, signals energy demand. AMP activates glycogen phosphorylase b by changing its conformation from a tense to a relaxed form. This relaxed form has similar enzymatic properties as the phosphorylated enzyme. An increase in ATP concentration opposes this activation by displacing AMP from the nucleotide binding site, indicating sufficient energy stores.
Upon eating a meal, there is a release of insulin , signaling glucose availability in the blood. Insulin indirectly activates protein phosphatase 1 (PP1) and phosphodiesterase via a signal transduction cascade. PP1 dephosphorylates glycogen phosphorylase a, reforming the inactive glycogen phosphorylase b. The phosphodiesterase converts cAMP to AMP. Together, they decrease the concentration of cAMP and inhibit PKA. As a result, PKA can no longer initiate the phosphorylation cascade that ends with formation of (active) glycogen phosphorylase a. Overall, insulin signaling decreases glycogenolysis to preserve glycogen stores in the cell and triggers glycogenesis . [ 22 ]
Glycogen phosphorylase was the first allosteric enzyme to be discovered. [ 8 ] It was isolated and its activity characterized in detail by Carl F. Cori , Gerhard Schmidt and Gerty T. Cori . [ 23 ] [ 24 ] Arda Green and Gerty Cori crystallized it for the first time in 1943 [ 25 ] and illustrated that glycogen phosphorylase existed in either the a or b forms depending on its phosphorylation state, as well as in the R or T states based on the presence of AMP. [ 26 ] | https://en.wikipedia.org/wiki/Glycogen_phosphorylase |
Glycogen synthase ( UDP-glucose-glycogen glucosyltransferase ) is a key enzyme in glycogenesis , the conversion of glucose into glycogen . It is a glycosyltransferase ( EC 2.4.1.11 ) that catalyses the reaction of UDP-glucose and (1,4- α - D -glucosyl) n to yield UDP and (1,4- α - D -glucosyl) n+1 .
Much research has been done on glycogen degradation through studying the structure and function of glycogen phosphorylase , the key regulatory enzyme of glycogen degradation. [ 1 ] On the other hand, much less is known about the structure of glycogen synthase, the key regulatory enzyme of glycogen synthesis. The crystal structure of glycogen synthase from Agrobacterium tumefaciens , however, has been determined at 2.3 A resolution. [ 2 ] In its asymmetric form, glycogen synthase is found as a dimer, whose monomers are composed of two Rossmann-fold domains. This structural property, among others, is shared with related enzymes, such as glycogen phosphorylase and other glycosyltransferases of the GT-B superfamily. [ 3 ] Nonetheless, a more recent characterization of the Saccharomyces cerevisiae (yeast) glycogen synthase crystal structure reveals that the dimers may actually interact to form a tetramer . Specifically, The inter-subunit interactions are mediated by the α15/16 helix pairs, forming allosteric sites between subunits in one combination of dimers and active sites between subunits in the other combination of dimers. Since the structure of eukaryotic glycogen synthase is highly conserved among species, glycogen synthase likely forms a tetramer in humans as well. [ 4 ]
Glycogen synthase can be classified in two general protein families. The first family (GT3), which is from mammals and yeast, is approximately 80 kDa, uses UDP-glucose as a sugar donor, and is regulated by phosphorylation and ligand binding. [ 5 ] The second family (GT5), which is from bacteria and plants, is approximately 50 kDA, uses ADP-glucose as a sugar donor, and is unregulated. [ 6 ]
Although the catalytic mechanisms used by glycogen synthase are not well known, structural similarities to glycogen phosphorylase at the catalytic and substrate binding site suggest that the mechanism for synthesis is similar in glycogen synthase and glycogen phosphorylase. [ 2 ]
Glycogen synthase catalyzes the conversion of the glucosyl (Glc) moiety of uridine diphosphate glucose (UDP-Glc) into glucose to be incorporated into glycogen via an α(1→4) glycosidic bond . However, since glycogen synthase requires an oligosaccharide primer as a glucose acceptor, it relies on glycogenin to initiate de novo glycogen synthesis. [ 4 ]
In a recent study of transgenic mice, an overexpression of glycogen synthase [ 7 ] and an overexpression of phosphatase [ 8 ] both resulted in excess glycogen storage levels. This suggests that glycogen synthase plays an important biological role in regulating glycogen/glucose levels and is activated by dephosphorylation.
In humans, there are two paralogous isozymes of glycogen synthase:
The liver enzyme expression is restricted to the liver, whereas the muscle enzyme is widely expressed. Liver glycogen serves as a storage pool to maintain the blood glucose level during fasting, whereas muscle glycogen synthesis accounts for disposal of up to 90% of ingested glucose. The role of muscle glycogen is as a reserve to provide energy during bursts of activity. [ 11 ]
Meanwhile, the muscle isozyme plays a major role in the cellular response to long-term adaptation to hypoxia . Notably, hypoxia only induces expression of the muscle isozyme and not the liver isozyme. However, muscle-specific glycogen synthase activation may lead to excessive accumulation of glycogen, leading to damage in the heart and central nervous system following ischemic insults. [ 12 ]
The reaction is highly regulated by allosteric effectors such as glucose 6-phosphate (activator) and by phosphorylation reactions (deactivating). Glucose-6-phosphate allosteric activating action allows glycogen synthase to operate as a glucose-6-phosphate sensor. The inactivating phosphorylation is triggered by the hormone glucagon , which is secreted by the pancreas in response to decreased blood glucose levels. The enzyme also cleaves the ester bond between the C1 position of glucose and the pyrophosphate of UDP itself.
The control of glycogen synthase is a key step in regulating glycogen metabolism and glucose storage. Glycogen synthase is directly regulated by glycogen synthase kinase 3 (GSK-3), AMPK , protein kinase A (PKA), and casein kinase 2 (CK2). Each of these protein kinases leads to phosphorylated and catalytically inactive glycogen synthase. The phosphorylation sites of glycogen synthase are summarized below.
For enzymes in the GT3 family, these regulatory kinases inactivate glycogen synthase by phosphorylating it at the N-terminal of the 25th residue and the C-terminal of the 120th residue. [ 2 ] Glycogen synthase is also regulated by protein phosphatase 1 ( PP1 ), which activates glycogen synthase via dephosphorylation. [ 18 ] PP1 is targeted to the glycogen pellet by four targeting subunits, G M , G L , PTG and R6 . These regulatory enzymes are regulated by insulin and glucagon signaling pathways.
Mutations in the GYS1 gene are associated with glycogen storage disease type 0 . [ 19 ] In humans, defects in the tight control of glucose uptake and utilization are also associated with diabetes and hyperglycemia . Patients with type 2 diabetes normally exhibit low glycogen storage levels because of impairments in insulin-stimulated glycogen synthesis and suppression of glycogenolysis. Insulin stimulates glycogen synthase by inhibiting glycogen synthase kinases or/and activating protein phosphatase 1 (PP1) among other mechanisms. [ 18 ] | https://en.wikipedia.org/wiki/Glycogen_synthase |
Glycogenesis is the process of glycogen synthesis or the process of converting glucose into glycogen in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle , in the liver , and also activated by insulin in response to high glucose levels . [ 1 ]
Glycogenesis responds to hormonal control.
One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase. This is regulated by enzymes under the control of hormonal activity, which is in turn regulated by many factors. As such, there are many different possible effectors when compared to allosteric systems of regulation.
Glycogen phosphorylase is activated by phosphorylation, whereas glycogen synthase is inhibited.
Glycogen phosphorylase is converted from its less active "b" form to an active "a" form by the enzyme phosphorylase kinase. This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1.
Protein kinase A itself is activated by the hormone adrenaline. Epinephrine binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP from ATP ; two molecules of cyclic AMP bind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic subunit of protein kinase A to dissociate from the assembly and to phosphorylate other proteins.
Returning to glycogen phosphorylase, the less active "b" form can itself be activated without the conformational change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor, as already seen with phosphofructokinase control, helping to change the rate of flux in response to energy demand.
Epinephrine not only activates glycogen phosphorylase but also inhibits glycogen synthase. This amplifies the effect of activating glycogen phosphorylase. This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity. This is known as co-ordinate reciprocal control. Refer to glycolysis for further information of the regulation of glycogenesis.
Calcium ions or cyclic AMP (cAMP) act as secondary messengers. This is an example of negative control. The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase. | https://en.wikipedia.org/wiki/Glycogenesis |
Glycogenin is an enzyme involved in converting glucose to glycogen . It acts as a primer , by polymerizing the first few glucose molecules, after which other enzymes take over. It is a homodimer of 37- kDa subunits and is classified as a glycosyltransferase .
It catalyzes the chemical reactions :
Thus, the two substrates of this enzyme are UDP-alpha-D-glucose and glycogenin , whereas its two products are UDP and alpha-D-glucosylglycogenin . [ 2 ] [ 3 ]
This enzyme belongs to the family of glycosyltransferases , specifically the hexosyltransferases. The systematic name of this enzyme class is UDP-alpha-D-glucose:glycogenin alpha-D-glucosyltransferase . Other names in common use include:
One may also notice that the naming of glycogenin hints at its function, with the glyco prefix referring to a carbohydrate and the genin suffix derived from the Latin genesis meaning novel, source, or beginning. This hints at the role of glycogenin to simply start glycogen synthesis before glycogen synthase takes over.
Glycogenin was discovered in 1984 by Dr. William J. Whelan , a fellow of the Royal Society of London and former professor of Biochemistry at the University of Miami . [ 4 ]
The main enzyme involved in glycogen polymerisation , glycogen synthase in the liver and in the muscle glycogen synthesis is initiated by UDP-Glucose, can only add to an existing chain of at least 3 glucose residues. Glycogenin acts as the primer , to which further glucose monomers may be added. It achieves this by catalyzing the addition of glucose to itself ( autocatalysis ) by first binding glucose from UDP-glucose to the hydroxyl group of Tyr-194. Seven more glucoses can be added, each derived from UDP-glucose, by glycogenin's glucosyltransferase activity. Once sufficient residues have been added, glycogen synthase takes over extending the chain. Glycogenin remains covalently attached to the reducing end of the glycogen molecule .
Evidence accumulates that a priming protein may be a fundamental property of polysaccharide synthesis in general; the molecular details of mammalian glycogen biogenesis may serve as a useful model for other systems.
Glycogenin is able to use the other two pyrimidine nucleotides as well, namely CDP-glucose and TDP-glucose , in addition to its native substrate, UDP-glucose. [ 5 ]
In humans, there are two isoforms of glycogenin — glycogenin-1, encoded by GYG1, and expressed in muscle; and glycogenin-2, encoded by GYG2, and expressed in the liver and cardiac muscle, but not skeletal muscle. Patients have been found with defective GYG1, resulting in muscle cells with the inability to store glycogen, and consequential weakness and heart disease. [ 7 ] | https://en.wikipedia.org/wiki/Glycogenin |
3Q4S , 3QVB , 3RMV , 3RMW , 3T7M , 3T7N , 3T7O , 3U2T , 3U2U , 3U2V , 3U2W , 3U2X
2992
27357
ENSG00000163754
ENSMUSG00000019528
P46976
Q9R062
NM_004130 NM_001184720 NM_001184721
NM_013755 NM_001355261
NP_001171649 NP_001171650 NP_004121
NP_038783 NP_001342190
Glycogenin-1 is an enzyme that is involved in the biosynthesis of glycogen . It is capable of self-glucosylation, forming an oligosaccharide primer that serves as a substrate for glycogen synthase. This is done through an inter-subunit mechanism. It also plays a role in glycogen metabolism regulation. Recombinant human glycogenin-1 was expressed in E. coli and purified using conventional chromatography techniques. [ 5 ]
Glycogen is a multi-branched polysaccharide . It is primary means of glucose storage in animal cells. In the human body, the two main tissues which store glycogen are liver and skeletal muscle. [ 6 ] Glycogen is typically more concentrated in the liver, but because humans have much more muscle mass, our muscles store about three quarters of the total glycogen in our body.
The function of liver glycogen is to maintain glucose homeostasis, generating glucose via glycogenolysis to compensate for the decrease of glucose levels that can occur between meals. Thanks to the presence of the glucose-6-phosphatase enzyme, the hepatocytes are capable of turning glycogen to glucose, releasing it into blood to prevent hypoglycemia .
In skeletal muscle, glycogen is used as an energy source for muscle contraction during exercise. The different functions of glycogen in muscle or liver make the regulation mechanisms of its metabolism differ in each tissue. [ 7 ] These mechanisms are based mainly on the differences on structure and on the regulation of the enzymes that catalyze synthesis, glycogen synthase (GS), and degradation, glycogen phosphorylase (GF).
Glycogenin is the initiator of the glycogen biosynthesis. [ 8 ] [ 9 ] This protein is a glycosyl transferase that have the ability of autoglycosilation using UDP-glucose, [ 10 ] which helps in the growth of itself until forming an oligosaccharide made by 8 glucoses. Glycogenin is an oligomer , and it's capable of interacting with several proteins. In recent years, a family of proteins has been identified, the GNIPs (glycogenin-interacting protein), that interacts with glycogenin stimulating its autoglycolsilation activity.
In humans, two isoforms of glycogenin can be expressed: glycogenin-1, with a molecular weight of 37 kDa and codified by GYG1 gen, which is expressed mostly in muscles; and glycogenin-2, with a molecular weight of 66 kDa and codified by GYG2 gen, which is expressed mainly in liver, cardiac muscle and other types of tissue, but not in skeletal muscle. [ 11 ] Glycogenin-1 was described by analyzing the glycogen of skeletal muscle. It was determined that this molecule was united by a covalent bond to each mature molecule of muscular glycogen. [ 12 ]
The glycogenin-1 gene, which spans over 13kb, consists of seven exons and six introns . Its proximal promoter contains a TATA box , a cyclic AMP responsive element, and two putative Sp1 binding sites in a CpG island , a DNA region with a high frequency of CpG sites . There are also nine E-boxes that bind the basic helix-loop-helix of muscle-specific transcription factors. [ 13 ]
The GYG1 gene is located on the long arm of the chromosome 3 , between positions 24 and 25, from base pair 148,709,194 to base pair 148,745,455. [ 14 ]
Transcription of human glycogenin-1 is mainly initiated at 80bp and 86bp upstream the translator’s codon beginning. Transcriptions factors have different binding sites for its development, some examples are: GATA, activator protein 1 and 2 (AP-1 and AP-2), and numerous potential Octamer-1 binding sites. [ 15 ]
A Glycogenin-1 deficiency leads to Glycogen storage disease type XV .
Deficiency of glycogenin-1 is detected in the sequence of the glycogenin-1 gene, GYG1, which revealed a non-sense mutation in one allele and a missense mutation , Thr83Met, in the other. The missense mutation resulted in inactivation of the autoglycosylation of glycogenin-1, which is necessary for the priming of glycogen synthesis in muscle.
Autoglycosylation of glycogenin-1 occurs at Tyr195 by a gulose-1-O-tyrosine linkage. An induced missense mutation of this residue results in inactivated autoglycosylation. However, missense mutation affecting some other residues of glycogenin-1 has also been shown to eliminate autoglycosilation.
The phenotypic features of the skeletal muscle in a patient with this disorder are muscle glycogen depletion, mitochondrial proliferation, and a marked predominance of slow-twitch, oxidative muscle fibres. The mutations in the glycogenin-1 gene GYG1 are also a cause of cardiomyopathy and arrhythmia . [ 11 ] | https://en.wikipedia.org/wiki/Glycogenin-1 |
Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis , by the enzyme glycogen phosphorylase . [ 1 ]
In the muscles, glycogenolysis begins due to the binding of cAMP to phosphorylate kinase , converting the latter to its active form so it can convert phosphorylase b to phosphorylase a , which is responsible for catalyzing the breakdown of glycogen. [ 2 ]
The overall reaction for the breakdown of glycogen to glucose-1-phosphate is: [ 1 ]
Here, glycogen phosphorylase cleaves the bond linking a terminal glucose residue to a glycogen branch by substitution of a phosphoryl group for the α[1→4] linkage. [ 1 ]
Glucose-1-phosphate is converted to glucose-6-phosphate (which often ends up in glycolysis ) by the enzyme phosphoglucomutase . [ 1 ]
Glucose residues are phosphorolysed from branches of glycogen until four residues before a glucose that is branched with a α[1→6] linkage. Glycogen debranching enzyme then transfers three of the remaining four glucose units to the end of another glycogen branch. This exposes the α[1→6] branching point, which is hydrolysed by α[1→6] glucosidase , removing the final glucose residue of the branch as a molecule of glucose and eliminating the branch. This is the only case in which a glycogen metabolite is not glucose-1-phosphate. The glucose is subsequently phosphorylated to glucose-6-phosphate by hexokinase . [ 1 ]
Glycogenolysis takes place in the cells of the muscle and liver tissues in response to hormonal and neural signals. In particular, glycogenolysis plays an important role in the fight-or-flight response and the regulation of glucose levels in the blood.
In myocytes (muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for glycolysis , to provide energy for muscle contraction. Glucose-6-phosphate can not pass through the cell membrane, and is therefore used solely by the myocytes that produce it.
In hepatocytes (liver cells), the main purpose of the breakdown of glycogen is for the release of glucose into the bloodstream for uptake by other cells. The phosphate group of glucose-6-phosphate is removed by the enzyme glucose-6-phosphatase , which is not present in myocytes, and the free glucose exits the cell via GLUT2 facilitated diffusion channels in the hepatocyte cell membrane.
Glycogenolysis is regulated hormonally in response to blood sugar levels by glucagon and insulin , and stimulated by epinephrine during the fight-or-flight response . Insulin potently inhibits glycogenolysis. [ 4 ]
In myocytes, glycogen degradation may also be stimulated by neural signals; [ 5 ] glycogenolysis is regulated by epinephrine and calcium released by the sarcoplasmic reticulum . [ 3 ]
Glucagon has no effect on muscle glycogenolysis. [ 3 ]
Calcium binds with calmodulin and the complex activates phosphorylase kinase. [ 3 ]
Parenteral ( intravenous ) administration of glucagon is a common human medical intervention in diabetic emergencies when sugar cannot be given orally. It can also be administered intramuscularly . | https://en.wikipedia.org/wiki/Glycogenolysis |
Glycoinformatics is a field of bioinformatics that pertains to the study of carbohydrates involved in protein post-translational modification . It broadly includes (but is not restricted to) database , software , and algorithm development for the study of carbohydrate structures , glycoconjugates , enzymatic carbohydrate synthesis and degradation , as well as carbohydrate interactions . Conventional usage of the term does not currently include the treatment of carbohydrates from the better-known nutritive aspect.
Even though glycosylation is the most common form of protein modification, with highly complex carbohydrate structures, the bioinformatics on glycome is still very poor. [ 2 ] [ 3 ]
Unlike proteins and nucleic acids which are linear, carbohydrates are often branched and extremely complex. [ 4 ] For instance, just four sugars can be strung together to form more than 5 million different types of carbohydrates [ 5 ] or nine different sugars may be assembled into 15 million possible four-sugar-chains. [ 6 ]
Also, the number of simple sugars that make up glycans is more than the number of nucleotides that make up DNA or RNA. Therefore, it is more computationally expensive to evaluate their structures. [ 7 ]
One of the main constrains in the glycoinformatics is the difficulty of representing sugars in the sequence form especially due to their branching nature. [ 6 ] Owing to the lack of a genetic blue print, carbohydrates do not have a "fixed" sequence. Instead, the sequence is largely determined by the presence of a variety of enzymes, their kinetic differences and variations in the biosynthetic micro-environment of the cells. This increases the complexity of analysis and experimental reproducibility of the carbohydrate structure of interest. [ 8 ] It is for this reason that carbohydrates are often considered as the "information poor" molecules.
Table of major glyco-databases. [ 9 ] [ 10 ] | https://en.wikipedia.org/wiki/Glycoinformatics |
Glycol dehydration is a liquid desiccant system for the removal of water from natural gas and natural gas liquids (NGL). It is the most common and economical means of water removal from these streams. [ 1 ] Glycols typically seen in industry include triethylene glycol (TEG), diethylene glycol (DEG), ethylene glycol (MEG), and tetraethylene glycol (TREG). TEG is the most commonly used glycol in industry. [ 1 ]
The purpose of a glycol dehydration unit is to remove water from natural gas and natural gas liquids. When produced from a reservoir , natural gas usually contains a large amount of water and is typically completely saturated or at the water dew point . This water can cause several problems for downstream processes and equipment. At low temperatures the water can either freeze in piping or, as is more commonly the case, form hydrates with CO 2 and hydrocarbons (mainly methane hydrates). Depending on composition, these hydrates can form at relatively high temperatures plugging equipment and piping. [ 1 ] Glycol dehydration units depress the hydrate formation point of the gas through water removal.
Without dehydration, a free water phase (liquid water) could also drop out of the natural gas as it is either cooled or the pressure is lowered through equipment and piping. This free water phase will often contain some portions of acid gas (such as H 2 S and CO 2 ) and can cause corrosion . [ 1 ]
For the above two reasons the Gas Processors Association sets out a pipeline quality specification for gas that the water content should not exceed 7 pounds per million standard cubic feet . [ 1 ] Glycol dehydration units must typically meet this specification at a minimum, although further removal may be required if additional hydrate formation temperature depression is required, such as upstream of a cryogenic process or gas plant .
Lean, water-free glycol (purity >99%) is fed to the top of an absorber (also known as a "glycol contactor") where it is contacted with the wet natural gas stream. The glycol removes water from the natural gas by physical absorption and is carried out the bottom of the column. Upon exiting the absorber the glycol stream is often referred to as "rich glycol". The dry natural gas leaves the top of the absorption column and is fed either to a pipeline system or to a gas plant. Glycol absorbers can be either tray columns or packed columns.
After leaving the absorber, the rich glycol is fed to a flash vessel where hydrocarbon vapors are removed and any liquid hydrocarbons are skimmed from the glycol. This step is necessary as the absorber is typically operated at high pressure and the pressure must be reduced before the regeneration step. Due to the composition of the rich glycol, a vapor phase having a high hydrocarbon content will form when the pressure is lowered.
After leaving the flash vessel, the rich glycol is heated in a cross-exchanger and fed to the stripper (also known as a regenerator). The glycol stripper consists of a column, an overhead condenser, and a reboiler. The glycol is thermally regenerated to remove excess water and regain the high glycol purity. The rich Glycols are used in heat transfers and cooling. It provides better heat transfer parameters. With water they can provide a variety of heat transfer characteristics, it also prevents the water from freezing at low temperatures within the piping system. furthermore looking at other general uses, glycol is a chemical commonly used in many commercial and industrial applications including antifreeze and coolant. Ethylene glycol helps keep your car's engine from freezing in the winter and acts as a coolant to reduce overheating in the summer
The hot, lean glycol is cooled by cross-exchange with rich glycol entering the stripper. It is then fed to a lean pump where its pressure is elevated to that of the glycol absorber. The lean solvent is cooled again with a trim cooler before being fed back into the absorber. This trim cooler can either be a cross-exchanger with the dry gas leaving the absorber or an air-cooled exchanger. [ 2 ]
Most glycol units are fairly uniform except for the regeneration step. Several methods are used to enhance the stripping of the glycol to higher purities (higher purities are required for dryer gas out of the absorber). Since the reboiler temperature is limited to 400F or less to prevent thermal degradation of the glycol, almost all of the enhanced systems center on lowering the partial pressure of water in the system to increase stripping.
Common enhanced methods include the use of stripping gas, the use of a vacuum system (lowering the entire stripper pressure), the DRIZO process, which is similar to the use of stripping gas but uses a recoverable hydrocarbon solvent, and the Coldfinger process where the vapors in the reboiler are partially condensed and drawn out separately from the bulk liquid. | https://en.wikipedia.org/wiki/Glycol_dehydration |
Glycolipids ( / ˈ ɡ l aɪ k oʊ ˌ l ɪ p ɪ d z / ) are lipids with a carbohydrate attached by a glycosidic (covalent) bond . [ 1 ] Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues . [ 2 ] Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment. [ 2 ]
The essential feature of a glycolipid is the presence of a monosaccharide or oligosaccharide bound to a lipid moiety . The most common lipids in cellular membranes are glycerolipids and sphingolipids , which have glycerol or a sphingosine backbones, respectively. Fatty acids are connected to this backbone, so that the lipid as a whole has a polar head and a non-polar tail. The lipid bilayer of the cell membrane consists of two layers of lipids, with the inner and outer surfaces of the membrane made up of the polar head groups, and the inner part of the membrane made up of the non-polar fatty acid tails.
The saccharides that are attached to the polar head groups on the outside of the cell are the ligand components of glycolipids, and are likewise polar, allowing them to be soluble in the aqueous environment surrounding the cell. [ 3 ] The lipid and the saccharide form a glycoconjugate through a glycosidic bond , which is a covalent bond . The anomeric carbon of the sugar binds to a free hydroxyl group on the lipid backbone. The structure of these saccharides varies depending on the structure of the molecules to which they bind.
Enzymes called glycosyltransferases link the saccharide to the lipid molecule, and also play a role in assembling the correct oligosaccharide so that the right receptor can be activated on the cell which responds to the presence of the glycolipid on the surface of the cell. The glycolipid is assembled in the Golgi apparatus and embedded in the surface of a vesicle which is then transported to the cell membrane. The vesicle merges with the cell membrane so that the glycolipid can be presented on the cell's outside surface. [ 4 ]
Glycoside hydrolases catalyze the breakage of glycosidic bonds. They are used to modify the oligosaccharide structure of the glycan after it has been added onto the lipid. They can also remove glycans from glycolipids to turn them back into unmodified lipids. [ 5 ]
Sphingolipidoses are a group of diseases that are associated with the accumulation of sphingolipids which have not been degraded correctly, normally due to a defect in a glycoside hydrolase enzyme. Sphingolipidoses are typically inherited, and their effects depend on which enzyme is affected, and the degree of impairment. One notable example is Niemann–Pick disease which can cause pain and damage to neural networks. [ 6 ]
The main function of glycolipids in the body is to serve as recognition sites for cell–cell interactions. The saccharide of the glycolipid will bind to a specific complementary carbohydrate or to a lectin (carbohydrate-binding protein), of a neighboring cell. The interaction of these cell surface markers is the basis of cell recognitions, and initiates cellular responses that contribute to activities such as regulation, growth, and apoptosis . [ 7 ]
An example of how glycolipids function within the body is the interaction between leukocytes and endothelial cells during inflammation. Selectins , a class of lectins found on the surface of leukocytes and endothelial cells bind to the carbohydrates attached to glycolipids to initiate the immune response. This binding causes leukocytes to leave circulation and congregate near the site of inflammation. This is the initial binding mechanism, which is followed by the expression of integrins which form stronger bonds and allow leukocytes to migrate toward the site of inflammation. [ 8 ] Glycolipids are also responsible for other responses, notably the recognition of host cells by viruses. [ 9 ]
Blood types are an example of how glycolipids on cell membranes mediate cell interactions with the surrounding environment. The four main human blood types (A, B, AB, O) are determined by the oligosaccharide attached to a specific glycolipid on the surface of red blood cells , which acts as an antigen . The unmodified antigen, called the H antigen, is the characteristic of type O, and is present on red blood cells of all blood types. Blood type A has an N-acetylgalactosamine added as the main determining structure, type B has a galactose , and type AB has all three of these antigens. Antigens which are not present in an individual's blood will cause antibodies to be produced, which will bind to the foreign glycolipids. For this reason, people with blood type AB can receive transfusions from all blood types (the universal acceptor), and people with blood type O can act as donors to all blood types (the universal donor). [ 10 ] | https://en.wikipedia.org/wiki/Glycolipid |
Glycolysis is the metabolic pathway that converts glucose ( C 6 H 12 O 6 ) into pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol ). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). [ 1 ] Glycolysis is a sequence of ten reactions catalyzed by enzymes .
The wide occurrence of glycolysis in other species indicates that it is an ancient metabolic pathway. [ 2 ] Indeed, the reactions that make up glycolysis and its parallel pathway, the pentose phosphate pathway , can occur in the oxygen-free conditions of the Archean oceans, also in the absence of enzymes, catalyzed by metal ions, meaning this is a plausible prebiotic pathway for abiogenesis . [ 3 ]
The most common type of glycolysis is the Embden–Meyerhof–Parnas (EMP) pathway , which was discovered by Gustav Embden , Otto Meyerhof , and Jakub Karol Parnas . Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. [ 4 ]
The glycolysis pathway can be separated into two phases: [ 5 ]
The overall reaction of glycolysis is:
d -Glucose
2 × Pyruvate
The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. Atom balance is maintained by the two phosphate (P i ) groups: [ 6 ]
Charges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxyl groups of ADP dissociate into −O − and H + , giving ADP 3− , and this ion tends to exist in an ionic bond with Mg 2+ , giving ADPMg − . ATP behaves identically except that it has four hydroxyl groups, giving ATPMg 2− . When these differences along with the true charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. [ citation needed ]
In high-oxygen (aerobic) conditions, eukaryotic cells can continue from glycolysis to metabolise the pyruvate through the citric acid cycle or the electron transport chain to produce significantly more ATP.
Importantly, under low-oxygen (anaerobic) conditions, glycolysis is the only biochemical pathway in eukaryotes that can generate ATP, and, for many anaerobic respiring organisms the most important producer of ATP. [ 7 ] Therefore, many organisms have evolved fermentation pathways to recycle NAD + to continue glycolysis to produce ATP for survival. These pathways include ethanol fermentation and lactic acid fermentation .
The modern understanding of the pathway of glycolysis took almost 100 years to fully learn. [ 8 ] The combined results of many smaller experiments were required to understand the entire pathway.
The first steps in understanding glycolysis began in the 19th century. For economic reasons, the French wine industry sought to investigate why wine sometimes turned distasteful, instead of fermenting into alcohol. The French scientist Louis Pasteur researched this issue during the 1850s. [ 9 ] His experiments showed that alcohol fermentation occurs by the action of living microorganisms , yeasts, and that glucose consumption decreased under aerobic conditions (the Pasteur effect ). [ 10 ]
The component steps of glycolysis were first analysed by the non-cellular fermentation experiments of Eduard Buchner during the 1890s. [ 11 ] [ 12 ] Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast, due to the action of enzymes in the extract. [ 13 ] : 135–148 This experiment not only revolutionized biochemistry, but also allowed later scientists to analyze this pathway in a more controlled laboratory setting. In a series of experiments (1905–1911), scientists Arthur Harden and William Young discovered more pieces of glycolysis. [ 14 ] They discovered the regulatory effects of ATP on glucose consumption during alcohol fermentation. They also shed light on the role of one compound as a glycolysis intermediate: fructose 1,6-bisphosphate. [ 13 ] : 151–158
The elucidation of fructose 1,6-bisphosphate was accomplished by measuring CO 2 levels when yeast juice was incubated with glucose. CO 2 production increased rapidly then slowed down. Harden and Young noted that this process would restart if an inorganic phosphate (Pi) was added to the mixture. Harden and Young deduced that this process produced organic phosphate esters, and further experiments allowed them to extract fructose diphosphate (F-1,6-DP).
Arthur Harden and William Young along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction (the enzymes) and a heat-insensitive low-molecular-weight cytoplasm fraction (ADP, ATP and NAD + and other cofactors ) are required together for fermentation to proceed. This experiment begun by observing that dialyzed (purified) yeast juice could not ferment or even create a sugar phosphate. This mixture was rescued with the addition of undialyzed yeast extract that had been boiled. Boiling the yeast extract renders all proteins inactive (as it denatures them). The ability of boiled extract plus dialyzed juice to complete fermentation suggests that the cofactors were non-protein in character. [ 14 ]
In the 1920s Otto Meyerhof was able to link together some of the many individual pieces of glycolysis discovered by Buchner, Harden, and Young. Meyerhof and his team were able to extract different glycolytic enzymes from muscle tissue , and combine them to artificially create the pathway from glycogen to lactic acid. [ 15 ] [ 16 ]
In one paper, Meyerhof and scientist Renate Junowicz-Kockolaty investigated the reaction that splits fructose 1,6-diphosphate into the two triose phosphates. Previous work proposed that the split occurred via 1,3-diphosphoglyceraldehyde plus an oxidizing enzyme and cozymase. Meyerhoff and Junowicz found that the equilibrium constant for the isomerase and aldoses reaction were not affected by inorganic phosphates or any other cozymase or oxidizing enzymes. They further removed diphosphoglyceraldehyde as a possible intermediate in glycolysis. [ 16 ]
With all of these pieces available by the 1930s, Gustav Embden proposed a detailed, step-by-step outline of that pathway we now know as glycolysis. [ 17 ] The biggest difficulties in determining the intricacies of the pathway were due to the very short lifetime and low steady-state concentrations of the intermediates of the fast glycolytic reactions. By the 1940s, Meyerhof, Embden and many other biochemists had finally completed the puzzle of glycolysis. [ 16 ] The understanding of the isolated pathway has been expanded in the subsequent decades, to include further details of its regulation and integration with other metabolic pathways.
Glucose
Hexokinase
Glucose 6-phosphate
Glucose-6-phosphate isomerase
Fructose 6-phosphate
Phosphofructokinase-1
Fructose 1,6-bisphosphate
Fructose-bisphosphate aldolase
Dihydroxyacetone phosphate
+
Glyceraldehyde 3-phosphate
Triosephosphate isomerase
2 × Glyceraldehyde 3-phosphate
Glyceraldehyde-3-phosphate dehydrogenase
2 × 1,3-Bisphosphoglycerate
Phosphoglycerate kinase
2 × 3-Phosphoglycerate
Phosphoglycerate mutase
2 × 2-Phosphoglycerate
Phosphopyruvate hydratase ( enolase )
2 × Phosphoenolpyruvate
Pyruvate kinase
2 × Pyruvate
The first five steps of Glycolysis are regarded as the preparatory (or investment) phase, since they consume energy to convert the glucose into two three-carbon sugar phosphates [ 5 ] ( G3P ).
Once glucose enters the cell, the first step is phosphorylation of glucose by a family of enzymes called hexokinases to form glucose 6-phosphate (G6P). This reaction consumes ATP, but it acts to keep the glucose concentration inside the cell low, promoting continuous transport of blood glucose into the cell through the plasma membrane transporters. In addition, phosphorylation blocks the glucose from leaking out – the cell lacks transporters for G6P, and free diffusion out of the cell is prevented due to the charged nature of G6P. Glucose may alternatively be formed from the phosphorolysis or hydrolysis of intracellular starch or glycogen.
In animals , an isozyme of hexokinase called glucokinase is also used in the liver, which has a much lower affinity for glucose (K m in the vicinity of normal glycemia), and differs in regulatory properties. The different substrate affinity and alternate regulation of this enzyme are a reflection of the role of the liver in maintaining blood sugar levels.
Cofactors: Mg 2+
G6P is then rearranged into fructose 6-phosphate (F6P) by glucose phosphate isomerase . Fructose can also enter the glycolytic pathway by phosphorylation at this point.
The change in structure is an isomerization, in which the G6P has been converted to F6P. The reaction requires an enzyme, phosphoglucose isomerase, to proceed. This reaction is freely reversible under normal cell conditions. However, it is often driven forward because of a low concentration of F6P, which is constantly consumed during the next step of glycolysis. Under conditions of high F6P concentration, this reaction readily runs in reverse. This phenomenon can be explained through Le Chatelier's Principle . Isomerization to a keto sugar is necessary for carbanion stabilization in the fourth reaction step (below).
P i
The energy expenditure of another ATP in this step is justified in 2 ways: The glycolytic process (up to this step) becomes irreversible, and the energy supplied destabilizes the molecule. Because the reaction catalyzed by phosphofructokinase 1 (PFK-1) is coupled to the hydrolysis of ATP (an energetically favorable step) it is, in essence, irreversible, and a different pathway must be used to do the reverse conversion during gluconeogenesis . This makes the reaction a key regulatory point (see below).
Furthermore, the second phosphorylation event is necessary to allow the formation of two charged groups (rather than only one) in the subsequent step of glycolysis, ensuring the prevention of free diffusion of substrates out of the cell.
The same reaction can also be catalyzed by pyrophosphate-dependent phosphofructokinase ( PFP or PPi-PFK ), which is found in most plants, some bacteria, archea, and protists, but not in animals. This enzyme uses pyrophosphate (PPi) as a phosphate donor instead of ATP. It is a reversible reaction, increasing the flexibility of glycolytic metabolism. [ 18 ] A rarer ADP-dependent PFK enzyme variant has been identified in archaean species. [ 19 ]
Cofactors: Mg 2+
Destabilizing the molecule in the previous reaction allows the hexose ring to be split by aldolase into two triose sugars: dihydroxyacetone phosphate (a ketose), and glyceraldehyde 3-phosphate (an aldose). There are two classes of aldolases: class I aldolases, present in animals and plants, and class II aldolases, present in fungi and bacteria; the two classes use different mechanisms in cleaving the ketose ring.
Electrons delocalized in the carbon-carbon bond cleavage associate with the alcohol group. The resulting carbanion is stabilized by the structure of the carbanion itself via resonance charge distribution and by the presence of a charged ion prosthetic group.
Triosephosphate isomerase rapidly interconverts dihydroxyacetone phosphate with glyceraldehyde 3-phosphate ( GADP ) that proceeds further into glycolysis. This is advantageous, as it directs dihydroxyacetone phosphate down the same pathway as glyceraldehyde 3-phosphate, simplifying regulation.
The second half of glycolysis is known as the pay-off phase, characterised by a net gain of the energy-rich molecules ATP and NADH. [ 5 ] Since glucose leads to two triose sugars in the preparatory phase, each reaction in the pay-off phase occurs twice per glucose molecule. This yields 2 NADH molecules and 4 ATP molecules, leading to a net gain of 2 NADH molecules and 2 ATP molecules from the glycolytic pathway per glucose.
The aldehyde groups of the triose sugars are oxidised , and inorganic phosphate is added to them, forming 1,3-bisphosphoglycerate .
The hydrogen is used to reduce two molecules of NAD + , a hydrogen carrier, to give NADH + H + for each triose.
Hydrogen atom balance and charge balance are both maintained because the phosphate (P i ) group actually exists in the form of a hydrogen phosphate anion ( HPO 2− 4 ), [ 6 ] which dissociates to contribute the extra H + ion and gives a net charge of -3 on both sides.
Here, arsenate ( [AsO 4 ] 3− ), an anion akin to inorganic phosphate may replace phosphate as a substrate to form 1-arseno-3-phosphoglycerate. This, however, is unstable and readily hydrolyzes to form 3-phosphoglycerate , the intermediate in the next step of the pathway. As a consequence of bypassing this step, the molecule of ATP generated from 1-3 bisphosphoglycerate in the next reaction will not be made, even though the reaction proceeds. As a result, arsenate is an uncoupler of glycolysis. [ 20 ]
This step is the enzymatic transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP by phosphoglycerate kinase , forming ATP and 3-phosphoglycerate . At this step, glycolysis has reached the break-even point: 2 molecules of ATP were consumed, and 2 new molecules have now been synthesized. This step, one of the two substrate-level phosphorylation steps, requires ADP; thus, when the cell has plenty of ATP (and little ADP), this reaction does not occur. Because ATP decays relatively quickly when it is not metabolized, this is an important regulatory point in the glycolytic pathway.
ADP actually exists as ADPMg − , and ATP as ATPMg 2− , balancing the charges at −5 both sides.
Cofactors: Mg 2+
Phosphoglycerate mutase isomerises 3-phosphoglycerate into 2-phosphoglycerate .
Enolase next converts 2-phosphoglycerate to phosphoenolpyruvate . This reaction is an elimination reaction involving an E1cB mechanism.
Cofactors: 2 Mg 2+ , one "conformational" ion to coordinate with the carboxylate group of the substrate, and one "catalytic" ion that participates in the dehydration.
A final substrate-level phosphorylation now forms a molecule of pyruvate and a molecule of ATP by means of the enzyme pyruvate kinase . This serves as an additional regulatory step, similar to the phosphoglycerate kinase step.
Cofactors: Mg 2+
The existence of more than one point of regulation indicates that intermediates between those points enter and leave the glycolysis pathway by other processes. For example, in the first regulated step, hexokinase converts glucose into glucose-6-phosphate. Instead of continuing through the glycolysis pathway, this intermediate can be converted into glucose storage molecules, such as glycogen or starch . The reverse reaction, breaking down, e.g., glycogen, produces mainly glucose-6-phosphate; very little free glucose is formed in the reaction. The glucose-6-phosphate so produced can enter glycolysis after the first control point.
In the second regulated step (the third step of glycolysis), phosphofructokinase converts fructose-6-phosphate into fructose-1,6-bisphosphate, which then is converted into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. The dihydroxyacetone phosphate can be removed from glycolysis by conversion into glycerol-3-phosphate, which can be used to form triglycerides. [ 21 ] Conversely, triglycerides can be broken down into fatty acids and glycerol; the latter, in turn, can be converted into dihydroxyacetone phosphate, which can enter glycolysis after the second control point.
The change in free energy, Δ G , for each step in the glycolysis pathway can be calculated using Δ G = Δ G °′ + RT ln Q , where Q is the reaction quotient . This requires knowing the concentrations of the metabolites . All of these values are available for erythrocytes , with the exception of the concentrations of NAD + and NADH. The ratio of NAD + to NADH in the cytoplasm is approximately 1000, which makes the oxidation of glyceraldehyde-3-phosphate (step 6) more favourable.
Using the measured concentrations of each step, and the standard free energy changes, the actual free energy change can be calculated. (Neglecting this is very common—the delta G of ATP hydrolysis in cells is not the standard free energy change of ATP hydrolysis quoted in textbooks).
From measuring the physiological concentrations of metabolites in an erythrocyte it seems that about seven of the steps in glycolysis are in equilibrium for that cell type. Three of the steps—the ones with large negative free energy changes—are not in equilibrium and are referred to as irreversible ; such steps are often subject to regulation.
Step 5 in the figure is shown behind the other steps, because that step is a side-reaction that can decrease or increase the concentration of the intermediate glyceraldehyde-3-phosphate. That compound is converted to dihydroxyacetone phosphate by the enzyme triose phosphate isomerase, which is a catalytically perfect enzyme; its rate is so fast that the reaction can be assumed to be in equilibrium. The fact that Δ G is not zero indicates that the actual concentrations in the erythrocyte are not accurately known.
The enzymes that catalyse glycolysis are regulated via a range of biological mechanisms in order to control overall flux though the pathway. This is vital for both homeostatsis in a static environment, and metabolic adaptation to a changing environment or need. [ 23 ] The details of regulation for some enzymes are highly conserved between species, whereas others vary widely. [ 24 ] [ 25 ]
In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of homeostasis . The beta cells in the pancreatic islets are sensitive to the blood glucose concentration. [ 32 ] A rise in the blood glucose concentration causes them to release insulin into the blood, which has an effect particularly on the liver, but also on fat and muscle cells, causing these tissues to remove glucose from the blood. When the blood sugar falls the pancreatic beta cells cease insulin production, but, instead, stimulate the neighboring pancreatic alpha cells to release glucagon into the blood. [ 32 ] This, in turn, causes the liver to release glucose into the blood by breaking down stored glycogen , and by means of gluconeogenesis. If the fall in the blood glucose level is particularly rapid or severe, other glucose sensors cause the release of epinephrine from the adrenal glands into the blood. This has the same action as glucagon on glucose metabolism, but its effect is more pronounced. [ 32 ] In the liver glucagon and epinephrine cause the phosphorylation of the key, regulated enzymes of glycolysis, fatty acid synthesis , cholesterol synthesis , gluconeogenesis, and glycogenolysis. Insulin has the opposite effect on these enzymes. [ 33 ] The phosphorylation and dephosphorylation of these enzymes (ultimately in response to the glucose level in the blood) is the dominant manner by which these pathways are controlled in the liver, fat, and muscle cells. Thus the phosphorylation of phosphofructokinase inhibits glycolysis, whereas its dephosphorylation through the action of insulin stimulates glycolysis. [ 33 ]
The three regulatory enzymes are hexokinase (or glucokinase in the liver), phosphofructokinase , and pyruvate kinase . The flux through the glycolytic pathway is adjusted in response to conditions both inside and outside the cell. The internal factors that regulate glycolysis do so primarily to provide ATP in adequate quantities for the cell's needs. The external factors act primarily on the liver , fat tissue , and muscles , which can remove large quantities of glucose from the blood after meals (thus preventing hyperglycemia by storing the excess glucose as fat or glycogen, depending on the tissue type). The liver is also capable of releasing glucose into the blood between meals, during fasting, and exercise thus preventing hypoglycemia by means of glycogenolysis and gluconeogenesis . These latter reactions coincide with the halting of glycolysis in the liver.
In addition hexokinase and glucokinase act independently of the hormonal effects as controls at the entry points of glucose into the cells of different tissues. Hexokinase responds to the glucose-6-phosphate (G6P) level in the cell, or, in the case of glucokinase, to the blood sugar level in the blood to impart entirely intracellular controls of the glycolytic pathway in different tissues (see below ). [ 33 ]
When glucose has been converted into G6P by hexokinase or glucokinase, it can either be converted to glucose-1-phosphate (G1P) for conversion to glycogen , or it is alternatively converted by glycolysis to pyruvate , which enters the mitochondrion where it is converted into acetyl-CoA and then into citrate . Excess citrate is exported from the mitochondrion back into the cytosol, where ATP citrate lyase regenerates acetyl-CoA and oxaloacetate (OAA). The acetyl-CoA is then used for fatty acid synthesis and cholesterol synthesis , two important ways of utilizing excess glucose when its concentration is high in blood. The regulated enzymes catalyzing these reactions perform these functions when they have been dephosphorylated through the action of insulin on the liver cells. Between meals, during fasting , exercise or hypoglycemia, glucagon and epinephrine are released into the blood. This causes liver glycogen to be converted back to G6P, and then converted to glucose by the liver-specific enzyme glucose 6-phosphatase and released into the blood. Glucagon and epinephrine also stimulate gluconeogenesis, which converts non-carbohydrate substrates into G6P, which joins the G6P derived from glycogen, or substitutes for it when the liver glycogen store have been depleted. This is critical for brain function, since the brain utilizes glucose as an energy source under most conditions. [ 34 ] The simultaneously phosphorylation of, particularly, phosphofructokinase , but also, to a certain extent pyruvate kinase, prevents glycolysis occurring at the same time as gluconeogenesis and glycogenolysis.
All cells contain the enzyme hexokinase , which catalyzes the conversion of glucose that has entered the cell into glucose-6-phosphate (G6P). Since the cell membrane is impervious to G6P, hexokinase essentially acts to transport glucose into the cells from which it can then no longer escape. Hexokinase is inhibited by high levels of G6P in the cell. Thus the rate of entry of glucose into cells partially depends on how fast G6P can be disposed of by glycolysis, and by glycogen synthesis (in the cells which store glycogen, namely liver and muscles). [ 33 ] [ 35 ]
Glucokinase , unlike hexokinase, is not inhibited by G6P. It occurs in liver cells, and will only phosphorylate the glucose entering the cell to form G6P, when the glucose in the blood is abundant. This being the first step in the glycolytic pathway in the liver, it therefore imparts an additional layer of control of the glycolytic pathway in this organ. [ 33 ]
Phosphofructokinase is an important control point in the glycolytic pathway, since it is one of the irreversible steps and has key allosteric effectors, AMP and fructose 2,6-bisphosphate (F2,6BP).
F2,6BP is a very potent activator of phosphofructokinase (PFK-1) that is synthesized when F6P is phosphorylated by a second phosphofructokinase ( PFK2 ). In the liver, when blood sugar is low and glucagon elevates cAMP, PFK2 is phosphorylated by protein kinase A . The phosphorylation inactivates PFK2, and another domain on this protein becomes active as fructose bisphosphatase-2 , which converts F2,6BP back to F6P. Both glucagon and epinephrine cause high levels of cAMP in the liver. The result of lower levels of liver F2,6BP is a decrease in activity of phosphofructokinase and an increase in activity of fructose 1,6-bisphosphatase , so that gluconeogenesis (in essence, "glycolysis in reverse") is favored. This is consistent with the role of the liver in such situations, since the response of the liver to these hormones is to release glucose to the blood.
ATP competes with AMP for the allosteric effector site on the PFK enzyme. ATP concentrations in cells are much higher than those of AMP, typically 100-fold higher, [ 36 ] but the concentration of ATP does not change more than about 10% under physiological conditions, whereas a 10% drop in ATP results in a 6-fold increase in AMP. [ 37 ] Thus, the relevance of ATP as an allosteric effector is questionable. An increase in AMP is a consequence of a decrease in energy charge in the cell.
Citrate inhibits phosphofructokinase when tested in vitro by enhancing the inhibitory effect of ATP. However, it is doubtful that this is a meaningful effect in vivo , because citrate in the cytosol is utilized mainly for conversion to acetyl-CoA for fatty acid and cholesterol synthesis.
TIGAR , a p53 induced enzyme, is responsible for the regulation of phosphofructokinase and acts to protect against oxidative stress. [ 38 ] TIGAR is a single enzyme with dual function that regulates F2,6BP. It can behave as a phosphatase (fructuose-2,6-bisphosphatase) which cleaves the phosphate at carbon-2 producing F6P. It can also behave as a kinase (PFK2) adding a phosphate onto carbon-2 of F6P which produces F2,6BP. In humans, the TIGAR protein is encoded by C12orf5 gene. The TIGAR enzyme will hinder the forward progression of glycolysis, by creating a build up of fructose-6-phosphate (F6P) which is isomerized into glucose-6-phosphate (G6P). The accumulation of G6P will shunt carbons into the pentose phosphate pathway. [ 39 ] [ 40 ]
The final step of glycolysis is catalysed by pyruvate kinase to form pyruvate and another ATP. It is regulated by a range of different transcriptional, covalent and non-covalent regulation mechanisms, which can vary widely in different tissues. [ 41 ] [ 42 ] [ 43 ] For example, in the liver, pyruvate kinase is regulated based on glucose availability. During fasting (no glucose available), glucagon activates protein kinase A which phosphorylates pyruvate kinase to inhibit it. [ 44 ] An increase in blood sugar leads to secretion of insulin , which activates protein phosphatase 1 , leading to dephosphorylation and re-activation of pyruvate kinase. [ 44 ] These controls prevent pyruvate kinase from being active at the same time as the enzymes that catalyze the reverse reaction ( pyruvate carboxylase and phosphoenolpyruvate carboxykinase ), preventing a futile cycle . [ 44 ] Conversely, the isoform of pyruvate kinasein found in muscle is not affected by protein kinase A (which is activated by adrenaline in that tissue), so that glycolysis remains active in muscles even during fasting. [ 44 ]
The overall process of glycolysis is:
If glycolysis were to continue indefinitely, all of the NAD + would be used up, and glycolysis would stop. To allow glycolysis to continue, organisms must be able to oxidize NADH back to NAD + . How this is performed depends on which external electron acceptor is available.
One method of doing this is to simply have the pyruvate do the oxidation; in this process, pyruvate is converted to lactate (the conjugate base of lactic acid) in a process called lactic acid fermentation :
This process occurs in the bacteria involved in making yogurt (the lactic acid causes the milk to curdle). This process also occurs in animals under hypoxic (or partially anaerobic) conditions, found, for example, in overworked muscles that are starved of oxygen. In many tissues, this is a cellular last resort for energy; most animal tissue cannot tolerate anaerobic conditions for an extended period of time.
Some organisms, such as yeast, convert NADH back to NAD + in a process called ethanol fermentation . In this process, the pyruvate is converted first to acetaldehyde and carbon dioxide, and then to ethanol.
Lactic acid fermentation and ethanol fermentation can occur in the absence of oxygen. This anaerobic fermentation allows many single-cell organisms to use glycolysis as their only energy source.
Anoxic regeneration of NAD + is only an effective means of energy production during short, intense exercise in vertebrates, for a period ranging from 10 seconds to 2 minutes during a maximal effort in humans. (At lower exercise intensities it can sustain muscle activity in diving animals , such as seals, whales and other aquatic vertebrates, for very much longer periods of time.) Under these conditions NAD + is replenished by NADH donating its electrons to pyruvate to form lactate. This produces 2 ATP molecules per glucose molecule, or about 5% of glucose's energy potential (38 ATP molecules in bacteria). But the speed at which ATP is produced in this manner is about 100 times that of oxidative phosphorylation. The pH in the cytoplasm quickly drops when hydrogen ions accumulate in the muscle, eventually inhibiting the enzymes involved in glycolysis.
The burning sensation in muscles during hard exercise can be attributed to the release of hydrogen ions during the shift to glucose fermentation from glucose oxidation to carbon dioxide and water, when aerobic metabolism can no longer keep pace with the energy demands of the muscles. These hydrogen ions form a part of lactic acid. The body falls back on this less efficient but faster method of producing ATP under low oxygen conditions. This is thought to have been the primary means of energy production in earlier organisms before oxygen reached high concentrations in the atmosphere between 2000 and 2500 million years ago, and thus would represent a more ancient form of energy production than the aerobic replenishment of NAD + in cells.
The liver in mammals gets rid of this excess lactate by transforming it back into pyruvate under aerobic conditions; see Cori cycle .
Fermentation of pyruvate to lactate is sometimes also called "anaerobic glycolysis", however, glycolysis ends with the production of pyruvate regardless of the presence or absence of oxygen.
In the above two examples of fermentation, NADH is oxidized by transferring two electrons to pyruvate. However, anaerobic bacteria use a wide variety of compounds as the terminal electron acceptors in cellular respiration : nitrogenous compounds, such as nitrates and nitrites; sulfur compounds, such as sulfates, sulfites, sulfur dioxide, and elemental sulfur; carbon dioxide; iron compounds; manganese compounds; cobalt compounds; and uranium compounds.
In aerobic eukaryotes , a complex mechanism has developed to use the oxygen in air as the final electron acceptor, in a process called oxidative phosphorylation . Aerobic prokaryotes , which lack mitochondria, use a variety of simpler mechanisms .
The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol . [ 46 ] This occurs via the conversion of pyruvate into acetyl-CoA in the mitochondrion . However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate ) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol . [ 46 ] There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). The cytosolic acetyl-CoA can be carboxylated by acetyl-CoA carboxylase into malonyl CoA , the first committed step in the synthesis of fatty acids , or it can be combined with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA ( HMG-CoA ) which is the rate limiting step controlling the synthesis of cholesterol . [ 47 ] Cholesterol can be used as is, as a structural component of cellular membranes, or it can be used to synthesize the steroid hormones , bile salts , and vitamin D . [ 35 ] [ 46 ] [ 47 ]
Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO 2 , acetyl-CoA, and NADH, [ 35 ] or they can be carboxylated (by pyruvate carboxylase ) to form oxaloacetate . This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle, and is therefore an anaplerotic reaction (from the Greek meaning to "fill up"), increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. in heart and skeletal muscle ) are suddenly increased by activity. [ 48 ] In the citric acid cycle all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that that additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence the addition of oxaloacetate greatly increases the amounts of all the citric acid intermediates, thereby increasing the cycle's capacity to metabolize acetyl CoA, converting its acetate component into CO 2 and water, with the release of enough energy to form 11 ATP and 1 GTP molecule for each additional molecule of acetyl CoA that combines with oxaloacetate in the cycle. [ 48 ]
To cataplerotically remove oxaloacetate from the citric cycle, malate can be transported from the mitochondrion into the cytoplasm, decreasing the amount of oxaloacetate that can be regenerated. [ 48 ] Furthermore, citric acid intermediates are constantly used to form a variety of substances such as the purines, pyrimidines and porphyrins . [ 48 ]
This article concentrates on the catabolic role of glycolysis with regard to converting potential chemical energy to usable chemical energy during the oxidation of glucose to pyruvate. Many of the metabolites in the glycolytic pathway are also used by anabolic pathways, and, as a consequence, flux through the pathway is critical to maintain a supply of carbon skeletons for biosynthesis. [ 49 ]
The following metabolic pathways are all strongly reliant on glycolysis as a source of metabolites: and many more.
Although gluconeogenesis and glycolysis share many intermediates the one is not functionally a branch or tributary of the other. There are two regulatory steps in both pathways which, when active in the one pathway, are automatically inactive in the other. The two processes can therefore not be simultaneously active. [ 50 ] Indeed, if both sets of reactions were highly active at the same time the net result would be the hydrolysis of four high energy phosphate bonds (two ATP and two GTP) per reaction cycle. [ 50 ]
NAD + is the oxidizing agent in glycolysis, as it is in most other energy yielding metabolic reactions (e.g. beta-oxidation of fatty acids, and during the citric acid cycle ). The NADH thus produced is primarily used to ultimately transfer electrons to O 2 to produce water, or, when O 2 is not available, to produce compounds such as lactate or ethanol (see Anoxic regeneration of NAD + above). NADH is rarely used for synthetic processes, the notable exception being gluconeogenesis. During fatty acid and cholesterol synthesis the reducing agent is NADPH . This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions. [ 50 ] The source of the NADPH is two-fold. When malate is oxidatively decarboxylated by "NADP + -linked malic enzyme" pyruvate , CO 2 and NADPH are formed. NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids , or it can be catabolized to pyruvate. [ 50 ]
Cellular uptake of glucose occurs in response to insulin signals, and glucose is subsequently broken down through glycolysis, lowering blood sugar levels. However, insulin resistance or low insulin levels seen in diabetes result in hyperglycemia, where glucose levels in the blood rise and glucose is not properly taken up by cells. Hepatocytes further contribute to this hyperglycemia through gluconeogenesis . Glycolysis in hepatocytes controls hepatic glucose production, and when glucose is overproduced by the liver without having a means of being broken down by the body, hyperglycemia results. [ 51 ]
Glycolytic mutations are generally rare due to importance of the metabolic pathway; the majority of occurring mutations result in an inability of the cell to respire, and therefore cause the death of the cell at an early stage. However, some mutations ( glycogen storage diseases and other inborn errors of carbohydrate metabolism ) are seen with one notable example being pyruvate kinase deficiency , leading to chronic hemolytic anemia. [ citation needed ]
In combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency, glycolysis is reduced by -50%, which is caused by reduced lipoylation of mitochondrial enzymes such as the pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex . [ 52 ]
Malignant tumor cells perform glycolysis at a rate that is ten times faster than their noncancerous tissue counterparts. [ 53 ] During their genesis, limited capillary support often results in hypoxia (decreased O2 supply) within the tumor cells. Thus, these cells rely on anaerobic metabolic processes such as glycolysis for ATP (adenosine triphosphate). Some tumor cells overexpress specific glycolytic enzymes which result in higher rates of glycolysis. [ 54 ] Often these enzymes are Isoenzymes, of traditional glycolysis enzymes, that vary in their susceptibility to traditional feedback inhibition. The increase in glycolytic activity ultimately counteracts the effects of hypoxia by generating sufficient ATP from this anaerobic pathway. [ 55 ] This phenomenon was first described in 1930 by Otto Warburg and is referred to as the Warburg effect . The Warburg hypothesis claims that cancer is primarily caused by dysfunctionality in mitochondrial metabolism, rather than because of the uncontrolled growth of cells.
A number of theories have been advanced to explain the Warburg effect. One such theory suggests that the increased glycolysis is a normal protective process of the body and that malignant change could be primarily caused by energy metabolism. [ 56 ]
This high glycolysis rate has important medical applications, as high aerobic glycolysis by malignant tumors is utilized clinically to diagnose and monitor treatment responses of cancers by imaging uptake of 2- 18 F-2-deoxyglucose (FDG) (a radioactive modified hexokinase substrate ) with positron emission tomography (PET). [ 57 ] [ 58 ]
There is ongoing research to affect mitochondrial metabolism and treat cancer by reducing glycolysis and thus starving cancerous cells in various new ways, including a ketogenic diet . [ 59 ] [ 60 ] [ 61 ]
The diagram below shows human protein names. Names in other organisms may be different and the number of isozymes (such as HK1, HK2, ...) is likely to be different too.
Click on genes, proteins and metabolites below to link to respective articles. [ § 1 ]
Some of the metabolites in glycolysis have alternative names and nomenclature. In part, this is because some of them are common to other pathways, such as the Calvin cycle .
The intermediates of glycolysis depicted in Fischer projections show the chemical changing step by step. Such image can be compared to polygonal model representation. [ 62 ] | https://en.wikipedia.org/wiki/Glycolysis |
In biochemistry , a glycolytic oscillation is the repetitive fluctuation of in the concentrations of metabolites , [ 1 ] classically observed experimentally in yeast and muscle. [ 2 ] The first observations of oscillatory behaviour in glycolysis were made by Duysens and Amesz in 1957. [ 3 ] Glycolytic oscillations are typically induced in dense suspensions of cells exposed to glucose under anaerobic or semi- anaerobic conditions. [ 4 ] [ 5 ]
The problem of modelling glycolytic oscillation has been studied in control theory and dynamical systems since the 1960s [ 1 ] since the behaviour depends on the rate of substrate injection.
Early models used two variables, but the most complex behaviour they could demonstrate was period oscillations due to the Poincaré–Bendixson theorem , so later models introduced further variables. [ 6 ]
Glycolytic oscillations are driven by feedback within the glycolytic pathway, where fluctuations in metabolite concentrations synchronize with other cellular processes. These oscillations are tightly coupled with mitochondrial membrane potential, mediated by the ADP/ATP antiporter and the F 0 F 1 - ATPase. The ATP/ADP ratio and proton gradients generated by these processes play a central role in this coupling. Experimental evidence shows that inhibitors targeting glycolysis, such as 2-deoxyglucose or iodoacetate, stop both NADH and mitochondrial membrane potential oscillations, highlighting the enzymatic regulation within the glycolytic pathway. [ 5 ]
Mathematical models and experimental data further reveal that oscillations in mitochondrial membrane potential are in phase with NADH fluctuations. These synchronized dynamics show how energy metabolism and glycolysis are interconnected, with mitochondrial activity responding to changes in glycolytic flux. [ 5 ]
Potassium (K + ) is essential for glycolytic oscillations, with intracellular K + concentrations oscillating in phase with NADH, ATP, and mitochondrial membrane potential. Mutants lacking K + transporters, such as the mitochondrial K + /H + exchanger Mdm38p or the endosomal Nhx1p, fail to exhibit oscillatory behavior. Introducing the ionophore nigericin restores oscillation in Mdm38p-deficient strains, demonstrating the critical role of K + /H + exchange in sustaining glycolysis. [ 4 ]
Potassium contributes to intracellular pH regulation and enzymatic activity in glycolysis, Reduced extracellular K + levels decrease the amplitude of oscillations, confirming its importance in regulation. [ 4 ] | https://en.wikipedia.org/wiki/Glycolytic_oscillation |
GlycomeDB is a database of carbohydrates including structural and taxonomic data. [ 1 ]
This Biological database -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/GlycomeDB |
Glycomics is the comprehensive study of glycomes [ 1 ] (the entire complement of sugars , whether free or present in more complex molecules of an organism ), including genetic, physiologic, pathologic, and other aspects. [ 2 ] [ 3 ] Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology . [ 4 ] The term glycomics is derived from the chemical prefix for sweetness or a sugar, "glyco-", and was formed to follow the omics naming convention established by genomics (which deals with genes ) and proteomics (which deals with proteins ).
This area of research has to deal with an inherent level of complexity not seen in other areas of applied biology. [ 5 ] 68 building blocks (molecules for DNA, RNA and proteins; categories for lipids; types of sugar linkages for saccharides) provide the structural basis for the molecular choreography that constitutes the entire life of a cell. DNA and RNA have four building blocks each (the nucleosides or nucleotides ). Lipids are divided into eight categories based on ketoacyl and isoprene . Proteins have 20 (the amino acids ). Saccharides have 32 types of sugar linkages. [ 6 ] While these building blocks can be attached only linearly for proteins and genes, they can be arranged in a branched array for saccharides, further increasing the degree of complexity.
Add to this the complexity of the numerous proteins involved, not only as carriers of carbohydrate, the glycoproteins , but proteins specifically involved in binding and reacting with carbohydrate:
To answer this question one should know the different and important functions of glycans. The following are some of those functions:
There are important medical applications of aspects of glycomics:
Glycomics is particularly important in microbiology because glycans play diverse roles in bacterial physiology. [ 7 ] Research in bacterial glycomics could lead to the development of:
The following are examples of the commonly used techniques in glycan analysis [ 4 ] [ 5 ]
The most commonly applied methods are MS and HPLC , in which the glycan part is cleaved either enzymatically or chemically from the target and subjected to analysis. [ 8 ] In case of glycolipids, they can be analyzed directly without separation of the lipid component.
N- glycans from glycoproteins are analyzed routinely by high-performance-liquid-chromatography (reversed phase, normal phase and ion exchange HPLC) after tagging the reducing end of the sugars with a fluorescent compound (reductive labeling). [ 9 ] A large variety of different labels were introduced in the recent years, where 2-aminobenzamide (AB), anthranilic acid (AA), 2-aminopyridin (PA), 2-aminoacridone (AMAC) and 3-(acetylamino)-6-aminoacridine (AA-Ac) are just a few of them. [ 10 ]
O- glycans are usually analysed without any tags, due to the chemical release conditions preventing them to be labeled. [ 11 ]
Fractionated glycans from high-performance liquid chromatography (HPLC) instruments can be further analyzed by MALDI -TOF-MS(MS) to get further information about structure and purity. Sometimes glycan pools are analyzed directly by mass spectrometry without prefractionation, although a discrimination between isobaric glycan structures is more challenging or even not always possible. Anyway, direct MALDI -TOF-MS analysis can lead to a fast and straightforward illustration of the glycan pool. [ 12 ]
In recent years, high performance liquid chromatography online coupled to mass spectrometry became very popular. By choosing porous graphitic carbon as a stationary phase for liquid chromatography, even non derivatized glycans can be analyzed. Electrospray ionisation ( ESI ) is frequently used for this application. [ 13 ] [ 14 ] [ 15 ]
Although MRM has been used extensively in metabolomics and proteomics, its high sensitivity and linear response over a wide dynamic range make it especially suited for glycan biomarker research and discovery. MRM is performed on a triple quadrupole (QqQ) instrument, which is set to detect a predetermined precursor ion in the first quadrupole, a fragmented in the collision quadrupole, and a predetermined fragment ion in the third quadrupole. It is a non-scanning technique, wherein each transition is detected individually and the detection of multiple transitions occurs concurrently in duty cycles. This technique is being used to characterize the immune glycome. [ 16 ] [ 17 ] [ 18 ]
Table 1 : Advantages and disadvantages of mass spectrometry in glycan analysis
Lectin and antibody arrays provide high-throughput screening of many samples containing glycans. This method uses either naturally occurring lectins or artificial monoclonal antibodies , where both are immobilized on a certain chip and incubated with a fluorescent glycoprotein sample.
Glycan arrays, like that offered by the Consortium for Functional Glycomics and Z Biotech LLC , contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands.
Metabolic labeling of glycans can be used as a way to detect glycan structures. A well known strategy involves the use of azide -labeled sugars which can be reacted using the Staudinger ligation . This method has been used for in vitro and in vivo imaging of glycans.
X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy for complete structural analysis of complex glycans is a difficult and complex field. However, the structure of the binding site of numerous lectins , enzymes and other carbohydrate-binding proteins has revealed a wide variety of the structural basis for glycome function. The purity of test samples have been obtained through chromatography ( affinity chromatography etc.) and analytical electrophoresis ( PAGE (polyacrylamide electrophoresis) , capillary electrophoresis , affinity electrophoresis , etc.).
There are several on-line software and databases available for glycomic research. This includes: | https://en.wikipedia.org/wiki/Glycomics |
Glycomimetic is a term used to refer to molecules that have structures similar to carbohydrates , but with some variation. [ 1 ] This will normally result in modified biological properties.
Often, modification of the structure will take place around the glycosidic linkage . Replacement of one or other of the glycosidic oxygen atoms by carbon, sulfur, nitrogen etc. will alter the properties of the glycosidic bond. The molecules produced in this way would be called carbasugars or C-glycosides , thiosugars or thioglycosides , or iminosugars or glycosylamines .
When nitrogen is introduced, the glycomimetic may become positively charged at physiological pH, meaning that it may act as an enzyme inhibitor , either by Coulombic interaction with carboxylate amino acid side-chains in the enzyme active site , or by mimicking positive-charge build-up at the transition state of the reaction, or both. Iminosugars (sometimes referred to erroneously as azasugars) are classic examples of molecules with this behaviour. Glycosylamines typically have a lower stability, being easily hydrolysed, which means that to exploit an exocyclic nitrogen substituent at C-1, further modification is necessary. An example of this would be the additional substitution of the ring-oxygen for carbon as is seen in valienamine .
Altering the structure of a carbohydrate will normally result in several changes to the properties of the molecule. As well as changing the stability of the glycosidic bond, the ring-conformation may be affected. Also the conformation of the glycosidic bond may be affected. As well as obvious changes in the immediate vicinity of the substitution, e.g. that replacement of an acetal oxygen by methylene (CH2) would result in loss of a hydrogen-bond participatory atom, such a substitution is expected to have more subtle effects resulting from a change in the dipole of the molecule, such as slight changes in hydrogen bonding or pKa values of the unchanged hydroxyl groups. Substitution by CF2 rather than methylene has been explored [ 2 ] in efforts to address this and come up with better mimetics while still retaining the hydrolytic stability gained by the modification.
Tamiflu is a carbocyclic mimic of the cell-surface carbohydrate sialic acid . Tamiflu is an enzyme inhibitor that blocks the action of influenza virus neuraminidases (sialidases).
Acarbose is a pseudotetrasaccharide mimicking maltotetraose (a substructure of starch ). One of the glucose units has been replaced by valienamine - a carbasugar , linked to the next carbohydrate by an amine bridge. Another of the glucose units appears as a 6-deoxy variant. Acarbose is an enzyme inhibitor that is used as a drug against type 2 diabetes .
Miglustat is an iminosugar in which the ring oxygen is replaced by nitrogen. Miglustat a drug used to treat some rare lysosomal storage disorder diseases. | https://en.wikipedia.org/wiki/Glycomimetic |
Glyconeogenesis is the synthesis of glycogen without using glucose or other carbohydrates , instead using substances like proteins and fats . This includes substrates like glycerol, lactate, glutamine and alanine. [ 1 ] It's used in replenishing glycogen stores when glucose is limited, [ 2 ] like after long periods of fasting. [ 3 ] In the liver and kidneys, it uses the enzymes phosphoenolpyruvate carboxykinase 2 and fructose-1,6-bisphophatase 1, [ 1 ] and fructose-1,6-bisphosphatase 2 in skeletal muscle. [ 2 ] One example is the conversion of lactic acid to glycogen in the liver . [ 4 ] [ full citation needed ] Lactic acid is converted to alanine, the alanine is transferred to the liver, and once in the liver is it converted back to alanine where it is free to be transformed into glucose. [ 3 ]
This article about medicinal chemistry is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Glyconeogenesis |
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