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High resolution three-dimensional models of molecules in cells will help explain the intricate biochemical interactions among proteins.
#### **KEY TERMS**
actin filaments 174
apical 153
basolateral 153
chloroplast 172
cytoskeleton 147
cytosol 147
cytosolic face 150
endoplasmic
reticulum (ER) 168
endosome 165
exop... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
2001. Potassium channels: life in the post-structural world. *Curr. Opin. Struc. Biol.* **11**:408–414.
Schulz, G. E. 2000. -Barrel membrane proteins. *Curr. Opin. Struc. Biol.* **10**:443–447.
#### Organelles of the Eukaryotic Cell
Bainton, D. 1981. The discovery of lysosomes. *J. Cell Biol.* **91**:66s–76s.
C... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
Model of inflammatory bowel disease in which cultured flat colonic smooth muscle cells were induced to secrete cables of hyaluronan (green) that bind to spheroidal mononuclear leukocytes via their CD44 receptors (red). Nuclei are stained blue. [Courtesy of C. de la Motte et al., Lerner R... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
Heterodimeric integrins (for example, v and -3 chains) function as CAMs or as adhesion
receptors (shown here) that bind to very large, multiadhesive matrix proteins such as fibronectin, only a small part of which is shown here (see also Figure 6-25). Note that CAMs often form higher-order oligomers within the plane o... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
These interactions bind cells into tissues and facilitate communication between cells and their environments.
- The cytosolic domains of CAMs and adhesion receptors bind multifunctional adapter proteins that mediate interaction with cytoskeletal fibers and intracellular signaling proteins.
- The major families of cell-... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
The primary CAMs in adherens junctions and desmosomes belong to the **cadherin** family. In vertebrates and invertebrates, this protein family of more than 100 members can be grouped into at least six subfamilies. The diversity of cadherins arises from the presence of multiple cadherin genes and alternative RNA splicin... | {
"Header 1": "▲ FIGURE 4-13 Structure of the 5' methylated cap of eukaryotic mRNA. The distinguishing chemical features are the 5'→5' linkage of 7-methylguanylate to the initial nucleotide of the mRNA molecule and the methyl group on the 2' hydroxyl of the ribose of the first nucleotide (base 1). Both these features... |
the cytoskeleton and participate in intracellular signaling pathways (e.g., $\beta$ -catenin). Somewhat different sets of adapter proteins are illustrated in the two cells shown to emphasize that a variety of adapters can interact with adherens junctions, which can thereby participate in diverse activities. [Adapted f... | {
"Header 1": "▲ FIGURE 6-7 Protein constitutents of typical adherens junctions. The exoplasmic domains of E-cadherin dimers clustered at adherens junctions on adjacent cells (1 and 2) form Ca<sup>+2</sup>-dependent homophilic interactions. The cytosolic domains of the E-cadherins bind directly or indirectly to multi... |
Cell Biol.* **2**:285.]
Tight junctions prevent the diffusion of macromolecules and to varying degrees impede the diffusion of small watersoluble molecules and ions across an epithelial sheet in the spaces between cells. T... | {
"Header 1": "▲ FIGURE 6-7 Protein constitutents of typical adherens junctions. The exoplasmic domains of E-cadherin dimers clustered at adherens junctions on adjacent cells (1 and 2) form Ca<sup>+2</sup>-dependent homophilic interactions. The cytosolic domains of the E-cadherins bind directly or indirectly to multi... |
studied by measuring ion flux (electrical resistance) or the movement of radioactive or fluorescent molecules across monolayers of MDCK cells.
The importance of paracellular transport is illustrated in several human diseases. In hereditary hypomagnesemia, defects in the *claudin16* ge... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
The **integrin** family comprises heterodimeric integral membrane proteins that function as adhesion receptors, mediating many cell–matrix interactions (see Figure 6-2). In vertebrates, at least 24 integrin heterodimers, composed of 18 types of $\alpha$ subunits and 8 types of $\beta$ subunits in various combinatio... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Four ubiquitous protein components are found in basal laminae (Figure 6-13):
- *Type IV collagen,* trimeric molecules with both rodlike and globular domains that form a two-dimensional network
- *Laminins,* a family of multiadhesive proteins that form a fibrous two-dimensional network with type IV collagen and that a... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
(a) Schematic model showing the general shape, location of globular domains, and coiled-coil region in which laminin's three chains are covalently linked by several disulfide bonds. Different regions of laminin bind to cell-surface receptors and various matrix components. (b) Electron micrographs of intact laminin mole... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Like that of many integral membrane proteins, the cytosolic domain of syndecan interacts with the actin cytoskeleton and in some cases with intracellular regulatory molecules. In addition, cell-surface proteoglycans bind many protein growth factors and other external signaling molecules, thereby helping to regulate cel... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
We have seen how diverse CAMs and adhesion receptors participate in the assembly of animal cells into epithelial sheets that rest on and adhere to a well-defined ECM structure, the basal lamina. The same or similar molecules mediate and control cell-cell and cell-matrix interactions in
connective, muscle, and neural ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Connective tissue, such as tendon and cartilage, differs from other solid tissues in that most of its volume is made up of extracellular matrix rather than cells. This matrix is packed with insoluble protein fibers and contains proteoglycans, various multiadhesive proteins, and **hyaluronan**, a very large, nonsulfated... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Collagen biosynthesis and secretion follow the normal pathway for a secreted protein, which is described in detail in Chapters 16 and 17. The collagen $\alpha$ chains are synthesized as longer precursors, called pro- $\alpha$ chains, by ribosomes attached to the endoplasmic reticulum (ER). The pro- $\alpha$ chains ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Certain mutations in the genes encoding collagen 1(I) or 2(I) chains, which form type I collagen, lead to *osteogenesis imperfecta,* or brittle-bone dis-
ease. Because every third position in a collagen chain must be a glycine for the triple helix to form (see Figure 6-14), mutations of glycine to almost any other ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Conversely, by regulating their receptor-mediated attachments to fibronectin and other ECM components, cells can sculpt the immediate ECM environment to suit their needs.
Fibronectins are dimers of two similar polypeptides linked at their C-termini by two disulfide bonds; each chain is about 60–70 nm long and 2–3 nm ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
The force needed to unfold and expose functional selfassociation sites in fibronectin is much less than that needed to disrupt fibronectin–integrin binding. Thus fibronectin molecules remain bound to integrin while cellgenerated mechanical forces induce fibril formation. In effect, the integrins through adapter prote... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
All integrins appear to have evolved from two ancient general subgroups: those that bind RGD-containing molecules (e.g., fibronectin) and those that bind laminin. For example, $\alpha 5\beta 1$ integrin binds fibronectin, whereas the widely expressed $\alpha 1\beta 1$ and $\alpha 2\beta 1$ integrins, as well as... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Cells can exquisitely control the strength of integrinmediated cell-matrix interactions by regulating the ligandbinding activity of integrins or their expression or both. Such regulation is critical to the role of these interactions in cell migration and other functions.
Many, if not all, integrins can exist in two c... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Mutations in dystrophin, other DGC components, laminin, or enzymes that add the *O*-linked sugars to dystroglycan disrupt the DGC-mediated link between the exterior and the interior of muscle cells and cause muscular dystrophies. In addition, dystroglycan mutations have been shown to greatly reduce the clustering of ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Different types of leukocytes express specific integrins containing the -2 subunit: for example, L-2 by T lymphocytes and M-2 by monocytes, the circulating precursors of tissue macrophages. Nonetheless, all leukocytes move into tissues by the same general mechanism depicted in Figure 6-30.
Many of the CAMs used to di... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Most cells, however, express at least two connexins; these different proteins assemble into hetero-oligomeric connexons, which in turn form heterotypic gap-junction channels. This diversity in channel composition leads to differences in the permeability of channels to various molecules. For example, channels made from ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
The amount, type, and direction of plant cell growth are regulated by small-molecule hormones (e.g., indoleacetic acid) called *auxins.* The auxin-induced weakening of the cell wall permits the expansion of the intracellular vacuole by uptake of water, leading to elongation of the cell. We can grasp the magnitude of th... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Plant cells can communicate directly through specialized cell–cell junctions called **plasmodesmata**, which extend through the cell wall. Like gap junctions, plasmodesmata are open channels that connect the cytosol of a cell with that of an adjacent cell. The diameter of the cytosol-filled channel is about 30–60 nm, a... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
In addition, as already described, the three-dimensional distribution of cells and extracellular matrix around a cell influences its shape and behavior. Because the immediate environment of cultured cells differs radically from this "normal" environment, their properties may be affected in various ways. Thus care must ... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
Normal animal tissues (e.g., skin, kidney, liver) or whole embryos are commonly used to establish *primary cell cultures*. To prepare tissue cells for a primary culture, the cell–cell and cell–matrix interactions must be broken. To do so, tissue fragments are treated with a combination of a protease (e.g., trypsin or t... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
To be able to clone individual cells, modify cell behavior, or select mutants, biologists often want to maintain cell cultures for many more than 100 doublings. Such prolonged growth is exhibited by cells derived from some tumors. In addition, rare cells in a population of primary cells that undergo certain spontaneous... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
In this case, normal B lymphocytes are fused with myeloma cells that cannot grow in *HAT medium,* the most common selection medium used in the production of hybridomas*.* Only the myelomalymphocyte hybrids can survive and grow for an extended period in HAT medium for reasons described shortly. Thus, this selection medi... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
The principles underlying HAT selection are important not only for understanding how hybridoma cells are isolated but also for understanding several other frequently used selection methods, including selection of the ES cells used in generating knockout mice (Chapter 9). HAT medium contains hypoxanthine (a purine), ami... | {
"Header 1": "▲ FIGURE 6-11 Transcellular and paracellular pathways of transepithelial transport. Transcellular transport requires the cellular uptake of molecules on one side and subsequent release on the opposite side by mechanisms discussed in Chapters 7 and 17. In paracellular transport, molecules move extracell... |
tetrahydrofolate, preventing purine and thymidylate synthesis. Many animal cells can also use salvage pathways (red) to incorporate purine bases or nucleosides and thymidine. If these precursors are present in the medium, normal cells will grow even in the presence of antifolates. Cultured cells lacking one of the enzy... | {
"Header 1": "▲ FIGURE 6-39 De novo and salvage pathways for nucleotide synthesis. Animal cells can synthesize purine nucleotides (AMP, GMP, IMP) and thymidylate (TMP) from simpler compounds by de novo pathways (blue). They require the transfer of a methyl or formyl (\"CHO\") group from an activated form of tetrahyd... |
Explain why the process of cell fusion is necessary to produce monoclonal antibodies used for research.
#### **ANALYZE THE DATA**
Researchers have isolated two E-cadherin mutant isoforms that are hypothesized to function differently from that of the wild-type E-cadherin. An E-cadherin negative mammary carcinoma cel... | {
"Header 1": "▲ FIGURE 6-39 De novo and salvage pathways for nucleotide synthesis. Animal cells can synthesize purine nucleotides (AMP, GMP, IMP) and thymidylate (TMP) from simpler compounds by de novo pathways (blue). They require the transfer of a methyl or formyl (\"CHO\") group from an activated form of tetrahyd... |
2002. Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. *Curr. Opin. Genet. Devel.* **12**:349–361.
Geiger, B., A. Bershadsky, R. Pankov, and K. M. Yamada. 2001. Transmembrane crosstalk between the extracellular matrix and the cytoskeleton. *Nature Rev. Mol. Cell... | {
"Header 1": "▲ FIGURE 6-39 De novo and salvage pathways for nucleotide synthesis. Animal cells can synthesize purine nucleotides (AMP, GMP, IMP) and thymidylate (TMP) from simpler compounds by de novo pathways (blue). They require the transfer of a methyl or formyl (\"CHO\") group from an activated form of tetrahyd... |
Aquaporin, the water channel, consists of four identical transmembrane polypeptides.
he plasma membrane is a selectively permeable barrier between the cell and the extracellular environment. Its permeability properties ensure that essential molecules such as ions, glucose, amino acids,... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"token_count": 731,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Gases, such as O<sub>2</sub> and CO<sub>2</sub>, and small, uncharged polar molecules, such as urea and ethanol, can readily move by **passive** (**simple**) **diffusion** across an artificial membrane composed of pure phospholipid or of phospholipid and cholesterol (Figure 7-1). Such molecules also can diffuse across ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Few Molecules Cross Membranes by Passive Diffusion",
"token_count": 788,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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As is evident from Figure 7-1, very few molecules and no ions can cross a pure phospholipid bilayer at appreciable rates by passive diffusion. Thus transport of most molecules
#### ▲ **FIGURE 7-2 Overview of membrane transport proteins.**
Gradients are indicated by triangles with the... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Membrane Proteins Mediate Transport of Most Molecules and All Ions Across Biomembranes",
"token_count": 1958,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### **EXPERIMENTAL FIGURE 7-3 Cellular uptake of glucose mediated by GLUT proteins exhibits simple enzyme kinetics and greatly exceeds the calculated rate of glucose entry solely by passive diffusion.** The initial rate of glucose uptake (measured as micromoles per milliliter of cells ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Membrane Proteins Mediate Transport of Most Molecules and All Ions Across Biomembranes",
"token_count": 2017,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### **Transport Proteins Can Be Enriched Within Artificial Membranes and Cells**
Although transport proteins can be isolated from membranes and purified, the functional properties of these proteins can be studied only when they are associated with a membrane. Most cellular membranes contain many different types of... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Membrane Proteins Mediate Transport of Most Molecules and All Ions Across Biomembranes",
"token_count": 762,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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We turn now to the ATP-powered pumps, which transport ions and various small molecules against their concentration gradients. All ATP-powered pumps are transmembrane proteins with one or more binding sites for ATP located on the cytosolic face of the membrane. Although these proteins commonly are called ATPases, they n... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.2 ATP-Powered Pumps and the Intracellular Ionic Environment",
"token_count": 1642,
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The specific ionic composition of the cytosol usually differs greatly from that of the surrounding extracellular fluid. In virtually all cells—including microbial, plant, and animal cells—the cytosolic pH is kept near 7.2 regardless of the extracellular pH. Also, the cytosolic concentration of K<sup>+</sup> is
much h... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "ATP-Powered Ion Pumps Generate and Maintain Ionic Gradients Across Cellular Membranes",
"token_count": 971,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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In skeletal muscle cells, $Ca^{2+}$ ions are concentrated and stored in the sarcoplasmic reticulum (SR); release of stored $Ca^{2+}$ ions from the SR lumen into the cytosol causes con-
traction, as discussed in Chapter 19. A P-class Ca<sup>2+</sup> ATPase located in the SR membrane of skeletal muscle pumps Ca<sup... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Muscle Ca<sup>2+</sup> ATPase Pumps Ca<sup>2+</sup> Ions from the Cytosol into the Sarcoplasmic Reticulum",
"token_count": 1899,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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As we explain in Chapter 13, small increases in the concentration of free Ca<sup>2+</sup> ions in the cytosol trigger a variety of cellular responses. In order for Ca<sup>2+</sup> to function in intracellular signaling, the concentration of Ca<sup>2+</sup> ions free in the cytosol usually must be kept below 0.1 - 0.2 µ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Muscle Ca<sup>2+</sup> ATPase Pumps Ca<sup>2+</sup> Ions from the Cytosol into the Sarcoplasmic Reticulum",
"Header 3": "Calmodulin-Mediated Activation of Plasma-Membrane Ca<sup>2+</sup> ATPase Leads to Rapid Ca<sup>2+</sup>... |
Thus at pH 4, a primary spherical lysosome with a volume of $4.18\times10^{-15}$ ml (diameter of 0.2 $\mu$ m) will contain just 252 protons.
By themselves ATP-powered proton pumps cannot acidify the lumen of an organelle (or the extracellular space) because these pumps are *electrogenic*; that is, a net movement o... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Muscle Ca<sup>2+</sup> ATPase Pumps Ca<sup>2+</sup> Ions from the Cytosol into the Sarcoplasmic Reticulum",
"Header 3": "Calmodulin-Mediated Activation of Plasma-Membrane Ca<sup>2+</sup> ATPase Leads to Rapid Ca<sup>2+</sup>... |
Discovery of the first eukaryotic ABC protein to be recognized came from studies on tumor cells and cultured cells that exhibited resistance to several drugs with unrelated chemical structures. Such cells eventually were shown to express elevated levels of a *multidrug-resistance (MDR) transport protein* known as *MDR1... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "About 50 ABC Small-Molecule Pumps Are Known in Mammals",
"token_count": 1694,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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- Four classes of transmembrane proteins couple the energy-releasing hydrolysis of ATP with the energy-requiring transport of substances against their concentration gradient: P-, V-, and F-class pumps and ABC proteins (see Figure 7-6).
- The combined action of P-class Na<sup>+</sup>/K<sup>+</sup> ATPases in the plasma ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "About 50 ABC Small-Molecule Pumps Are Known in Mammals",
"Header 3": "ATP-Powered Pumps and the Intracellular Ionic Environment",
"token_count": 538,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"... |
In addition to ATP-powered ion pumps, which transport ions against their concentration gradients, the plasma membrane contains channel proteins that allow the principal cellular ions (Na<sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup>, and Cl<sup>-</sup>) to move through them at different rates down their concentration gra... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.3 Nongated Ion Channels and the Resting Membrane Potential",
"token_count": 1989,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### The Membrane Potential in Animal Cells Depends Largely on Resting K<sup>+</sup> Channels
The plasma membranes of animal cells contain many open K<sup>+</sup> channels but few open Na<sup>+</sup>, Cl<sup>-</sup>, or Ca<sup>2+</sup> channels. As a result, the major ionic movement across the plasma membrane is th... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.3 Nongated Ion Channels and the Resting Membrane Potential",
"token_count": 367,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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A microelectrode, constructed by filling a glass tube of extremely small diameter with a conducting fluid such as a KCl solution, is inserted into a cell in such a way that the surface membrane seals itself around the tip of the electrode. A reference electrode is placed in the bathing medium. A potentiometer connectin... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.3 Nongated Ion Channels and the Resting Membrane Potential",
"Header 3": "▲ EXPERIMENTAL FIGURE 7-14 The electric potential across the plasma membrane of living cells can be measured.",
"token_count": 430,
"source_pdf"... |
All ion channels exhibit specificity for particular ions: K<sup>+</sup> channels allow K<sup>+</sup> but not closely related Na<sup>+</sup> ions to enter, whereas Na<sup>+</sup> channels admit Na<sup>+</sup> but not K<sup>+</sup>. Determination of the three-dimensional structure of a bacterial K<sup>+</sup> channel fir... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Ion Channels Contain a Selectivity Filter Formed from Conserved Transmembrane $\\alpha$ Helices and P Segments",
"token_count": 2030,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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The technique of **patch clamping** enables workers to investigate the opening, closing, regulation, and ion conductance of a *single* ion channel. In this technique, the inward or outward movement of ions across a patch of membrane is quantified from the amount of electric current needed to maintain the membrane poten... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Patch Clamps Permit Measurement of Ion Movements Through Single Channels",
"token_count": 683,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Two inside-out patches of muscle plasma membrane were clamped at a potential of slightly less than that of the resting membrane potential. The patch electrode contained NaCl. The transient pulses of electric current in picoamperes (pA), recorded as large downward deviations (blue arrows), indicate the opening of a Na<s... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Patch Clamps Permit Measurement of Ion Movements Through Single Channels",
"Header 3": "▲ EXPERIMENTAL FIGURE 7-18 Ion flux through individual Na<sup>+</sup> channels can be calculated from patch-clamp tracings.",
"token_c... |
As mentioned earlier, two forces govern the movement of ions across selectively permeable membranes: the voltage and the ion concentration gradient across the membrane. The sum of these forces, which may act in the same direction or in opposite directions, constitutes the electrochemical gradient. To calculate the **fr... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Na<sup>+</sup> Entry into Mammalian Cells Has a Negative Change in Free Energy ( $\\Delta G$ )",
"token_count": 1190,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Besides ATP-powered pumps, cells have a second, discrete class of proteins that transport ions and small molecules, such as glucose and amino acids, against a concentration gradient. As noted previously, cotransporters use the energy stored in the electrochemical gradient of Na<sup>+</sup> or H<sup>+</sup> ions to powe... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.4 Cotransport by Symporters and Antiporters",
"token_count": 2026,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
As mentioned earlier, inhibition of the Na<sup>+</sup>/K<sup>+</sup> ATPase by the drugs ouabain and digoxin lowers the cytosolic K<sup>+</sup> concentration and, more important, increases cytosolic Na<sup>+</sup>. The resulting reduced Na<sup>+</sup> electrochemical gradient across the membrane causes the Na<sup>+</su... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.4 Cotransport by Symporters and Antiporters",
"token_count": 2010,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
For instance, transgenic tomato plants that overexpress the vacuolar $\mathrm{Na}^+/\mathrm{H}^+$ antiporter have been shown to grow, flower, and produce fruit in the presence of soil NaCl concentrations that kill wild-type plants. Interestingly, although the leaves of these transgenic tomato plants accumulate large ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "7.4 Cotransport by Symporters and Antiporters",
"token_count": 656,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Water tends to move across a semipermeable membrane from a solution of low solute concentration to one of high concentration, a process termed **osmosis**, or osmotic flow. In other words, since solutions with a high concentration of dissolved solute have a lower concentration of water, water will spontaneously move fr... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Osmotic Pressure Causes Water to Move Across Membranes",
"token_count": 1521,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
As just noted, small changes in extracellular osmotic strength cause most animal cells to swell or shrink rapidly. In contrast, frog oocytes and eggs do not swell when placed in pond water of very low osmotic strength even though their internal salt (mainly KCl) concentration is comparable to that of other cells (≈150 ... | {
"Header 1": "TRANSPORT OF IONS AND SMALL MOLECULES ACROSS CELL MEMBRANES",
"Header 2": "Aquaporins Increase the Water Permeability of Cell Membranes",
"token_count": 370,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
the water-selective gate. (c) Side view of the pore in a single aquaporin subunit in which several water molecules (red oxygens and white hydrogens) are seen within the 2-nm-long water-selective gate that separates the water filled cytosolic and extracellular vestibules. The gate contains highly conserved arginine and ... | {
"Header 1": "▲ FIGURE 7-26 Structure of the water-channel protein aquaporin. (a) Structural model of the tetrameric protein comprising four identical subunits. Each subunit forms a water channel, as seen in this end-on view from the exoplasmic surface. One of the monomers is shown with a molecular surface in which ... |
This strongly acidic medium kills many ingested pathogens and denatures many ingested proteins before they are degraded by proteolytic enzymes (e.g., pepsin) that function at acidic pH. Hydrochloric acid is secreted into the stomach by specialized epithelial cells called parietal cells (also known as oxyntic cells) in ... | {
"Header 1": "▲ FIGURE 7-26 Structure of the water-channel protein aquaporin. (a) Structural model of the tetrameric protein comprising four identical subunits. Each subunit forms a water channel, as seen in this end-on view from the exoplasmic surface. One of the monomers is shown with a molecular surface in which ... |
In the previous section, we examined how different transport proteins work together to absorb nutrients across the intestinal epithelium and to acidify the stomach. The nervous system, however, provides the most striking example of the interplay of various ion channels, transporters, and ion pumps in carrying out physi... | {
"Header 1": "▲ FIGURE 7-26 Structure of the water-channel protein aquaporin. (a) Structural model of the tetrameric protein comprising four identical subunits. Each subunit forms a water channel, as seen in this end-on view from the exoplasmic surface. One of the monomers is shown with a molecular surface in which ... |
equilibrium potential $E_{\rm Na}$ given by the Nernst equation (Equation 7-2), as would be expected if opening of voltage-gated Na<sup>+</sup> channels is responsible for generating action potentials. For example, the measured peak value of the action potential for the squid giant axon is 35 mV, which is close to th... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
The cycle of membrane depolarization, hyperpolarization, and return to the resting value that constitutes an action potential lasts 1–2 milliseconds and can occur hundreds of times a second in a typical neuron (see Figure 7-30). These cyclical changes in the membrane potential result from the sequential opening and clo... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
The generation of an action potential just described relates to the changes that occur in a small patch of the neuronal plasma membrane. At the peak of the action potential, passive spread of the membrane depolarization is sufficient to depolarize a neighboring segment of membrane. This causes a few voltage-gated $\ma... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
At time 0, an action potential (red) is at the 2-mm position on the axon; the Na+ channels at this position are open and Na<sup>+</sup> ions are flowing inward. The excess Na<sup>+</sup> ions diffuse in both directions along the inside of the membrane, passively spreading the depolarization. Because the Na+ channels at... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
Having explained how the action potential is dependent on regulated opening and closing of voltage-gated channels, we turn to a molecular dissection of these remarkable proteins. After describing the basic structure of these channels, we focus on three questions:
- How do these proteins sense changes in membrane pote... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
Sensitive electric measurements suggest that the opening of a voltage-gated Na+ or K+ channel is accompanied by the movement of 10 to 12 protein-bound positive charges from the cytosolic to the exoplasmic surface of the membrane; alternatively, a larger number of charges may move a shorter distance across the membrane.... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
An important characteristic of most voltage-gated channels is inactivation; that is, soon after opening they close spontaneously, forming an inactive channel that will not reopen until the membrane is repolarized. In the resting state, the positively charged globular balls at the N-termini of the four subunits in a vol... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
As we have seen, action potentials can move down an axon without diminution at speeds up to 1 meter per second. But even such fast speeds are insufficient to permit the complex movements typical of animals. In humans, for instance, the cell bodies of motor neurons innervating leg muscles are located in the spinal cord,... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
The myelin sheath surrounding an axon is formed from many glial cells. Each region of myelin formed by an individual glial cell is separated from the next region by an unmyelinated area of axonal membrane about 1 $\mu m$ in length called the *node of Ranvier* (or simply, node). The axonal membrane is in direct contac... | {
"Header 1": "▲ FIGURE 7-32 Depolarization of the plasma membrane due to opening of gated Na<sup>+</sup> channels. (a) In resting neurons, nongated K<sup>+</sup> channels are open, but the more numerous gated Na<sup>+</sup> channels are closed. The movement of K<sup>+</sup> ions outward establishes the inside-negati... |
Ranvier. Both of these transport proteins interact with two cytoskeletal proteins, ankyrin and spectrin, similar to those in the erythrocyte membrane (see Figure 5-31). The extracellular domain of the β1 subunit of the Na<sup>+</sup> channel also binds to the extracellular domain of Nr-CAM, a type of adhesive protein t... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
- Action potentials are sudden membrane depolarizations followed by a rapid repolarization. They originate at the axon hillock and move down the axon toward the axon terminals, where the electric impulse is transmitted to other cells via a synapse (see Figures 7-29 and 7-31).
- An action potential results from the sequ... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
As noted earlier, synapses are the junctions where neurons release a chemical neurotransmitter that acts on a postsynaptic target cell, which can be another neuron or a muscle or gland cell (see Figure 7-31). In this section, we focus on several key issues related to impulse transmission:
- How neurotransmitters are ... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
Numerous small molecules function as neurotransmitters at various synapses. With the exception of **acetylcholine**, the
$$\begin{array}{c} O \\ \parallel \\ \mathrm{CH_3-C-O-CH_2-CH_2-N^+-(CH_3)_3} \\ \mathbf{Acetylcholine} \end{array}$$
$$\begin{array}{cccccccccccccccccccccccccccccccccccc$$
Glycine
$$\begin{a... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
Neurotransmitters are released by **exocytosis**, a process in which neurotransmitter-filled synaptic vesicles fuse with the axonal membrane, releasing their contents into the synaptic cleft. The exocytosis of neurotransmitters from synaptic vesicles involves vesicle-targeting and fusion events similar to those that oc... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
Following their release from a presynaptic cell, neurotransmitters must be removed or destroyed to prevent continued stimulation of the postsynaptic cell. Signaling can be terminated by diffusion of a transmitter away from the synaptic cleft, but this is a slow process. Instead, one of two more rapid mechanisms termina... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
The acetylcholine receptor from skeletal muscle is a pentameric protein with a subunit composition of $\alpha_2\beta\gamma\delta$ . The $\alpha,$ $\beta,$ $\gamma,$ and $\delta$ subunits have considerable sequence homology; on average, about 35–40 percent of the residues in any two subunits are similar. The co... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
At the neuromuscular junction, virtually every action potential in the presynaptic motor neuron triggers an action potential in the postsynaptic muscle cell. The situation at synapses between neurons, especially those in the brain, is much more complex because the postsynaptic neuron commonly receives signals from many... | {
"Header 1": "▲ FIGURE 7-40 Conduction of action potentials in myelinated axons. Because voltage-gated Na<sup>+</sup> channels are localized to the axonal membrane at the nodes of Ranvier, the influx of Na<sup>+</sup> ions associated with an action potential can occur only at nodes. When an action potential is gener... |
Whether a neuron generates an action potential in the axon hillock depends on the balance of the timing, amplitude, and localization of all the various inputs it receives; this signal computation differs for each type of neuron. In a sense, each neuron is a tiny computer that averages all the receptor activations and e... | {
"Header 1": "■ EXPERIMENTAL FIGURE 7-48 Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. Arrival of each action potential at the synapse causes a small cha... |
Perhaps the most difficult questions concern the formation of specific synapses within the nervous system; that is, how does a neuron "know" to synapse with one type of cell and not another? Ongoing research on the development of the nervous system, which we briefly discuss in Chapter 15, is beginning to provide more c... | {
"Header 1": "■ EXPERIMENTAL FIGURE 7-48 Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. Arrival of each action potential at the synapse causes a small cha... |
Based on the data shown in the following figure, does BNP1-dependent transport display the expected properties? Why are the chosen amino acids the logical choices for potential competitors?
Effect of amino acid competitors and valinomycin plus nigericin (V N) on BNP1 transport.
**c.**... | {
"Header 1": "■ EXPERIMENTAL FIGURE 7-48 Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. Arrival of each action potential at the synapse causes a small cha... |
*Nature* **414**:43–48.
#### Cotransport by Symporters and Antiporters
Alper, S. L., M. N. Chernova, and A. K. Stewart. 2001. Regulation of $Na^+$ -independent $Cl^-/HCO_3^-$ exchangers by pH. *J. Pancreas* 2:171–175.
Barkla, B., and O. Pantoja. 1996. Physiology of ion transport across the tonoplast of higher ... | {
"Header 1": "■ EXPERIMENTAL FIGURE 7-48 Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. Arrival of each action potential at the synapse causes a small cha... |
Amara, S. G., and M. J. Kuhar. 1993. Neurotransmitter transporters: recent progress. *Ann. Rev. Neurosci.* 16:73–93.
Bajjalieh, S. M., and R. H. Scheller. 1995. The biochemistry of neurotransmitter secretion. *J. Biol. Chem.* **270**:1971–1974.
Betz, W., and J. Angleson. 1998. The synaptic vesicle cycle. Ann. Rev. ... | {
"Header 1": "■ EXPERIMENTAL FIGURE 7-48 Incoming signals must reach the threshold potential to trigger an action potential in a postsynaptic cell. In this example, the presynaptic neuron is generating about one action potential every 4 milliseconds. Arrival of each action potential at the synapse causes a small cha... |
Computer-generated model of a section of a mitochondrion from chicken brain, based on a three-dimensional electron tomogram. [T. Frey and C. Mannella, 2000, Trends Biochem. Sci. 25:319.]
he most important molecule for capturing and transferring free energy in biological systems is **adenosine triphosphate**, or **ATP... | {
"Header 1": "8",
"Header 2": "CELLULAR ENERGETICS",
"token_count": 1751,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
membrane surface facing a shaded area is a cytosolic face; the surface facing an unshaded area is an exoplasmic face. Note that the cytosolic face of the bacterial plasma membrane, the matrix face of the inner mitochondrial membrane, and the stromal face of the thylakoid membrane are all equivalent. During electron tra... | {
"Header 1": "8",
"Header 2": "▲ FIGURE 8-2 Membrane orientation and the direction of proton movement during chemiosmotically coupled ATP synthesis in bacteria, mitochondria, and chloroplasts. The",
"token_count": 226,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Membrane surfaces facing a shaded area are cytosolic faces; surfaces facing an unshaded area are exoplasmic faces. Endocytosis of a bacterium by an ancestral eukaryotic cell would generate an organelle with two membranes, the outer membrane derived from the eukaryotic plasma membrane and the inner one from the bacteria... | {
"Header 1": "8",
"Header 2": "▲ FIGURE 8-2 Membrane orientation and the direction of proton movement during chemiosmotically coupled ATP synthesis in bacteria, mitochondria, and chloroplasts. The",
"Header 3": "▲ FIGURE 8-3 Evolutionary origin of mitochondria and chloroplasts according to endosymbiont hypothesi... |
The complete aerobic oxidation of each molecule of glucose yields 6 molecules of CO<sub>2</sub> and is coupled to the synthesis of as many as 30 molecules of ATP:
$$\begin{array}{c} C_6 H_{12} O_6 + 6 \ O_2 + 30 \ P_i^{\, 2-} + 30 \ ADP^{3-} + 30 \ H^+ \\ \longrightarrow 6 \ CO_2 + 30 \ ATP^{4-} + 36 \ H_2 O \end{arr... | {
"Header 1": "8",
"Header 2": "8.1 Oxidation of Glucose and Fatty Acids to CO<sub>2</sub>",
"token_count": 310,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
A set of 10 water-soluble cytosolic enzymes catalyze the reactions constituting the *glycolytic pathway*, in which one molecule of glucose is converted to two molecules of pyruvate (Figure 8-4). All the metabolic intermediates between glucose and pyruvate are water-soluble phosphorylated compounds.
Four molecules of ... | {
"Header 1": "8",
"Header 2": "Cytosolic Enzymes Convert Glucose to Pyruvate During Glycolysis",
"token_count": 2041,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
(a)
#### **Mitochondria Possess Two Structurally and Functionally Distinct Membranes**
Mitochondria are among the larger organelles in the cell, each one being about the size of an *E. coli* bacterium. Most eukaryotic cells contain many mitochondria, which collectively can occupy as much as 25 percent of the volu... | {
"Header 1": "8",
"Header 2": "Cytosolic Enzymes Convert Glucose to Pyruvate During Glycolysis",
"token_count": 257,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
#### ▲ **FIGURE 8-6 Internal structure of a mitochondrion.**
(a) Schematic diagram showing the principal membranes and compartments. The cristae form sheets and tubes by invagination of the inner membrane and connect to the inner membrane through relatively small uniform tubular structures called *crista junctions.* ... | {
"Header 1": "8",
"Header 2": "Cytosolic Enzymes Convert Glucose to Pyruvate During Glycolysis",
"Header 3": "Intermembrane space Outer membrane Inner membrane Matrix Cristae junctions Cristae 1~2 m 0.1~0.5 m",
"token_count": 663,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Pyruvate is converted to acetyl CoA with the formation of NADH, and fatty acids (attached to CoA) are also converted to acetyl CoA with formation of NADH and FADH. Oxidation of acetyl CoA in the citric acid cycle generates NADH and FADH $_2$ . Stage 2: Electrons from these reduced coenzymes are transferred via electron... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
Immediately after pyruvate is transported from the cytosol across the mitochondrial membranes to the matrix, it reacts with coenzyme A, forming $CO_2$ and the intermediate **acetyl CoA** (Figure 8-8). This reaction, catalyzed by *pyruvate dehydrogenase*, is highly exergonic ( $\Delta G^{\circ\prime}=-8.0~\text{kcal/m... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
For aerobic oxidation to continue, the NADH produced during glycolysis in the cytosol must be oxidized to NAD $^+$ . As with NADH generated in the mitochondrial matrix, electrons from cytosolic NADH are ultimately transferred to $\mathrm{O}_2$ via the respiratory chain, concomitant with the generation of
a proton-m... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
Fatty acids are stored as **triacylglycerols**, primarily as droplets in adipose (fat-storing) cells. In response to hormones such as adrenaline, triacylglycerols are hydrolyzed in the cytosol to free fatty acids and glycerol:
$$\begin{array}{c|c} & O \\ & & \\ & & \\ & & \\ & CH_3-(CH_2)_n-C-O-CH_2 \\ & & \\ & O \\ ... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
This electron movement is coupled to generation of a proton-motive force that is used to power ATP synthesis as described previously for the oxidation of pyruvate (see Figure 8-7).
#### Peroxisomal Oxidation of Fatty Acids Generates No ATP
Mitochondrial oxidation of fatty acids is the major source of ATP in mammali... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
All enzyme-catalyzed reactions and metabolic pathways are regulated by cells so as to produce the needed amounts of metabolites but not an excess. The primary function of the oxidation of glucose to $\mathrm{CO}_2$ via the glycolytic pathway, the pyruvate dehydrogenase reaction, and the citric acid cycle is to produc... | {
"Header 1": "▲ FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P₁ (purple) into the mat... |
2,6-bisphosphate from fructose 6-phosphate, and its phosphatase activity catalyzes the reverse reaction. Insulin, which is released by the pancreas when blood glucose levels are high, promotes PFK2 kinase activity and thus stimulates glycolysis. At low blood glucose, glucagon is released by the pancreas and promotes PF... | {
"Header 1": "▲ FIGURE 8-12 Allosteric control of glucose metabolism in the cytosol at the level of fructose 6-phosphate. The key regulatory enzyme in glycolysis, phosphofructokinase-1, is allosterically activated by AMP and fructose 2,6-bisphosphate, which are elevated when the cell's energy stores are low. The enz... |
As noted in the previous section, most of the free energy released during the oxidation of glucose to $CO_2$ is retained in the reduced coenzymes NADH and FADH<sub>2</sub> generated during glycolysis and the citric acid cycle. During respiration, electrons are released from NADH and FADH<sub>2</sub> and eventually ar... | {
"Header 1": "▲ FIGURE 8-12 Allosteric control of glucose metabolism in the cytosol at the level of fructose 6-phosphate. The key regulatory enzyme in glycolysis, phosphofructokinase-1, is allosterically activated by AMP and fructose 2,6-bisphosphate, which are elevated when the cell's energy stores are low. The enz... |
As we've seen, the proton-motive force (pmf) is the sum of a transmembrane proton concentration (pH) gradient and electric potential, or voltage gradient. The relative contribution of the two components to the total pmf depends on the permeability of the membrane to ions other than H<sup>+</sup>. A significant voltage ... | {
"Header 1": "▲ FIGURE 8-12 Allosteric control of glucose metabolism in the cytosol at the level of fructose 6-phosphate. The key regulatory enzyme in glycolysis, phosphofructokinase-1, is allosterically activated by AMP and fructose 2,6-bisphosphate, which are elevated when the cell's energy stores are low. The enz... |
We now examine more closely the energetically favored movement of electrons from NADH and $FADH_2$ to the final electron acceptor, $O_2$ . In respiring mitochondria, each NADH molecule releases two electrons to the respiratory chain; these electrons ultimately reduce one oxygen atom (half of an $O_2$ molecule), fo... | {
"Header 1": "▲ FIGURE 8-12 Allosteric control of glucose metabolism in the cytosol at the level of fructose 6-phosphate. The key regulatory enzyme in glycolysis, phosphofructokinase-1, is allosterically activated by AMP and fructose 2,6-bisphosphate, which are elevated when the cell's energy stores are low. The enz... |
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