Many plants engage in  symbiosis  with microorganisms.  Two important types of these relationship are


The Earth's atmosphere contains over 78 percent nitrogen. Plants called legumes, including the agricultural crops alfalfa and soybeans, widely grown by farmers, harbour nitrogen-fixing bacteria that can convert atmospheric nitrogen into nitrogen the plant can use. Plants not classified as legumes such as wheat, corn and rice rely on nitrogen compounds present in the soil to support their growth. These can be supplied by  mineralization  of  soil organic matter  or added plant residues, nitrogen fixing bacteria, animal waste, through the breaking of triple bonded N 2  molecules by lightning strikes or through the application of  fertilizers .


At least 17 elements are known to be essential nutrients for plants. In relatively large amounts, the soil supplies nitrogen, phosphorus, potassium, calcium, magnesium, and sulfur; these are often called the  macronutrients . In relatively small amounts, the  soil  supplies iron, manganese, boron, molybdenum, copper, zinc, chlorine, and cobalt, the so-called  micronutrients . Nutrients must be available not only in sufficient amounts but also in appropriate ratios.


Plant nutrition is a difficult subject to understand completely, partially because of the variation between different plants and even between different species or individuals of a given clone. Elements present at low levels may cause deficiency symptoms, and toxicity is possible at levels that are too high. Furthermore, deficiency of one element may present as symptoms of toxicity from another element, and vice versa. An abundance of one nutrient may cause a deficiency of another nutrient. For example, K +  uptake can be influenced by the amount of NH + 4  available. [ 6 ]


Nitrogen is plentiful in the Earth's atmosphere, and a number of commercially-important agricultural plants engage in  nitrogen fixation  (conversion of atmospheric nitrogen to a biologically useful form). However, plants mostly receive their nitrogen through the soil, where it is already converted in biological useful form. This is important because the nitrogen in the atmosphere is too large for the plant to consume, and takes a lot of energy to convert into smaller forms. These include soybeans, edible beans and peas as well as clovers and alfalfa used primarily for feeding livestock.  Plants such as the commercially-important corn, wheat, oats, barley and rice require nitrogen compounds to be present in the soil in which they grow.


Carbon and oxygen are absorbed from the air while other nutrients are absorbed from the soil.  Green plants  ordinarily obtain their carbohydrate supply from the carbon dioxide in the air by the process of  photosynthesis . Each of these nutrients is used for a different essential function. [ 7 ]


The basic nutrients are derived from air and water. [ 8 ]


Carbon  forms the backbone of most plant  biomolecules , including proteins,  starches  and  cellulose .   Carbon is fixed  through  photosynthesis ; this converts  carbon dioxide  from the air into  carbohydrates  which are used to store and transport energy within the plant.


Hydrogen  is necessary for building sugars and building the plant. It is obtained almost entirely from water. Hydrogen ions are imperative for a proton gradient to help drive the electron transport chain in photosynthesis and for respiration. [ 6 ]


Oxygen  is a component of many organic and inorganic molecules within the plant, and is acquired in many forms. These include:  O 2  and  CO 2  (mainly from the air via leaves) and  H 2 O ,  NO − 3 ,  H 2 PO − 4  and  SO 2− 4  (mainly from the soil water via roots). Plants produce oxygen gas (O 2 ) along with  glucose  during  photosynthesis  but then require O 2  to undergo aerobic  cellular respiration  and break down this glucose to produce  ATP .


Nitrogen  is a major constituent of several of the most important plant substances. For example, nitrogen compounds comprise 40% to 50% of the dry matter of  protoplasm , and it is a constituent of  amino acids , the building blocks of  proteins . [ 9 ]  It is also an essential constituent of  chlorophyll . [ 10 ]  In many agricultural settings, nitrogen is the limiting nutrient for rapid growth.


Like nitrogen,  phosphorus  is involved with many vital plant processes. Within a plant, it is present mainly as a structural component of the  nucleic acids :  deoxyribonucleic acid  (DNA) and  ribonucleic acid  (RNA), as well as a constituent of fatty  phospholipids , that are important in membrane development and function. It is present in both organic and inorganic forms, both of which are readily translocated within the plant. All energy transfers in the cell are critically dependent on phosphorus.  As with all living things, phosphorus is part of the  Adenosine triphosphate  (ATP), which is of immediate use in all processes that require energy with the cells. Phosphorus can also be used to modify the activity of various enzymes by  phosphorylation , and is used for  cell signaling . Phosphorus is concentrated at the most actively growing points of a plant and stored within seeds in anticipation of their germination.


Unlike other major elements,  potassium  does not enter into the composition of any of the important plant constituents involved in metabolism, [ 9 ]  but it does occur in all parts of plants in substantial amounts. It is essential for enzyme activity including enzymes involved in primary metabolism. It plays a role in  turgor  regulation, effecting the functioning of the stomata and cell volume growth. [ 11 ]


It seems to be of particular importance in leaves and at growing points. Potassium is outstanding among the nutrient elements for its mobility and solubility within plant tissues.


Processes involving potassium include the formation of  carbohydrates  and  proteins , the regulation of internal plant moisture, as a catalyst and condensing agent of complex substances, as an accelerator of enzyme action, and as contributor to  photosynthesis , especially under low light intensity. Potassium regulates the opening and closing of the  stomata  by a potassium ion pump. Since stomata are important in water regulation, potassium regulates water loss from the leaves and increases  drought  tolerance. Potassium serves as an activator of enzymes used in photosynthesis and respiration. [ 6 ]  Potassium is used to build cellulose and aids in photosynthesis by the formation of a chlorophyll precursor. The potassium ion (K + ) is highly mobile and can aid in balancing the anion (negative) charges within the plant. A relationship between potassium nutrition and cold resistance has been found in several tree species, including two species of spruce. [ 12 ]  Potassium helps in fruit coloration, shape and also increases its  brix . Hence, quality fruits are produced in potassium-rich soils.


Research has linked K +  transport with auxin homeostasis, cell signaling, cell expansion, membrane trafficking and phloem transport. [ 11 ]


Sulfur  is a structural component of some amino acids (including  cystein  and  methionine ) and vitamins, and is essential for  chloroplast  growth and function; it is found in the iron-sulfur complexes of the electron transport chains in photosynthesis. It is needed for N 2  fixation by legumes, and the conversion of nitrate into amino acids and then into protein. [ 13 ]


Calcium  in plants occurs chiefly in the  leaves , with lower concentrations in seeds, fruits, and roots. A major function is as a constituent of cell walls. When coupled with certain acidic compounds of the jelly-like pectins of the middle lamella, calcium forms an insoluble salt. It is also intimately involved in  meristems , and is particularly important in root development, with roles in cell division, cell elongation, and the detoxification of hydrogen ions. Other functions attributed to calcium are: the neutralization of organic acids; inhibition of some potassium-activated ions; and a role in nitrogen absorption. A notable feature of calcium-deficient plants is a defective root system. [ 14 ]  Roots are usually affected before above-ground parts. [ 15 ]   Blossom end rot  is also a result of inadequate calcium. [ 16 ]


Calcium  regulates transport of other nutrients into the plant and is also involved in the activation of certain plant enzymes.  Calcium deficiency  results in stunting. This nutrient is involved in photosynthesis and plant structure. [ 16 ] [ 17 ]  It is needed as a balancing  cation  for  anions  in the  vacuole  and as an  intracellular messenger  in the  cytosol . [ 18 ]


The outstanding role of  magnesium  in plant nutrition is as a constituent of the  chlorophyll  molecule. As a carrier, it is also involved in numerous enzyme reactions as an effective activator, in which it is closely associated with energy-supplying  phosphorus  compounds.


Plants are able sufficiently to accumulate most trace elements. Some plants are sensitive indicators of the chemical environment in which they grow (Dunn 1991), [ 19 ]  and some plants have barrier mechanisms that exclude or limit the uptake of a particular element or ion species, e.g., alder twigs commonly accumulate molybdenum but not arsenic, whereas the reverse is true of spruce bark (Dunn 1991). [ 19 ]  Otherwise, a plant can integrate the geochemical signature of the soil mass permeated by its root system together with the contained groundwaters. Sampling is facilitated by the tendency of many elements to accumulate in tissues at the plant's extremities. Some micronutrients can be applied as seed coatings.


Iron  is necessary for photosynthesis and is present as an enzyme cofactor in plants.  Iron deficiency  can result in interveinal  chlorosis  and  necrosis .
Iron is not a structural part of chlorophyll but very much essential for its synthesis. Copper deficiency can be responsible for promoting an iron deficiency. [ 20 ]
It helps in the electron transport of plant.


As with other biological processes, the main useful form of iron is that of iron(II) due to its higher solubility in neutral pH. However, plants are also capable of using iron(III) via citric acid, using the photo-reduction of  ferric citrate . [ 21 ]  In the field, as with many other transitional metal elements, iron fertilizer is supplied as a  chelate . [ 22 ]


Molybdenum  is a cofactor to enzymes important in building amino acids and is involved in nitrogen metabolism. Molybdenum is part of the  nitrate reductase  enzyme (needed for the reduction of nitrate) and the  nitrogenase  enzyme (required for  biological nitrogen fixation ). [ 10 ]  Reduced productivity as a result of  molybdenum deficiency  is usually associated with the reduced activity of one or more of these enzymes.


Boron has many functions in a plant: [ 23 ]  it affects flowering and fruiting, pollen germination, cell division, and active salt absorption. The metabolism of amino acids and proteins, carbohydrates, calcium, and water are strongly affected by boron. Many of those listed functions may be embodied by its function in moving the highly polar sugars through cell membranes by reducing their polarity and hence the energy needed to pass the sugar. If sugar cannot pass to the fastest growing parts rapidly enough, those parts die.


Copper  is important for photosynthesis. Symptoms for copper deficiency include chlorosis. It is involved in many enzyme processes; necessary for proper photosynthesis; involved in the manufacture of lignin (cell walls) and involved in grain production. It is difficult to find in some soil conditions.


Manganese  is necessary for photosynthesis, [ 17 ]  including the building of  chloroplasts .  Manganese deficiency  may result in coloration abnormalities, such as discolored spots on the  foliage .


Sodium  is involved in the regeneration of  phosphoenolpyruvate  in  CAM  and  C4  plants. Sodium can potentially replace potassium's regulation of stomatal opening and closing. [ 6 ]


Essentiality of sodium:


Zinc  is required in a large number of enzymes and plays an essential role in  DNA transcription . A typical symptom of  zinc deficiency  is the stunted growth of leaves, commonly known as "little leaf" and is caused by the oxidative degradation of the growth hormone  auxin .


In  vascular plants ,  nickel  is absorbed by plants in the form of Ni 2+  ion. Nickel is essential for activation of  urease , an enzyme involved with  nitrogen metabolism  that is required to process urea. Without nickel, toxic levels of urea accumulate, leading to the formation of necrotic lesions. In  non-vascular plants , nickel activates several enzymes involved in a variety of processes, and can substitute for zinc and iron as a cofactor in some enzymes. [ 24 ]


Chlorine , as compounded chloride, is necessary for  osmosis  and  ionic balance ; it also plays a role in  photosynthesis .


Cobalt  has proven to be beneficial to at least some plants although it does not appear to be essential for most species. [ 25 ]  It has, however, been shown to be essential for  nitrogen fixation  by the nitrogen-fixing bacteria associated with  legumes  and other plants. [ 25 ]


Silicon  is not considered an essential element for plant growth and development. It is always found in abundance in the environment and hence if needed it is available. It is found in the structures of plants and improves the health of plants. [ 26 ]


In plants,  silicon  has been shown in experiments to strengthen  cell walls , improve plant strength, health, and productivity. [ 27 ]  There have been studies showing evidence of silicon improving  drought  and  frost resistance , decreasing  lodging  potential and boosting the plant's natural pest and disease fighting systems. [ 28 ]  Silicon has also been shown to improve plant vigor and physiology by improving root mass and density, and increasing above ground plant  biomass  and  crop yields . [ 27 ]   Silicon is currently under consideration by the Association of American Plant Food Control Officials (AAPFCO) for elevation to the status of a "plant beneficial substance". [ 29 ] [ 30 ]


Vanadium  may be required by some plants, but at very low concentrations. It may also be substituting for  molybdenum .


Selenium  is probably not essential for flowering plants, but it can be beneficial; it can stimulate plant growth, improve tolerance of oxidative stress, and increase resistance to pathogens and herbivory. [ 31 ]


Nitrogen is transported via the xylem from the roots to the leaf canopy as nitrate ions, or in an organic form, such as amino acids or amides. Nitrogen can also be transported in the phloem sap as amides, amino acids and ureides; it is therefore mobile within the plant, and the older leaves exhibit chlorosis and necrosis earlier than the younger leaves. [ 6 ] [ 10 ]  Because phosphorus is a mobile nutrient, older leaves will show the first signs of deficiency. Magnesium is very mobile in plants, and, like potassium, when  deficient  is translocated from older to younger tissues, so that signs of deficiency appear first on the oldest tissues and then spread progressively to younger tissues.


Because calcium is  phloem  immobile, calcium deficiency can be seen in new growth. When developing tissues are forced to rely on the  xylem , calcium is supplied by  transpiration  only.


Boron is not relocatable in the plant via the  phloem . It must be supplied to the growing parts via the  xylem . Foliar sprays affect only those parts sprayed, which may be insufficient for the fastest growing parts, and is very temporary. [ citation needed ]


In plants, sulfur cannot be mobilized from older leaves for new growth, so deficiency symptoms are seen in the youngest tissues first. [ 32 ]  Symptoms of deficiency include yellowing of leaves and stunted growth. [ 33 ]


The effect of a nutrient deficiency can vary from a subtle depression of growth rate to obvious stunting, deformity, discoloration, distress, and even death. Visual symptoms distinctive enough to be useful in identifying a deficiency are rare. Most deficiencies are multiple and moderate. However, while a deficiency is seldom that of a single nutrient, nitrogen is commonly the nutrient in shortest supply.


Chlorosis  of foliage is not always due to mineral nutrient deficiency. Solarization can produce superficially similar effects, though mineral deficiency tends to cause premature defoliation, whereas solarization does not, nor does solarization depress nitrogen concentration. [ 34 ]


Nitrogen deficiency  most often results in stunted growth, slow growth, and chlorosis. Nitrogen deficient plants will also exhibit a purple appearance on the stems, petioles and underside of leaves from an accumulation of anthocyanin pigments. [ 6 ]


Phosphorus deficiency  can produce symptoms similar to those of nitrogen deficiency, [ 35 ]  characterized by an intense green coloration or reddening in leaves due to lack of chlorophyll. If the plant is experiencing high phosphorus deficiencies the leaves may become denatured and show signs of death. Occasionally the leaves may appear purple from an accumulation of  anthocyanin . As noted by Russel: [ 14 ]  "Phosphate deficiency differs from nitrogen deficiency in being extremely difficult to diagnose, and crops can be suffering from extreme starvation without there being any obvious signs that lack of phosphate is the cause". Russell's observation applies to at least some  coniferous  seedlings, but Benzian [ 36 ]  found that although response to phosphorus in very acid forest tree nurseries in England was consistently high, no species (including Sitka spruce) showed any visible symptom of deficiency other than a slight lack of lustre. Phosphorus levels have to be exceedingly low before visible symptoms appear in such seedlings. In sand culture at 0 ppm phosphorus, white spruce seedlings were very small and tinted deep purple; at 0.62 ppm, only the smallest seedlings were deep purple; at 6.2 ppm, the seedlings were of good size and color. [ 37 ] [ 38 ]


The root system is less effective without a continuous supply of calcium to newly developing cells. Even short term disruptions in calcium supply can disrupt biological functions and root function. [ 39 ]  A common symptom of calcium deficiency in leaves is the curling of the leaf towards the veins or center of the leaf. Many times this can also have a blackened appearance. [ 40 ]  The tips of the leaves may appear burned and cracking may occur in some calcium deficient crops if they experience a sudden increase in humidity. [ 18 ]  Calcium deficiency may arise in tissues that are fed by the  phloem , causing blossom end rot in watermelons, peppers and tomatoes, empty peanut pods and bitter pits in apples. In enclosed tissues, calcium deficiency can cause celery black heart and "brown heart" in greens like  escarole . [ 41 ]


Researchers found that partial deficiencies of K or P did not change the  fatty acid  composition of  phosphatidyl choline  in  Brassica napus L.  plants. Calcium deficiency did, on the other hand, lead to a marked decline of  polyunsaturated  compounds that would be expected to have negative impacts for integrity of the plant  membrane , that could effect some properties like its permeability, and is needed for the  ion  uptake activity of the root membranes. [ 42 ]


Potassium deficiency  may cause necrosis or  interveinal chlorosis . Deficiency may result in higher risk of pathogens, wilting, chlorosis, brown spotting, and higher chances of damage from frost and heat. When potassium is moderately deficient, the effects first appear in the older tissues, and from there progress towards the growing points. Acute deficiency severely affects growing points, and die-back commonly occurs. Symptoms of potassium deficiency in white spruce include: browning and death of needles (chlorosis); reduced growth in height and diameter; impaired retention of needles; and reduced needle length. [ 43 ]


Mo deficiency is usually found on older growth. Fe, Mn and  Cu effect new growth, causing green or yellow veins, Zn ca effect old and new leaves, and B will be seem on terminal buds. A plant with  zinc deficiency  may have leaves on top of each other due to reduced internodal expansion. [ 44 ]


Zinc is the most widely deficient micronutrient for industrial crop cultivation, followed by boron. Acidifying N fertilizers create micro-sites around the  granule  that keep micronutrient cations soluble for longer in alkaline soils, but high concentrations of P or C may negate these effects.


Boron deficiencies effecting seed yields and pollen fertility are common in  laterite soils . [ 45 ]  Boron is essential for the proper forming and strengthening of cell walls. Lack of boron results in short thick cells producing stunted fruiting bodies and roots. Deficiency results in the death of the terminal growing points and stunted growth. [ citation needed ]  Inadequate amounts of boron affect many agricultural crops, legume forage crops most strongly. [ citation needed ]  Boron deficiencies can be detected by analysis of plant material to apply a correction before the obvious symptoms appear, after which it is too late to prevent crop loss. Strawberries deficient in boron will produce lumpy fruit; apricots will not blossom or, if they do, will not fruit or will drop their fruit depending on the level of boron deficit. Broadcast of boron supplements is effective and long term; a foliar spray is immediate but must be repeated. [ citation needed ]


Boron concentration in soil water solution higher than one ppm is toxic to most plants. Toxic concentrations within plants are 10 to 50 ppm for small grains and 200 ppm in boron-tolerant crops such as sugar beets, rutabaga, cucumbers, and conifers. Toxic soil conditions are generally limited to arid regions or can be caused by underground borax deposits in contact with water or volcanic gases dissolved in percolating water. [ citation needed ]


There is an abundant supply of nitrogen in the earth's atmosphere—N 2  gas comprises nearly 79% of air. However, N 2  is unavailable for use by most organisms because there is a triple bond between the two nitrogen atoms in the molecule,  making it almost inert. In order for nitrogen to be used for growth it must be  "fixed"  (combined) in the form of  ammonium  (NH + 4 ) or nitrate (NO − 3 ) ions. The weathering of rocks releases these ions so slowly that it has a negligible effect on the availability of fixed nitrogen. Therefore, nitrogen is often the limiting factor for growth and  biomass  production in all environments where there is a suitable climate and availability of water to support life.


Microorganisms  have a central role in almost all aspects of nitrogen availability, and therefore for life support on earth. Some bacteria can convert N 2  into ammonia by the process termed  nitrogen fixation ; these bacteria are either free-living or form  symbiotic  associations with plants or other organisms (e.g., termites, protozoa), while other bacteria bring about transformations of  ammonia  to  nitrate , and of nitrate to N 2  or other nitrogen gases. Many  bacteria  and  fungi  degrade organic matter, releasing fixed nitrogen for reuse by other organisms. All these processes contribute to the  nitrogen cycle .


Nitrogen enters the plant largely through the  roots . A "pool" of soluble nitrogen accumulates. Its composition within a species varies widely depending on several factors, including day length, time of day, night temperatures, nutrient deficiencies, and nutrient imbalance. Short day length promotes  asparagine  formation, whereas glutamine is produced under long day regimes. Darkness favors protein breakdown accompanied by high asparagine accumulation. Night temperature modifies the effects due to night length, and soluble nitrogen tends to accumulate owing to retarded synthesis and breakdown of proteins. Low night temperature conserves  glutamine ; high night temperature increases accumulation of asparagine because of breakdown. Deficiency of K accentuates differences between long- and short-day plants. The pool of soluble nitrogen is much smaller than in well-nourished plants when N and P are deficient since uptake of nitrate and further reduction and conversion of N to organic forms is restricted more than is protein synthesis. Deficiencies of Ca, K, and S affect the conversion of organic N to protein more than uptake and reduction. The size of the pool of soluble N is no guide  per se  to growth rate, but the size of the pool in relation to total N might be a useful ratio in this regard. Nitrogen availability in the rooting medium also affects the size and structure of tracheids formed in the long lateral roots of white spruce (Krasowski and Owens 1999). [ 46 ]


Phosphorus is most commonly found in the soil in the form of polyprotic phosphoric acid (H 3 PO 4 ), but is taken up most readily in the form of H 2 PO − 4 . Phosphorus is available to plants in limited quantities in most soils because it is released very slowly from insoluble phosphates and is rapidly fixed once again. Under most environmental conditions it is the element that limits growth because of this constriction and due to its high demand by plants and microorganisms. Plants can increase phosphorus uptake by a mutualism with mycorrhiza. [ 6 ]  On some  soils , the phosphorus nutrition of some  conifers , including the spruces, depends on the ability of  mycorrhizae  to take up, and make soil phosphorus available to the tree, hitherto unobtainable to the non-mycorrhizal root. Seedling white spruce, greenhouse-grown in sand testing negative for phosphorus, were very small and purple for many months until spontaneous mycorrhizal inoculation, the effect of which was manifested by a greening of foliage and the development of vigorous shoot growth.


When  soil -potassium levels are high, plants take up more potassium than needed for healthy growth. The term  luxury consumption  has been applied to this. Potassium intake increases with root temperature and depresses calcium uptake. [ 47 ]  Calcium to boron ratio must be maintained in a narrow range for normal plant growth. Lack of boron causes failure of calcium metabolism which produces hollow heart in beets and peanuts. [ citation needed ]


Calcium and magnesium inhibit the uptake of trace metals. Copper and zinc mutually reduce uptake of each other. Zinc also effects iron levels of plants. These interactions are dependent on species and growing conditions. For example, for clover, lettuce and red beet plants nearing toxic levels of zinc, copper and nickel, these three elements increased the toxicity of the others in a positive relationship. In barley positive interaction was observed between copper and zinc, while in French beans the positive interaction occurred between nickel and zinc. Other researchers have studied the synergistic and antagonistic effects of soil conditions on lead, zinc, cadmium and copper in radish plants to develop predictive indicators for uptake like  soil pH . [ 48 ]


Calcium absorption is increased by water-soluble phosphate fertilizers, and is used when potassium and  potash  fertilizers decrease the uptake of phosphorus, magnesium and calcium. For these reasons, imbalanced application of potassium fertilizers can markedly decrease crop yields. [ 39 ]


Boron  is available to plants over a range of pH, from 5.0 to 7.5. Boron is absorbed by plants in the form of the anion BO 3− 3 . It is available to plants in moderately soluble mineral forms of Ca, Mg and Na borates and the highly soluble form of organic compounds. It is mobile in the soil, hence, it is prone to leaching. Leaching removes substantial amounts of boron in sandy soil, but little in fine silt or clay soil. Boron's fixation to those minerals at high pH can render boron unavailable, while low pH frees the fixed boron, leaving it prone to leaching in wet climates. It precipitates with other minerals in the form of borax in which form it was first used over 400 years ago as a soil supplement. Decomposition of organic material causes boron to be deposited in the topmost soil layer. When soil dries it can cause a precipitous drop in the availability of boron to plants as the plants cannot draw nutrients from that desiccated layer. Hence, boron deficiency diseases appear in dry weather. [ citation needed ]


Most of the nitrogen taken up by plants is from the soil in the forms of NO − 3 , although in acid environments such as boreal forests where nitrification is less likely to occur, ammonium NH + 4  is more likely to be the dominating source of nitrogen. [ 49 ]  Amino acids and proteins can only be built from NH + 4 , so NO − 3  must be reduced.


Fe and Mn become oxidized and are highly unavailable in acidic soils. [ citation needed ]


Nutrient status (mineral nutrient and trace element composition, also called ionome and nutrient profile) of plants are commonly portrayed by tissue elementary analysis. Interpretation of the results of such studies, however, has been controversial. [ 50 ]  During recent decades the nearly two-century-old "law of minimum" or "Liebig's law" (that states that plant growth is controlled not by the total amount of resources available, but by the scarcest resource) has been replaced by several mathematical approaches that use different models in order to take the interactions between the individual nutrients into account. [ citation needed ]


Later developments in this field were based on the fact that the nutrient elements (and compounds) do not act independently from each other; [ 50 ]  Baxter, 2015, [ 51 ]  because there may be direct chemical interactions between them or they may influence each other's uptake, translocation, and biological action via a number of mechanisms [ 50 ]  as exemplified [ how? ]  for the case of ammonia. [ 52 ]


Boron is highly soluble in the form of borax or boric acid and is too easily leached from soil making these forms unsuitable for use as a fertilizer. Calcium borate is less soluble and can be made from  sodium tetraborate . Boron is often applied to fields as a contaminant in other soil amendments but is not generally adequate to make up the rate of loss by cropping. The rates of application of borate to produce an adequate alfalfa crop range from 15 pounds per acre for a sandy-silt, acidic soil of low organic matter, to 60 pounds per acre for a soil with high organic matter, high cation exchange capacity and high pH. Application rates should be limited to a few pounds per acre in a test plot to determine if boron is needed generally. Otherwise, testing for boron levels in plant material is required to determine remedies. Excess boron can be removed by irrigation and assisted by application of elemental sulfur to lower the pH and increase boron solubility. Foliar sprays are used on fruit crop trees in soils of high alkalinity. [ citation needed ]


Selenium is, however, an essential mineral element for animal (including human) nutrition and  selenium deficiencies  are known to occur when food or animal feed is grown on selenium-deficient soils. The use of inorganic selenium fertilizers can increase selenium concentrations in edible crops and animal diets thereby improving animal health. [ 31 ]


It is useful to apply a high phosphorus content fertilizer, such as bone meal, to perennials to help with successful root formation. [ 6 ]


Hydroponics  is a method for growing plants in a water-nutrient solution without using nutrient-rich soil or substrates. Researchers and home gardeners can grow their plants in a controlled environment. The most common artificial nutrient solution is the  Hoagland solution , developed by D. R. Hoagland and W. C. Snyder in 1933. The solution (known as  A-Z solution ) consists of all the essential macro- and micronutrients in the correct proportions necessary for most plant growth. [ 6 ]  An aerator is used to prevent an  anoxic  event or hypoxia.  Hypoxia  can affect the nutrient uptake of a plant because, without oxygen present, respiration becomes inhibited within the root cells. The  nutrient film technique  is a hydroponic technique in which the roots are not fully submerged. Incomplete submergence allows for adequate aeration of the roots, while a "film" thin layer of nutrient-rich water is pumped through the system to provide nutrients and water to the plant.


Potassium  is the main  intracellular   ion  for all types of  cells , while having a major role in maintenance of  fluid  and  electrolyte  balance. [ 1 ] [ 2 ]  Potassium is necessary for the function of all living cells and is thus present in all plant and animal tissues. It is found in especially high concentrations within plant cells, and in a mixed diet, it is most highly concentrated in fruits. The high concentration of potassium in plants, associated with comparatively very low amounts of sodium there, historically resulted in potassium first being isolated from the ashes of plants ( potash ), which in turn gave the element its modern name. The high concentration of potassium in plants means that heavy crop production rapidly depletes soils of potassium, and agricultural fertilizers consume 93% of the potassium chemical production of the modern world economy.


The functions of potassium and sodium in living organisms are quite different. Animals, in particular, employ sodium and potassium differentially to generate electrical potentials in animal cells, especially in  nervous tissue . Potassium depletion in animals, including humans, results in various neurological dysfunctions. Characteristic concentrations of potassium in model organisms are: 30–300 mM in  E. coli , 300 mM in budding yeast, 100 mM in mammalian cell and 4 mM in blood plasma. [ 3 ]


The main role of potassium in plants is to provide the ionic environment for metabolic processes in the  cytosol , and as such functions as a regulator of various processes including growth regulation. [ 4 ]  Plants require potassium  ions  (K + ) for  protein synthesis  and for the opening and closing of  stomata , which is regulated by  proton pumps  to make surrounding guard cells either  turgid  or  flaccid .  A deficiency of potassium ions can impair a plant's ability to maintain these processes. Potassium also functions in other physiological processes such as  photosynthesis ,  protein synthesis , activation of some  enzymes , phloem solute transport of photoassimilates into  source organs , and maintenance of cation:anion balance in the cytosol and  vacuole . [ 5 ]


Potassium is the major  cation  (K + , a positive ion) inside  animal cells , while  sodium  (Na + ) is the major cation outside animal cells. The difference between the  concentrations  of these charged particles causes a difference in  electric potential  between the inside and outside of cells, known as the  membrane potential .  The balance between potassium and sodium is maintained by  ion transporters  in the  cell membrane . All  potassium ion channels  are tetramers with several conserved secondary structural elements. A number of potassium channel structures have been  solved  including  voltage gated , [ 6 ] [ 7 ] [ 8 ]   ligand gated , [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]   tandem-pore , [ 14 ] [ 15 ] [ 16 ]  and  inwardly rectifying  channels, [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ]  from  prokaryotes  and  eukaryotes . The cell membrane potential created by potassium and sodium  ions allows the cell to generate an  action potential —a "spike" of electrical discharge. The ability of cells to produce electrical discharge is critical for body functions such as  neurotransmission , muscle contraction, and heart function. [ 22 ]


The U.S.  National Academy of Medicine  (NAM), on behalf of both the U.S. and Canada, sets  Dietary Reference Intakes , including Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs), or  Adequate Intakes  (AIs) for when there is not sufficient information to set EARs and RDAs.


For both males and females under 9 years of age, the AIs for potassium are: 400   mg of potassium for 0 to 6-month-old infants, 860   mg of potassium for 7 to 12-month-old infants, 2,000   mg of potassium for 1 to 3-year-old children, and 2,300   mg of potassium for 4 to 8-year-old children.


For males 9 years of age and older, the AIs for potassium are: 2,500   mg of potassium for 9 to 13-year-old males, 3,000   mg of potassium for 14 to 18-year-old males, and 3,400   mg for males that are 19 years of age and older.


For females 9 years of age and older, the AIs for potassium are: 2,300   mg of potassium for 9 to 18-year-old females, and 2,600   mg of potassium for females that are 19 years of age and older.


For pregnant and lactating females, the AIs for potassium are: 2,600   mg of potassium for 14 to 18-year-old pregnant females, 2,900   mg for pregnant females that are 19 years of age and older; furthermore, 2,500   mg of potassium for 14 to 18-year-old lactating females, and 2,800   mg for lactating females that are 19 years of age and older. As for safety, the NAM also sets  tolerable upper intake levels  (ULs) for vitamins and minerals, but for potassium the evidence was insufficient, so no UL was established. [ 23 ] [ 24 ]


In 2019, the  National Academies of Sciences, Engineering, and Medicine  revised the Adequate Intake for potassium to 2,600 mg/day for females 19 years of age and older who are not pregnant or lactating, and 3,400 mg/day for males 19 years of age and older. [ 25 ] [ 26 ]


The  European Food Safety Authority  (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the United States. For people ages 15 and older, the AI is set at 3,500 mg/day. AIs for pregnancy is 3,500 mg/day, for lactation 4,000 mg/day. For children ages 1–14 years, the AIs increase with age from 800 to 2,700 mg/day. These AIs are lower than the U.S. RDAs. [ 27 ]  The EFSA reviewed the same safety question and decided that there was insufficient data to establish a UL for potassium. [ 28 ]


For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For potassium labeling purposes, 100% of the Daily Value was 3500 mg, but as of May 2016, it has been revised to 4700 mg. [ 29 ] [ 30 ]  A table of the old and new adult Daily Values is provided at  Reference Daily Intake .


20 mEq (781 mg) potassium from  potassium gluconate  (4680 mg), or  potassium citrate  (2040 mg), mixed with a half-cup (1.12 dL) water, taken two to four times a day, may be used on a daily basis. [ 31 ] [ 32 ]


Because of the risk of small-bowel lesions, the US  FDA  requires some potassium  salts  (for example  potassium chloride ) containing more than 99 mg (about 1.3 mEq) to be labeled with a warning. [ 33 ]


Eating a variety of foods that contain potassium is the best way to get an adequate amount.
Foods with high sources of potassium include  kiwifruit ,  orange juice ,  potatoes ,  coconut ,  avocados ,  apricots ,  parsnips  and  turnips , although many other  fruits ,  vegetables , legumes, and meats contain potassium.


Common foods very high in potassium: [ 34 ]


Foods containing the highest concentration: [ 34 ]


Diets low in potassium increase risk of hypertension, stroke and cardiovascular disease. [ 36 ] [ 37 ]


A severe shortage of potassium in body fluids may cause a potentially fatal condition known as  hypokalemia .  Hypokalemia typically results from loss of potassium through   diarrhea ,  diuresis , or vomiting. Symptoms are related to alterations in  membrane potential and cellular metabolism.  Symptoms include muscle weakness and cramps, paralytic  ileus , ECG abnormalities, intestinal paralysis, decreased reflex response and (in severe cases) respiratory paralysis,  alkalosis  and  arrhythmia .


In rare cases, habitual consumption of large amounts of black licorice has resulted in hypokalemia. Licorice contains a compound ( Glycyrrhizin ) that increases urinary excretion of potassium. [ 38 ]


Adult women in the United States consume on average half the AI, for men two-thirds. For all adults, fewer than 5% exceed the AI. [ 39 ]  Similarly, in the  European Union , insufficient potassium intake is widespread. [ 40 ]


Gastrointestinal  symptoms are the most common side effects of potassium supplements, including nausea, vomiting, abdominal discomfort, and diarrhea.  Taking potassium with meals or taking a  microencapsulated form of potassium may reduce gastrointestinal side effects.


Hyperkalemia  is the most serious adverse reaction to potassium.  Hyperkalemia occurs when potassium builds up faster than the kidneys can remove it. It is most common in individuals with  renal failure .  Symptoms of hyperkalemia may include tingling of the hands and feet, muscular weakness, and temporary paralysis. The most serious complication of hyperkalemia is the development of an abnormal heart rhythm ( arrhythmia ), which can lead to cardiac arrest.


Although hyperkalemia is rare in healthy individuals, oral doses greater than 18 grams taken at one time in individuals not accustomed to high intakes can lead to hyperkalemia.


Selenium  is an essential  micronutrient  for animals, though it is toxic in large doses. In plants, it sometimes occurs in toxic amounts as  forage , e.g.  locoweed . Selenium is a component of the  amino acids   selenocysteine  and  selenomethionine . In humans, selenium is a  trace element  nutrient that functions as  cofactor  for  glutathione peroxidases  and certain forms of  thioredoxin reductase . [ 1 ]  Selenium-containing proteins are produced from inorganic selenium via the intermediacy of  selenophosphate  (PSeO 3 3− ).


Selenium is an essential  micronutrient  in mammals, but is also recognized as toxic in excess. Selenium exerts its biological functions through  selenoproteins , which contain the  amino acid   selenocysteine . Twenty-five selenoproteins are encoded in the  human genome . [ 2 ]


The  glutathione peroxidase  family of enzymes (abbreviated GSH-Px) catalyze reduction of  hydrogen peroxide  and organic  hydroperoxides :


The two H atoms are donated by thiols in a process that begins with oxidation of a  selenol  side chain in GSH-Px.  The  organoselenium compound   ebselen  is a drug used to supplement the action of GSH-Px.  It functions as a catalyst for the destruction of hydrogen peroxide. [ 3 ]


A related selenium-containing enzyme in some plants and in animals ( thioredoxin reductase ) generates reduced thioredoxin, a dithiol that serves as an electron source for peroxidases and also the important reducing enzyme  ribonucleotide reductase  that makes DNA precursors from RNA precursors. [ 4 ]


Selenium also plays a role in the functioning of the  thyroid  gland.  It participates as a  cofactor  for the three  thyroid hormone   deiodinases .  These enzymes activate and then deactivate various thyroid hormones and their metabolites. [ 5 ]  It may inhibit  Hashimoto's disease , an auto-immune disease in which the body's own thyroid cells are attacked by the immune system. A reduction of 21% on TPO antibodies was reported with the dietary intake of 0.2 mg of selenium. [ 6 ]


Some microorganisms utilize selenium in  formate dehydrogenase . Formate is produced in large amounts in the hepatic (liver cells) mitochondria of embryonic cells and in cancer cells by the folate cycle. [ 7 ]


Formate is reversibly oxidized by the enzyme  formate dehydrogenase : [ 8 ]


Thioredoxin reductase  uses a cysteine-selenocysteine pair to reduce the  disulfide  in  thioredoxin . The selenocysteine  is arranged in an unusual Sec-His-Glu  catalytic triad , which tunes its pKa. [ 9 ]


Certain species of plants are considered indicators of high selenium content of the soil, since they require high levels of selenium to thrive. The main selenium indicator plants are  Astragalus  species (including some  locoweeds ), prince's plume ( Stanleya  sp.), woody asters ( Xylorhiza  sp.), and false goldenweed ( Oonopsis  sp.) [ 10 ]


The substance loosely called  selenium sulfide  (with the approximate formula SeS 2 ) is the active ingredient in some anti-dandruff shampoos. [ 11 ]  The selenium compound kills the scalp fungus  Malassezia , which causes shedding of dry skin fragments. The ingredient is also used in body lotions to treat  Tinea versicolor  due to infection by a different species of  Malassezia  fungus. [ 12 ]


Several clinical trials have assessed the use of selenium supplements in critically ill adults; however, the effectiveness and potential benefits of selenium supplementation in this context is not well understood. [ 13 ]


Selenium may be measured in blood, plasma, serum or urine to monitor excessive environmental or occupational exposure, confirm a diagnosis of poisoning in hospitalized victims or to assist in a forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body prior to being eliminated in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations. [ 14 ]


Although selenium is an essential  trace element , it is toxic if taken in excess. Exceeding the  Tolerable Upper Intake Level  of 400 micrograms per day can lead to selenosis. [ 15 ]  This 400 microgram ( μg ) Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow-up study on the same five people in 1992. [ 16 ]  The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to not only avoid  toxicity , but also to avoid creating an imbalance of nutrients in the diet and to account for data from other countries. [ 17 ]  In China, people who  ingested corn grown in extremely selenium-rich stony coal (carbonaceous  shale ) have suffered from selenium toxicity. This coal was shown to have selenium content as high as 9.1%, the highest concentration in coal ever recorded in literature. [ 18 ]


Symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, sloughing of nails, fatigue, irritability, and neurological damage. Extreme cases of selenosis can result in  cirrhosis  of the liver,  pulmonary edema , and death. [ 19 ]  Elemental selenium and most metallic  selenides  have relatively low toxicities because of their low  bioavailability . By contrast,  selenates  and  selenites  are very toxic, having an oxidant mode of action similar to that of arsenic trioxide. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day for a long time. [ 20 ]   Hydrogen selenide  is an extremely toxic, corrosive gas. [ 21 ]  Selenium also occurs in organic compounds, such as dimethyl selenide,  selenomethionine ,  selenocysteine  and  methylselenocysteine , all of which have high  bioavailability  and are toxic in large doses.


Selenium poisoning  of water systems may result whenever new agricultural runoff courses through normally dry, undeveloped lands. This process leaches natural soluble selenium compounds (such as selenates) into the water, which may then be concentrated in new "wetlands" as the water evaporates. High selenium levels produced in this fashion have been found to have caused certain congenital disorders in wetland birds. [ 22 ]


In fish and other wildlife, low levels of selenium cause deficiency while high levels cause toxicity.  For example, in salmon, the optimal concentration of selenium in the fish tissue (whole body) is about 1 microgram selenium per gram of tissue (dry weight).  At levels much below that concentration, young salmon die from selenium deficiency; [ 23 ]  much above that level they die from toxic excess. [ 24 ]


Selenium deficiency can occur in patients with severely compromised  intestinal  function, those undergoing  total parenteral nutrition , and [ 25 ]  in those of advanced age (over 90). Also, people dependent on food grown from selenium-deficient soil are at risk. Although  New Zealand  has low levels of selenium in its soil, adverse health effects have not been detected. [ 26 ]


Selenium deficiency as defined by low (<60% of normal) selenoenzyme activity levels in brain and endocrine tissues only occurs when a low selenium status is linked with an additional stress, such as high exposures to mercury [ 27 ]  or as a result of increased oxidant stress due to vitamin E deficiency. [ 28 ]


Selenium interacts with other nutrients, such as  iodide  and  vitamin E . The interaction is observed in the  etiology  of many deficiency diseases in animals, and pure selenium deficiency is rare. The effect of selenium deficiency on health remains uncertain, particularly in relation to  Kashin-Beck disease . [ 29 ]


The US Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for selenium in 2000. If there is not sufficient information to establish EARs and RDAs, an estimate designated  Adequate Intake  (AI) is used instead. The current EAR for selenium for people ages 14 and up is 45 μg/day. The RDA is 55 μg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher-than-average requirements. RDA for pregnancy is 60 μg/day. RDA for lactation is 70 μg/day. For children ages 1–13 years, the RDA increases with age from 20 to 40 μg/day. As for safety, the IOM sets  Tolerable upper intake levels  (ULs) for vitamins and minerals when evidence is sufficient. In the case of selenium, the UL is 400 μg/day. Collectively the EARs, RDAs, AIs and ULs are referred to as  Dietary Reference Intakes  (DRIs). [ 30 ]


The  European Food Safety Authority  (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the United States. For women and men ages 15 and older, the AI is set at 70 μg/day. AI for pregnancy is 70 μg/day; for lactation, 85 μg/day. For children ages 1–14 years, the AIs increase with age from 15 to 55 μg/day. These AIs are higher than the U.S. RDAs. [ 31 ]  The European Food Safety Authority reviewed the same safety question and set its UL at 300 μg/day, which is lower than the U.S. value. [ 32 ]


In the United States, selenium deficiency is not common. A federal survey of food consumption determined that for women and men over the age of 19, average consumption from foods and beverages was 89 and 125 μg/day, respectively. For women and men of all ages fewer than 3% consumed less than the EAR. [ 33 ]


For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For selenium labeling purposes, 100% of the Daily Value was 70 μg, but as of 27 May 2016 it was revised to 55 μg. [ 34 ] [ 35 ]  A table of the old and new adult daily values is provided at  Reference Daily Intake .


Dietary selenium comes from nuts,  cereals ,  meat ,  mushrooms ,  fish , and  eggs .  Brazil nuts  are the richest ordinary dietary source and could cause selenium toxicity if consumed regularly – though the actual concentration of selenium (as with any plant-based food sources, such as another selenium-accumulating "paradise nut"  Lecythis , belonging to the same family  Lecythidaceae ) is soil-dependent and may vary significantly by geographic location. In descending order of concentration, high levels are also found in  kidney ,  tuna ,  crab , and  lobster . [ 36 ] [ 37 ]


The human body's content of selenium is believed to be in the 13–20 milligram range. [ 38 ]


Selenium  has bimodal biological action depending on the concentration. At low nutritional doses, selenium acts as an  antioxidant  through  selenoproteins , scavenging  ROS , supporting cell survival and growth; while, at supra-nutritional higher pharmacological doses, selenium acts as a  pro-oxidant  generating  ROS  and inducing  cell death . In cancer, studies have been conducted mostly on the benefits of selenium intake in reducing the risk of cancer incidence at the nutritional level; however, fewer studies have explored the effects of supra-nutritional or pharmacological doses of selenium on cancer. [ 39 ]


"Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution... Conflicting results including inverse, null and direct associations have been reported for some cancer types... RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results... To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans." [ 40 ]


To date, many studies have been conducted on the benefits of selenium intake in reducing the risk of  cancer incidence  at the nutritional level, indicating that likely selenium functions as an  immunostimulator , i.e. reversing the  immunosuppression  in  tumour microenvironment  towards antitumour  immunity  by activating  immune cells  (e.g.  M1 macrophages  and  CD8+ T-lymphocytes , the elevated number of  neutrophils  and activated cytotoxic  NK cells ) and releasing  pro-inflammatory   cytokines  such as  IFNγ  and  TNFα . [ 39 ]


AIDS appears to involve a slow and progressive decline in levels of selenium in the body. Whether this decline in selenium levels is a direct result of the replication of HIV or related more generally to the overall malabsorption of nutrients by AIDS patients remains debated. Observational studies have found an association between decreased selenium levels and poorer outcomes in patients with HIV, though these studies were mostly done prior to the currently effective treatments with highly active antiretroviral therapy ( HAART ).  Currently there is inadequate evidence to recommend routine selenium supplementation for HIV patients, and further research is recommended. [ 41 ]


Selenium supplementation has no effect on overall mortality. [ 42 ]


As with other types of supplementation, there is no good evidence selenium supplementation helps in the treatment of tuberculosis. [ 43 ]


A meta-analysis of four RCTs concluded that there is no support for selenium supplementation for prevention of type 2 diabetes mellitus in Caucasians. [ 44 ]


Abnormally high or low levels of dietary selenium can have an adverse effect on sperm quality, with a consequent lowering of fertility. [ 45 ]


During the COVID-19 pandemic, some studies attempted to establish a correlation between selenium plasma level and severity of COVID-19 cases. One study done on 33 patients concluded that low plasma selenium levels were correlated with a high mortality rate among COVID-19 patients. However, the median age of deaths in this study was 89 years old; in contrast, survivors' median age was 69 years old, and the study stated that the causality remains unknown. [ 46 ]
On the other hand, another study revealed that the mean selenium plasma level was within the normal range among all included COVID-19 patients; however, the mean selenium plasma level was elevated among severe cases of COVID-19. This study concluded that there was a significant elevation of selenium serum level among severe cases compared to non-severe cases of COVID-19, and could be correlated with the disease severity. [ 47 ]


Selenium has a protective effect towards mercury toxicity. Mercury binds to selenium with high affinity, so this metal can inhibit selenium-dependent enzymes. However, increased selenium intake can preserve the enzyme activities, reducing the adverse effects caused by mercury exposure. [ 48 ]   [ 49 ]


Selenium is incorporated into several prokaryotic selenoprotein families in bacteria, archaea, and eukaryotes as selenocysteine, [ 50 ]  where selenoprotein peroxiredoxins protect bacterial and eukaryotic cells against oxidative damage. Selenoprotein families of GSH-Px and the deiodinases of eukaryotic cells seem to have a bacterial  phylogenetic  origin. The selenocysteine-containing form occurs in species as diverse as green algae, diatoms, sea urchin, fish and chicken. Selenium enzymes are involved in utilization of the small reducing molecules  glutathione  and  thioredoxin .


Trace elements involved in GSH-Px and superoxide dismutase enzymes activities, i.e. selenium,  vanadium ,  magnesium ,  copper , and  zinc , may have been lacking in some terrestrial mineral-deficient areas. [ 50 ]  Marine organisms retained and sometimes expanded their seleno-proteomes, whereas the seleno-proteomes of some terrestrial organisms were reduced or completely lost. These findings suggest that aquatic life supports selenium utilization, whereas terrestrial habitats lead to reduced use of this trace element. [ 51 ] [ 52 ]  Marine fishes and vertebrate thyroid glands have the highest concentration of selenium and iodine. From about 500 Mya, freshwater and terrestrial plants slowly optimized the production of "new" endogenous antioxidants such as  ascorbic acid  (Vitamin C),  polyphenols  (including flavonoids),  tocopherols , etc. A few of these appeared more recently, in the last 50–200 million years, in fruits and flowers of angiosperm plants. In fact, the angiosperms (the dominant type of plant today) and most of their antioxidant pigments evolved during the late  Jurassic  period.


About 200 Mya, new selenoproteins were developed as mammalian GSH-Px enzymes. [ 53 ] [ 54 ] [ 55 ] [ 56 ]


Selenium yeast  is a  feed additive  for livestock, used to increase the  selenium  content in their  fodder . It is a form of selenium currently approved for human consumption in the EU and Britain. [ 1 ]  Inorganic forms of selenium are used in feeds (namely  sodium selenate  and  sodium selenite , which appear to work in roughly the same manner). Since these products can be patented, producers can demand premium prices. [ 2 ]  It is produced by fermenting  Saccharomyces cerevisiae  (baker's yeast) in a selenium-rich media. [ 3 ]


There is considerable variability in products described as Se-yeast and the selenium compounds found within. Many manufacturers and products on the market are simply mixtures of largely inorganic selenium and some yeast. [ 4 ]  Selenium is found in different forms based upon the food in which it is found. For instance, the form found in mustard and garlic is different from the form found in wheat or corn. In some products, the added selenium is structurally substituted for sulfur in the amino acid  methionine , thus forming an  organic chemical  called  selenomethionine  via the same pathways and enzymes. Owing to its similarity to sulfur-containing methionine, selenomethionine is mistaken for an  amino acid  by the yeast anabolism and incorporated in its proteins. It has been claimed that selenomethionine makes a better source of dietary selenium in animal nutrition, since it is an organic chemical compound sometimes found in some common crops such as wheat. [ 3 ] [ 5 ]


Large amounts of  selenium are toxic ; however, it is physiologically necessary for animals in extremely small amounts. Many other uncharacterized selenium-containing organic chemicals are also produced by a method similar to that of selenomethionine; some have recently been characterized but remain relatively unknown, such as  S -seleno-methyl-glutathione and glutathione- S -selenoglutathione. [ 3 ] [ 4 ]  Due to this, the European Union has questioned the safety and potential toxicity of this food supplement for humans, and it may not be used as an additive after 2002.


G.N Schrauzer , who has written two papers about selenomethionine, claims it should be an  essential amino acid , and that the product is completely safe. [ 3 ]  The  European Food Safety Authority  does allow the use of selenomethionine as a feed additive for animals. [ 6 ]  Because organic forms of selenium appear to be excreted from the body slower than inorganic forms, products enriched with organic selenium might detrimentally  bioaccumulate  in the body. Because selenium-enriched foods contain much more selenium than natural foods, selenium toxicity is a potential problem, and such foods must be treated with caution. [ 4 ]  The EU allows up to 300 micrograms of selenium per day, but one long-term study of selenium supplementation showed no evidence of toxicity at a dose as high as 800 micrograms per day. [ 7 ]


An organic selenium-containing chemical found in selenium yeast has been shown to differ in bioavailability and metabolism compared with common inorganic forms of dietary selenium. [ 8 ]  Dietary supplementation using selenium yeast is ineffective in the production of antioxidants in bovine milk compared to inorganic selenium (sodium selenate). [ 9 ]  One study examined if increased selenium in the diet of mutant mice (via a selenium yeast product) caused a higher production of selenium-containing enzymes which have an antioxidant effect. The effect was modest. [ 10 ]


Selenium supplementation in yeast form has been shown to increase pig selenium-containing antioxidant enzymes, [ 11 ]  broiler growth and meat quality, [ 12 ] [ 13 ]  the shelf life of turkey and rooster semen, [ 14 ] [ 15 ] [ 16 ]  and possibly cattle fertility. [ 17 ]


Selenium supplementation in animal feeds may be profitable for agribusinesses. It may be possible to market selenium-fortified foods to consumers as  functional foods , such as selenium-enriched eggs, meat, [ 18 ] [ 19 ] [ 20 ] [ 21 ]  or milk. [ 9 ]


A patented cultivar of yeast ( Saccharomyces cerevisiae  'CNCM I-3060') marketed as Sel-Plex® has been approved for use in animal  fodder :


Total selenium in selenium yeast can be reliably determined using open acid digestion to extract selenium from the yeast matrix followed by flame atomic absorption spectrometry. [ 24 ]  Determination of the selenium species selenomethionine can be achieved via proteolytic digestion of selenium yeast followed by high-performance liquid chromatography with inductively coupled plasma mass spectrometry. [ 25 ] [ 26 ] [ 27 ]


Nutritional muscular dystrophy


Sodium ions ( Na + ) are necessary in small amounts for some types of  plants , [ 1 ]  but  sodium  as a nutrient is more generally needed in larger amounts [ 1 ]  by  animals , due to their use of it for generation of  nerve impulses  and for maintenance of  electrolyte  balance and  fluid balance . In animals, sodium ions are necessary for the aforementioned functions and for  heart  activity and certain  metabolic  functions. [ 2 ]  The  health effects of salt  reflect what happens when the body has too much or too little sodium.
Characteristic concentrations of  sodium  in model organisms are: 10  mM  in  E. coli , 30 mM in budding yeast, 10 mM in mammalian cell and 100 mM in blood plasma. [ 3 ]


Additionally, sodium ions are essential to several cellular processes. They are responsible for the co-transport of glucose in the sodium glucose symport, are used to help maintain membrane polarity with the help of the sodium potassium pump, and are paired with water to thin the mucus of the airway lumen when the active Cystic Fibrosis Transport Receptor moves chloride ions into the airway. [ 4 ]


The minimum physiological requirement for sodium is between 115 and 500 mg per day depending on sweating due to physical activity, and whether the person is adapted to the climate. [ 5 ]   Sodium chloride  is the principal source of sodium in the diet, and is used as seasoning and preservative, such as for  pickling  and  jerky ; most of it comes from processed foods. [ 6 ]  The  Adequate Intake  for sodium is 1.2 to 1.5 g per day, [ 7 ]  but on average people in the United States consume  3.4 g per day, [ 8 ] [ 9 ]  the minimum amount that promotes hypertension. [ 10 ]  Note that salt contains about 39.3% sodium by mass [ 11 ] —the rest being chlorine and other trace chemicals; thus the  Tolerable Upper Intake Level  of 2.3 g sodium would be about 5.9 g of salt—about 1  teaspoon . [ 12 ]  The average daily excretion of sodium is between 40 and 220 mEq. [ 13 ]


Normal serum sodium levels are between approximately 135 and 145  mEq /L (135 to 145 mmol/L). A serum sodium level of less than 135 mEq/L qualifies as  hyponatremia , which is considered severe when the serum sodium level is below 125 mEq/L. [ 14 ] [ 15 ]


The  renin–angiotensin system  and the  atrial natriuretic peptide  indirectly regulate the amount of  signal transduction  in the human  central nervous system , which depends on sodium ion motion across the nerve cell membrane, in all nerves. Sodium is thus important in  neuron  function and osmoregulation between cells and the  extracellular fluid ; the distribution of sodium ions are mediated in all animals by  sodium–potassium pumps , which are active transporter  solute pumps , pumping ions against the gradient, and sodium-potassium channels. [ 16 ]  Sodium channels are known to be less selective in comparison to potassium channels. Sodium is the most prominent cation in extracellular fluid: in the 15 L of  extracellular fluid  in a 70 kg human there is around 50 grams of sodium, 90% of the body's total sodium content.


Some potent  neurotoxins , such as  batrachotoxin , increase the sodium ion permeability of the  cell membranes  in nerves and muscles, causing a massive and irreversible  depolarization  of the membranes with potentially fatal consequences. However, drugs with smaller effects on sodium ion motion in nerves may have diverse pharmacological effects that range from anti-depressant to anti-seizure actions.


Since only some plants need sodium and those in small quantities, a completely  plant-based diet  will generally be very low in sodium. [ citation needed ]  This requires some herbivores to obtain their sodium from  salt licks  and other mineral sources. The animal need for sodium is probably the reason for the highly conserved ability to  taste  the sodium ion as "salty." Receptors for the pure salty taste respond best to sodium; otherwise, the receptors respond only to a few other small monovalent cations ( Li + ,  NH + 4  and somewhat to  K + ). The  calcium  ion (Ca 2+ ) also tastes salty and sometimes bitter to some people but, like potassium, can trigger other tastes.


Sodium ions play a diverse and important role in many physiological processes, acting to regulate  blood volume ,  blood pressure ,  osmotic equilibrium  and  pH . [ 8 ]


In  C4 plants , sodium is a  micronutrient  that aids in metabolism, specifically in regeneration of  phosphoenolpyruvate  (involved in the biosynthesis of various aromatic compounds, and in  carbon fixation ) and synthesis of chlorophyll. [ 17 ]  In others, it substitutes for  potassium  in several roles, such as maintaining  turgor pressure  and aiding in the opening and closing of stomata. [ 18 ]  Excess sodium in the soil limits the uptake of water due to decreased  water potential , which may result in wilting; similar concentrations in the  cytoplasm  can lead to enzyme inhibition, which in turn causes necrosis and chlorosis. [ 19 ]  To avoid these problems, plants developed mechanisms that limit sodium uptake by roots, store them in cell  vacuoles , and control them over long distances; [ 20 ]  excess sodium may also be stored in old plant tissue, limiting the damage to new growth. Though much how excess sodium loading in the xylem is yet to be determined. However, anti porter CHX21 can be attributed to active loading of sodium into the xylem. [ 21 ]


Sodium is the primary  cation  (positively charged ion) in extracellular fluids in animals and humans. These fluids, such as blood plasma and extracellular fluids in other tissues, bathe cells and carry out transport functions for nutrients and wastes. Sodium is also the principal cation in seawater, although the concentration there is about 3.8 times what it is normally in extracellular body fluids.


Although the system for maintaining optimal salt and water balance in the body is a complex one, [ 22 ]  one of the primary ways in which the human body keeps track of loss of body water is that  osmoreceptors  in the  hypothalamus  sense a balance of sodium and water concentration in extracellular fluids. Relative loss of body water will cause sodium concentration to rise higher than normal, a condition known as  hypernatremia . This ordinarily results in thirst. Conversely, an excess of body water caused by drinking will result in too little sodium in the blood ( hyponatremia ), a condition which is again sensed by the  hypothalamus , causing a decrease in  vasopressin  hormone secretion from the  posterior pituitary , and a consequent loss of water in the urine, which acts to restore blood sodium concentrations to normal.


Severely dehydrated persons, such as people rescued from ocean or desert survival situations, usually have very high blood sodium concentrations. These must be very carefully and slowly returned to normal, since too-rapid correction of hypernatremia may result in brain damage from cellular swelling, as water moves suddenly into cells with high  osmolar  content.


In humans, a high-salt intake was demonstrated to attenuate  nitric oxide  production. Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. [ 23 ]


Because the  hypothalamus / osmoreceptor  system ordinarily works well to cause drinking or urination to restore the body's sodium concentrations to normal, this system can be used in medical treatment to regulate the body's total fluid content, by first controlling the body's sodium content. Thus, when a powerful  diuretic  drug is given which causes the kidneys to excrete sodium, the effect is accompanied by an excretion of body water (water loss accompanies sodium loss). This happens because the kidney is unable to efficiently retain water while excreting large amounts of sodium. In addition, after sodium excretion, the  osmoreceptor  system may sense lowered sodium concentration in the blood and then direct compensatory urinary water loss in order to correct the  hyponatremic  (low blood sodium) state.


The  sodium-potassium pump  works with the sodium and potassium leak channels to maintain the membrane potential between the cell and the extracellular space. Sodium moves down the concentration gradient from the cytosol into the extracellular matrix. Potassium moves down its concentration gradient from the extracellular matrix into the cytosol. In order to maintain the membrane potential, the sodium-potassium pump acts as a form of direct active transport where the hydrolysis of ATP to ADP and an inorganic phosphate at the P-type ATPase moves 3 potassium ions back out of the cell and 2 sodium ions into the cell. [ 4 ]


The sodium-potassium pump plays a large role in neural signaling due to the maintenance of cell membrane potential. This creates an action potential that causes the neurons to polarize and depolarize their membranes by opening and closing the voltage gated channels: this alters voltage potential and leads to neurotransmitter secretion and ultimately signal transmission. [ 24 ]


When the pump fails to function, patients are susceptible to illnesses like heart failure and chronic obstructive lung disease (COLD). Those who experienced an event of heart failure had on average, a 40% lower concentration of the sodium-potassium ATPase. This lack of polarization of the membrane leads to an inability of action potentials to propagate at their usual rate, leading to a lowered hear rate and potentially heart failure. [ 25 ]  In COLD diagnoses, a majority of patients found to have a lowered amount of magnesium and potassium also had a decreased concentration of the sodium-potassium pump in skeletal and smooth muscle during respiratory failure. COLD is treatable in the short term by glucocorticoid which up-regulates the sodium-potassium pump, helping to support muscle endurance and increase muscle activity during these episodes of respiratory failure. [ 26 ]


In the  sodium-glucose symporter , sodium moves down its concentration gradient to move glucose up its concentration gradient. Sodium has a greater concentration outside of the cell, and binds to the symporter, which is in its outward facing conformation. Once sodium is bound, glucose can bind from the extracellular space, causing the symporter to switch into the occluded formation (closed) before opening to the inside of the cell and releasing the two sodium ions and the one glucose molecule. Once both are released, the symporter re-orients itself to the outward facing conformation and the process starts all over again. [ 4 ]  A major example of up-regulation of the sodium-glucose symporter is seen in patients with  type 2 diabetes , where there is roughly a 3-4 fold up-regulation of the sodium-glucose symporter (SGLT1). This leads to an influx of glucose into the cell and results in hyperglycemia. [ 27 ]


The  Cystic Fibrosis Transport Regulator (CFTR)  works by binding two ATP to the A1 and A2, ATP-binding domain. This opens the CFTR channel and allows chloride ions to flow into the lungs and airway lumen. This influx of negatively charged chloride ions into the airway lumen causes sodium to move into the airway lumen to balance the negative charge. Water then moves in with the sodium to balance the osmotic pressure and ultimately leads to the thinning of mucus. In cases of Cystic Fibrosis, the CFTR is defective and only binds a single ATP, leading to the channel failing to open and preventing chloride ions from diffusing into the airway lumen. Since chloride ions cannot diffuse in, there is no movement of sodium into the airway lumen, and no need for water to move into the lumen, leading to thick mucus that clogs and infects the airway lumen. [ 4 ]


Sulfur assimilation  is the process by which living organisms incorporate  sulfur  into their biological molecules. [ 1 ]  In plants, sulfate is absorbed by the roots and then transported to the chloroplasts by the transipration stream where the sulfur are reduced to  sulfide  with the help of a series of  enzymatic reactions . Furthermore, the reduced sulfur is incorporated into  cysteine , [ 2 ]  an amino acid that is a precursor to many other sulfur-containing compounds. In animals, sulfur assimilation occurs primarily through the diet, as animals cannot produce sulfur-containing compounds directly. Sulfur is incorporated into amino acids such as  cysteine  and  methionine , which are used to build  proteins  and other important molecules. [ 2 ]


Sulfate  uptake first occurs in roots that have a high affinity for sulfur.  [ 3 ]  The maximal sulfate uptake rate is generally already reached at sulfate levels of 0.1 mM and lower. The uptake of sulfate by the roots and its transport to the shoot is strictly controlled and it appears to be one of the primary regulatory sites of sulfur assimilation. [ 3 ]


Sulfate is actively taken up across the  plasma membrane  of the  root  cells, subsequently loaded into the  xylem  vessels and transported to the shoot by the  transpiration  stream.  [ 4 ]  The uptake and transport of sulfate is energy dependent (driven by a  proton gradient  generated by  ATPases ) through a proton/sulfate  co-transport . [ 5 ]  In the shoot the sulfate is unloaded and transported to the chloroplasts where it is reduced. The remaining sulfate in plant tissue is predominantly present in the  vacuole , since the concentration of sulfate in the  cytoplasm  is kept rather constant.


Distinct sulfate transporter proteins mediate the uptake, transport and subcellular distribution of sulfate. [ 6 ]  The sulfate  transporters   gene family  has been classified in up to 5 different groups according to their cellular and sub-cellular  gene expression , and possible functioning. [ 7 ]  Each group of transporter proteins may be expressed exclusively in the roots or shoots of the plant, or both.


Regulation and expression of the majority of sulfate transporters are controlled by the sulfur  nutritional  status of the plants. [ 8 ]  Upon sulfate deprivation, the rapid decrease in root sulfate is regularly accompanied by a strongly enhanced expression of most sulfate transporter genes (up to 100-fold), accompanied by a substantially enhanced sulfate uptake capacity. It is not yet fully understood whether sulfate and other metabolic products of sulfur assimilation ( O-acetylserine ,  cysteine ,  glutathione ) act as signals in the regulation of sulfate uptake and transport, or in the expression of the sulfate transporters involved.


Sulfate reduction predominantly takes place in the leaf  chloroplasts . Here, the reduction of  sulfate  to  sulfide  occurs in three steps. Sulfate needs to be activated to  adenosine 5'-phosphosulfate  (APS) prior to its reduction to  sulfite .


The activation of sulfate is catalyzed by  ATP  sulfurylase, which affinity for sulfate is rather low (Km approximately 1 mM) and the in situ sulfate concentration in the chloroplast is most likely one of the limiting/regulatory steps in sulfur reduction. Subsequently, APS is reduced to sulfite, catalyzed by APS reductase with likely  glutathione  as  reductant .


The latter reaction is assumed to be one of the primary regulation points in the sulfate reduction, since the activity of APS reductase is the lowest of the enzymes of the sulfate reduction pathway and it has a fast turnover rate.  Sulfite  is with high affinity reduced by  sulfite reductase  to  sulfide  with  ferredoxin  as a reductant. The remaining sulfate in plant tissue is transferred into the  vacuole . The remobilization and redistribution of the vacuolar sulfate reserves appear to be rather slow and sulfur-deficient plants may still contain detectable levels of sulfate.


Sulfide  is incorporated into  cysteine , catalyzed by O-acetylserine (thiol)lyase, with O-acetylserine as substrate. The synthesis of O-acetylserine is catalyzed by  serine  acetyltransferase and together with O-acetylserine (thiol)lyase it is associated as enzyme complex named  cysteine synthase .


The formation of cysteine is the direct coupling step between sulfur ( sulfur metabolism ) and  nitrogen assimilation  in plants. This differs from the process in yeast, where sulfide must be incorporated first in  homocysteine  then converted in two steps to cysteine.


Cysteine is sulfur donor for the synthesis of  methionine , the major other sulfur-containing amino acid present in plants. This happens through the  transsulfuration pathway  and the methylation of  homocysteine .


Both cysteine and methionine are sulfur-containing  amino acids  and are of great significance in the structure, conformation and function of  proteins  and  enzymes , but high levels of these amino acids may also be present in seed storage proteins. The thiol groups of the cysteine residues in proteins can be oxidized resulting in  disulfide  bridges with other cysteine  side chains  (and form  cystine ) and/or linkage of  polypeptides .


Disulfide bridges ( disulfide bonds ) make an important contribution to the structure of proteins. The  thiol  groups are also of great importance in substrate binding of enzymes, in metal-sulfur clusters in proteins (e.g.  ferredoxins ) and in regulatory proteins (e.g.  thioredoxins ).


Glutathione  or its homologues, e.g. homoglutathione in  Fabaceae ; hydroxymethylglutathione in  Poaceae  are the major water-soluble non- protein   thiol  compounds present in plant tissue and account for 1-2% of the total sulfur. The content of glutathione in plant tissue ranges from 0.1 – 3 mM. Cysteine is the direct precursor for the synthesis of glutathione (and its homologues). First, γ-glutamylcysteine is synthesized from cysteine and glutamate catalyzed by  gamma-glutamylcysteine synthetase . Second, glutathione is synthesized from γ-glutamylcysteine and  glycine  (in glutathione homologues,  β-alanine  or  serine ) catalyzed by glutathione synthetase. Both steps of the synthesis of glutathione are ATP dependent reactions. Glutathione is maintained in the reduced form by an  NADPH -dependent  glutathione reductase  and the ratio of reduced glutathione (GSH) to  oxidized  glutathione (GSSG) generally exceeds a value of 7.
Glutathione fulfils various roles in plant functioning. In sulfur metabolism it functions as reductant in the reduction of APS to sulfite. It is also the major transport form of reduced sulfur in plants. Roots likely largely depend for their reduced sulfur supply on shoot/root transfer of glutathione via the  phloem , since the reduction of sulfur occurs predominantly in the chloroplast. Glutathione is directly involved in the reduction and assimilation of  selenite  into  selenocysteine . Furthermore, glutathione is of great significance in the protection of plants against oxidative and environmental stress and it depresses/scavenges the formation of toxic  reactive oxygen species , e.g.  superoxide ,  hydrogen peroxide  and lipid  hydroperoxides . Glutathione functions as reductant in the enzymatic detoxification of reactive oxygen species in the glutathione- ascorbate  cycle and as thiol buffer in the protection of proteins via direct reaction with reactive oxygen species or by the formation of mixed disulfides. The potential of glutathione as protectant is related to the pool size of glutathione, its redox state (GSH/GSSG ratio) and the activity of  glutathione reductase . Glutathione is the precursor for the synthesis of phytochelatins, which are synthesized enzymatically by a constitutive phytochelatin synthase. The number of γ-glutamyl-cysteine residues in the phytochelatins may range from 2 – 5, sometimes up to 11. Despite the fact that the  phytochelatins  form complexes which a few heavy metals, viz.  cadmium , it is assumed that these compounds play a role in heavy metal  homeostasis  and detoxification by buffering of the cytoplasmatic concentration of essential heavy metals. Glutathione is also involved in the detoxification of  xenobiotics , compounds without direct nutritional value or significance in metabolism, which at too high levels may negatively affect plant functioning. Xenobiotics may be detoxified in conjugation reactions with glutathione catalyzed by  glutathione S-transferase , which activity is constitutive; different xenobiotics may induce distinct  isoforms  of the enzyme. Glutathione S-transferases have great significance in  herbicide  detoxification and tolerance in agriculture and their induction by herbicide  antidotes  (' safeners ') is the decisive step for the induction of herbicide tolerance in many crop plants. Under natural conditions glutathione S-transferases are assumed to have significance in the detoxification of lipid  hydroperoxides , in the conjugation of endogenous metabolites,  hormones  and  DNA  degradation products, and in the transport of  flavonoids .


Sulfolipids  are sulfur containing lipids.  Sulfoquinovosyl diacylglycerols  are the predominant sulfolipids present in plants. In leaves its content comprises up to 3 - 6% of the total sulfur present. This sulfolipid is present in  plastid   membranes  and likely is involved in  chloroplast  functioning. The route of  biosynthesis  and physiological function of sulfoquinovosyl  diacylglycerol  is still under investigation. From recent studies it is evident that  sulfite  it the likely sulfur  precursor  for the formation of the  sulfoquinovose  group of this lipid.


Brassica  species contain  glucosinolates , which are sulfur-containing  secondary compounds . Glucosinolates are composed of a β-thioglucose moiety, a sulfonated oxime and a side chain. The synthesis of glucosinolates starts with the oxidation of the parent amino acid to an  aldoxime , followed by the addition of a thiol group (through conjugation with glutathione) to produce  thiohydroximate . The transfer of a  glucose  and a sulfate moiety completes the formation of the glucosinolates.


The physiological significance of glucosinolates is still ambiguous, though they are considered to function as sink compounds in situations of sulfur excess. Upon tissue disruption glucosinolates are enzymatically degraded by  myrosinase  and may yield a variety of biologically active products such as  isothiocyanates ,  thiocyanates ,  nitriles  and oxazolidine-2-thiones. The glucosinolate-myrosinase system is assumed to play a role in plant- herbivore  and plant- pathogen  interactions.


Furthermore, glucosinolates are responsible for the flavor properties of  Brassicaceae  and recently
have received attention in view of their potential anti- carcinogenic  properties.
 Allium  species contain γ- glutamylpeptides  and  alliins  (S-alk(en)yl cysteine sulfoxides). The content of these sulfur-containing  secondary compounds  strongly depends on stage of development of the plant, temperature, water availability and the level of nitrogen and sulfur nutrition. In onion  bulbs  their content may account for up to 80% of the organic sulfur fraction. Less is known about the content of secondary sulfur compounds in the seedling stage of the plant.


It is assumed that alliins are predominantly synthesized in the leaves, from where they are subsequently transferred to the attached bulb scale. The biosynthetic pathways of synthesis of γ-glutamylpeptides and alliins are still ambiguous. γ-Glutamylpeptides can be formed from cysteine (via γ-glutamylcysteine or glutathione) and can be metabolized into the corresponding alliins via oxidation and subsequent hydrolyzation by γ-glutamyl  transpeptidases .


However, other possible routes of the synthesis of γ-glutamylpeptides and alliins may not be excluded. Alliins and γ-glutamylpeptides are known to have therapeutic utility and might have potential value as phytopharmaceutics. The alliins and their breakdown products (e.g.  allicin ) are the flavor precursors for the odor and taste of species. Flavor is only released when plant cells are disrupted and the enzyme alliinase from the vacuole is able to degrade the alliins, yielding a wide variety of volatile and non- volatile  sulfur-containing compounds. The physiological function of γ-glutamylpeptides and alliins is rather unclear.


Unlike in plants, animals do not have a pathway for the direct assimilation of inorganic sulfate into organic compounds. In animals, the primary source of sulfur is dietary  methionine , an essential amino acid that contains a sulfur atom. Methionine is first converted to  S-adenosylmethionine  (SAM), a compound that is involved in many important biological processes, including DNA  methylation  and  neurotransmitter  synthesis.


SAM can then be used to synthesize other important sulfur-containing compounds such as  cysteine ,  taurine , and  glutathione . Cysteine is a precursor for the synthesis of several important proteins and peptides, as well as glutathione, a powerful antioxidant that protects cells from oxidative stress.  Taurine  is involved in a variety of physiological processes, including  osmoregulation ,  modulation  of  calcium signaling , and regulation of mitochondrial function.


In  bacteria  and  fungi , the sulfur assimilation pathway is similar to that in plants, where inorganic sulfate is reduced to sulfide, and then incorporated into cysteine and other sulfur-containing compounds.


Bacteria and fungi can absorb inorganic sulfate from the environment through a sulfate transporter, which is regulated by the presence of sulfate in the medium. Once inside the cell, sulfate is activated by  ATP sulfurylase  to form  adenosine 5'-phosphosulfate  (APS), which is then reduced to sulfite by APS reductase. Sulfite is further reduced to sulfide by sulfite reductase, which is then incorporated into cysteine by enzyme.


Cysteine, once synthesized, can be used for the biosynthesis of  methionine  and other important biomolecules. In addition, microorganisms also use sulfur-containing compounds for various other purposes, such as the synthesis of  antibiotics .


Sulfur assimilation in microorganisms is regulated by a variety of environmental factors, including the availability of sulfur in the medium and the presence of other nutrients. The activity of key enzymes in the sulfur assimilation pathway is also regulated by feedback inhibition from downstream products, similar to the regulation seen in plants.


The rapid economic growth, industrialization and urbanization are associated with a strong increase in energy demand and emissions of  air pollutants  including  sulfur dioxide  (see also  acid rain ) and  hydrogen sulfide , which may affect plant  metabolism . Sulfur gases are potentially  phytotoxic , however, they may also be metabolized and used as sulfur source and even be beneficial if the sulfur  fertilization  of the roots is not sufficient.


Plant shoots form a sink for atmospheric  sulfur  gases, which can directly be taken up by the foliage (dry deposition). The foliar uptake of sulfur dioxide is generally directly dependent on the degree of opening of the  stomates , since the internal resistance to this gas is low. Sulfite is highly soluble in the  apoplastic  water of the  mesophyll , where it  dissociates  under formation of  bisulfite  and  sulfite .


Sulfite may directly enter the sulfur reduction pathway and be reduced to  sulfide , incorporated into cysteine, and subsequently into other sulfur compounds. Sulfite may also be oxidized to  sulfate , extra- and intracellularly by  peroxidases  or non-enzymatically catalyzed by metal ions or  superoxide   radicals  and subsequently reduced and assimilated again. Excessive sulfate is transferred into the vacuole; enhanced foliar sulfate levels are characteristic for exposed plants.
The foliar uptake of hydrogen sulfide appears to be directly dependent on the rate of its metabolism into cysteine and subsequently into other sulfur compounds. There is strong evidence that O-acetyl-serine (thiol)lyase is directly responsible for the active fixation of atmospheric hydrogen sulfide by plants.


Plants are able to transfer from sulfate to foliar absorbed atmospheric sulfur as sulfur source and levels of 60  ppb  or higher appear to be sufficient to cover the sulfur requirement of plants. There is an interaction between atmospheric and pedospheric sulfur utilization. For instance, hydrogen sulfide exposure may result in a decreased activity of APS reductase and a depressed sulfate uptake.


Zinc  is an essential  trace element  for humans [ 1 ] [ 2 ] [ 3 ]  and other animals, [ 4 ]  for plants [ 5 ]  and for  microorganisms . [ 6 ]  Zinc is required for the function of over 300  enzymes  and 1000  transcription factors , [ 3 ]  and is stored and transferred in  metallothioneins . [ 7 ] [ 8 ]  It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all  enzyme classes . [ 5 ] [ 3 ]


In proteins, zinc ions are often coordinated to the amino acid side chains of  aspartic acid ,  glutamic acid ,  cysteine  and  histidine . The theoretical and computational description of this zinc binding in proteins (as well as that of other  transition metals ) is difficult. [ 9 ]


Roughly  2–4  grams of zinc [ 10 ]  are distributed throughout the human body. Most zinc is in the brain, muscle, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye. [ 11 ]   Semen  is particularly rich in zinc, a key factor in  prostate gland  function and  reproductive organ  growth. [ 12 ]


Zinc homeostasis of the body is mainly controlled by the intestine. Here,  ZIP4  and especially  TRPM7  were linked to intestinal zinc uptake essential for postnatal survival. [ 13 ] [ 14 ]


In humans, the biological roles of zinc are ubiquitous. [ 15 ] [ 2 ]  It interacts with "a wide range of organic  ligands ", [ 15 ]  and has roles in the metabolism of RNA and DNA,  signal transduction , and  gene expression . It also regulates  apoptosis . A review from 2015 indicated that about 10% of human proteins (~3000) bind zinc, [ 16 ]  in addition to hundreds more that transport and traffic zinc; a similar  in silico  study in the plant  Arabidopsis thaliana  found 2367 zinc-related proteins. [ 5 ]


In the  brain , zinc is stored in specific  synaptic vesicles  by  glutamatergic   neurons  and can modulate neuronal excitability. [ 2 ] [ 3 ] [ 17 ]  It plays a key role in  synaptic plasticity  and so in learning. [ 2 ] [ 18 ]  Zinc  homeostasis  also plays a critical role in the functional regulation of the  central nervous system . [ 2 ] [ 17 ] [ 3 ]  Dysregulation of zinc homeostasis in the central nervous system that results in excessive synaptic zinc concentrations is believed to induce  neurotoxicity  through mitochondrial oxidative stress (e.g., by disrupting certain enzymes involved in the  electron transport chain , including  complex I ,  complex III , and  α-ketoglutarate dehydrogenase ), the dysregulation of calcium homeostasis, glutamatergic neuronal  excitotoxicity , and interference with intraneuronal  signal transduction . [ 2 ] [ 19 ]  L- and D-histidine facilitate brain zinc uptake. [ 20 ]   SLC30A3  is the primary  zinc transporter  involved in cerebral zinc homeostasis. [ 2 ]


Zinc is an efficient  Lewis acid , making it a useful catalytic agent in  hydroxylation  and other enzymatic reactions. [ 21 ]  The metal also has a flexible  coordination geometry , which allows proteins using it to rapidly shift  conformations  to perform biological reactions. [ 22 ]  Two examples of zinc-containing enzymes are  carbonic anhydrase  and  carboxypeptidase , which are vital to the processes of  carbon dioxide  ( CO 2 ) regulation and digestion of proteins, respectively. [ 23 ]


In vertebrate blood, carbonic anhydrase converts  CO 2  into bicarbonate and the same enzyme transforms the bicarbonate back into  CO 2  for exhalation through the lungs. [ 24 ]  Without this enzyme, this conversion would occur about one million times slower [ 25 ]  at the normal blood  pH  of 7 or would require a pH of 10 or more. [ 26 ]  The non-related β-carbonic anhydrase is required in plants for leaf formation, the synthesis of  indole acetic acid  (auxin) and  alcoholic fermentation . [ 27 ]


Carboxypeptidase cleaves peptide linkages during digestion of proteins. A  coordinate covalent bond  is formed between the terminal peptide and a C=O group attached to zinc, which gives the carbon a positive charge. This helps to create a  hydrophobic  pocket on the enzyme near the zinc, which attracts the non-polar part of the protein being digested. [ 23 ]


Zinc has been recognized as a messenger, able to activate signalling pathways. Many of these pathways provide the driving force in aberrant cancer growth. They can be targeted through  ZIP transporters . [ 28 ]


Zinc serves a purely structural role in  zinc fingers , twists and clusters. [ 29 ]  Zinc fingers form parts of some  transcription factors , which are proteins that recognize  DNA base sequences  during the replication and transcription of  DNA . Each of the nine or ten  Zn 2+  ions in a zinc finger helps maintain the finger's structure by coordinately binding to four  amino acids  in the transcription factor. [ 25 ]


In  blood plasma , zinc is bound to and transported by  albumin  (60%, low-affinity) and  transferrin  (10%). [ 10 ]  Because transferrin also transports iron, excessive iron reduces zinc absorption, and vice versa. A similar antagonism exists with copper. [ 30 ]  The concentration of zinc in blood plasma stays relatively constant regardless of zinc intake. [ 21 ]  Cells in the salivary gland, prostate, immune system, and intestine use  zinc signaling  to communicate with other cells. [ 31 ]


Zinc may be held in  metallothionein  reserves within microorganisms or in the intestines or liver of animals. [ 32 ]  Metallothionein in intestinal cells is capable of adjusting absorption of zinc by 15–40%. [ 33 ]  However, inadequate or excessive zinc intake can be harmful; excess zinc particularly impairs copper absorption because metallothionein absorbs both metals. [ 34 ]


The human  dopamine transporter  contains a  high affinity  extracellular zinc  binding site  which, upon zinc binding, inhibits dopamine  reuptake  and amplifies  amphetamine -induced  dopamine efflux   in vitro . [ 35 ] [ 36 ] [ 37 ]  The human  serotonin transporter  and  norepinephrine transporter  do not contain zinc binding sites. [ 37 ]  Some  EF-hand   calcium binding proteins  such as  S100  or  NCS-1  are also able to bind zinc ions. [ 38 ]


The  U.S. Institute of Medicine  (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for zinc in 2001. The current EARs for zinc for women and men ages 14 and up is 6.8 and 9.4 mg/day, respectively. The RDAs are 8 and 11 mg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher-than-average requirements. RDA for pregnancy is 11 mg/day. RDA for lactation is 12 mg/day. For infants up to 12 months, the RDA is 3 mg/day. For children ages 1–13 years, the RDA increases with age from 3 to 8 mg/day. As for safety, the IOM sets  Tolerable upper intake levels  (ULs) for vitamins and minerals when evidence is sufficient. In the case of zinc the adult UL is 40 mg/day (lower for children). Collectively the EARs, RDAs, AIs and ULs are referred to as  Dietary Reference Intakes  (DRIs). [ 21 ]


The  European Food Safety Authority  (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the United States. For people ages 18 and older, the PRI calculations are complex, as the EFSA has set higher and higher values as the  phytate  content of the diet increases. For women, PRIs increase from 7.5 to 12.7 mg/day as phytate intake increases from 300 to 1200 mg/day; for men, the range is 9.4 to 16.3 mg/day. These PRIs are higher than the U.S. RDAs. [ 39 ]  The EFSA reviewed the same safety question and set its UL at 25 mg/day, which is much lower than the U.S. value. [ 40 ]


For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For zinc labeling purposes, 100% of the Daily Value was 15 mg, but on May 27, 2016, it was revised to 11 mg. [ 41 ] [ 42 ]  A table of the old and new adult daily values is provided at  Reference Daily Intake .