(BQ) Part 2 book “Harper’s illustrated biochemistry” has contents: Biochemical case histories, the biochemistry of aging, white blood cells, red blood cells, plasma proteins & immunoglobulins, muscle & the cytoskeleton, the extracellular matrix, clinical biochemistry, hormone action & signal transduction,… and other contents.
SECTION VIII Biochemistry of Extracellular & Intracellular Communication CHAPTER 40 Membranes: Structure & Function P Anthony Weil, PhD OBJECTIVES After studying this chapter, you should be able to: Know that biologic membranes are mainly composed of a lipid bilayer and associated proteins and glycoproteins The major lipids are phospholipids, cholesterol, and glycosphingolipids Appreciate that membranes are asymmetric, dynamic structures containing a mixture of integral and peripheral proteins Describe the widely accepted fluid mosaic model of membrane 1120 structure Understand the concepts of passive diffusion, facilitated diffusion, active transport, endocytosis, and exocytosis Recognize that transporters, ion channels, the Na+ − K+-ATPase, receptors, and gap junctions are important participants in membrane function Be aware that a variety of disorders result from abnormalities of membrane structure and function, including familial hypercholesterolemia, cystic fibrosis, hereditary spherocytosis, among others BIOMEDICAL IMPORTANCE Membranes are dynamic, highly fluid structures consisting of a lipid bilayer and associated proteins Plasma membranes form closed compartments around the cytoplasm to define cell boundaries The plasma membrane has selective permeabilities and acts as a barrier, thereby maintaining differences in composition between the inside and outside of the cell Selective membrane molecular permeability is generated through the action of specific transporters and ion channels The plasma membrane also exchanges material with the extracellular environment by exocytosis and endocytosis, and there are special areas of membrane structure—gap junctions—through which adjacent cells may communicate by exchanging material In addition, the plasma membrane plays key roles in cell–cell interactions and in transmembrane signaling Membranes also form specialized compartments within the cell Such intracellular membranes help shape many of the morphologically distinguishable structures (organelles), for example, mitochondria, endoplasmic reticulum (ER), Golgi, secretory granules, lysosomes, and the nucleus Membranes localize enzymes, function as integral elements in excitation-response coupling, and provide sites of energy transduction, such as in photosynthesis in plants (chloroplasts) and oxidative phosphorylation (mitochondria) Changes in membrane components can affect water balance and ion flux, and therefore many processes within the cell Specific deficiencies or alterations of certain membrane components (eg, caused by mutations in genes encoding membrane proteins) lead to a variety of diseases (see Table 40–7) In short, normal cellular function critically depends on normal membranes 1121 MAINTENANCE OF A NORMAL INTRA- & EXTRACELLULAR ENVIRONMENT IS FUNDAMENTAL TO LIFE Life originated in an aqueous environment; enzyme reactions, cellular and subcellular processes have therefore evolved to work in this milieu, encapsulated within a cell The Body’s Internal Water Is Compartmentalized Water makes up about 60% of the lean body mass of the human body and is distributed in two large compartments Intracellular Fluid (ICF) This compartment constitutes two-thirds of total body water and provides a specialized environment for the cell to (1) make, store, and utilize energy; (2) to repair itself; (3) to replicate; and (4) to perform cell-specific functions Extracellular Fluid (ECF) This compartment contains about one-third of total body water and is distributed between the plasma and interstitial compartments The extracellular fluid is a delivery system It brings to the cells nutrients (eg, glucose, fatty acids, and amino acids), oxygen, various ions and trace minerals, and a variety of regulatory molecules (hormones) that coordinate the functions of widely separated cells Extracellular fluid removes CO2, waste products, and toxic or detoxified materials from the immediate cellular environment The Ionic Compositions of Intracellular & Extracellular Fluids Differ Greatly As illustrated in Table 40–1, the internal environment is rich in K+ and Mg2+, and phosphate is its major inorganic anion The cytosol of cells contains a high concentration of protein that acts as a major intracellular buffer Extracellular fluid is characterized by high Na+ and Ca2+ content, and Cl− is the major anion These ionic differences are maintained due to various membranes found in cells These membranes have unique lipid 1122 and protein compositions A fraction of the protein constituents of membrane proteins are specialized to generate and maintain the differential ionic compositions of the extra- and intracellular compartments TABLE 40–1 Comparison of the Mean Concentrations of Various Molecules Outside and Inside a Mammalian Cell MEMBRANES ARE COMPLEX STRUCTURES COMPOSED OF LIPIDS, PROTEINS, & CARBOHYDRATE-CONTAINING MOLECULES We shall mainly discuss the membranes present in eukaryotic cells, although many of the principles described also apply to the membranes of prokaryotes The various cellular membranes have different lipid and protein compositions The ratio of protein to lipid in different membranes is presented in Figure 40–1, and is responsible for the many divergent functions of cellular organelles Membranes are sheet-like enclosed structures consisting of an asymmetric lipid bilayer with distinct inner and outer surfaces or leaflets These structures and surfaces are proteinstudded, sheet-like, noncovalent assemblies that form spontaneously in aqueous environments due to the amphipathic nature of lipids and the proteins contained within the membrane 1123 FIGURE 40–1 Membrane protein content is highly variable The amount of proteins equals or exceeds the quantity of lipid in nearly all membranes The outstanding exception is myelin, an electrical insulator found on many nerve fibers The Major Lipids in Mammalian Membranes Are Phospholipids, Glycosphingolipids & Cholesterol Phospholipids Of the two major phospholipid classes present in membranes, phosphoglycerides are the more common and consist of a glycerolphosphate backbone to which are attached two fatty acids in ester linkages and an alcohol (Figure 40–2) The fatty acid constituents are usually 1124 even-numbered carbon molecules, most commonly containing 16 or 18 carbons They are unbranched and can be saturated or unsaturated with one or more double bonds The simplest phosphoglyceride is phosphatidic acid, a 1,2-diacylglycerol 3-phosphate, a key intermediate in the formation of other phosphoglycerides (see Chapter 24) In most phosphoglycerides present in membranes, the 3-phosphate is esterified to an alcohol such as choline, ethanolamine, glycerol, inositol, or serine (see Chapter 21) Phosphatidylcholine is generally the major phosphoglyceride by mass in the membranes of human cells FIGURE 40–2 A phosphoglyceride showing the fatty acids (R1 and R2), glycerol, and a phosphorylated alcohol component Saturated fatty acids are usually attached to carbon of glycerol, and unsaturated fatty acids to carbon In phosphatidic acid, R3 is hydrogen The second major class of phospholipids comprises sphingomyelin (see Figure 21–11), a phospholipid that contains a sphingosine rather than a glycerol backbone A fatty acid is attached by an amide linkage to the amino group of sphingosine, forming ceramide When the primary hydroxyl group of sphingosine is esterified to phosphorylcholine, sphingomyelin is formed As the name suggests, sphingomyelin is prominent in myelin sheaths Glycosphingolipids The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide GSLs include galactosyl- and glucosyl-ceramides (cerebrosides) and the gangliosides (see structures in Chapter 21), and are mainly located in the plasma membranes of cells, displaying their sugar components to the exterior of the cell 1125 Sterols The most common sterol in the membranes of animal cells is cholesterol (see Chapter 21) The majority of cholesterol resides within plasma membranes, but smaller amounts are found within mitochondrial, Golgi complex, and nuclear membranes Cholesterol intercalates among the phospholipids of the membrane, with its hydrophilic hydroxyl group at the aqueous interface and the remainder of the molecule buried within the lipid bilayer leaflet From a nutritional viewpoint, it is important to know that cholesterol is not present in plants Lipids can be separated from one another and quantified by techniques such as column, thin-layer, and gas-liquid chromatography and their structures established by mass spectrometry and other techniques (see Chapter 4) Membrane Lipids Are Amphipathic All major lipids in membranes contain both hydrophobic and hydrophilic regions and are therefore termed amphipathic If the hydrophobic region were separated from the rest of the molecule, it would be insoluble in water but soluble in organic solvents Conversely, if the hydrophilic region were separated from the rest of the molecule, it would be insoluble in organic solvents but soluble in water The amphipathic nature of a phospholipid is represented in Figure 40–3 and also Figure 21–24 Thus, the polar head groups of the phospholipids and the hydroxyl group of cholesterol interface with the aqueous environment; a similar situation applies to the sugar moieties of the GSLs (see below) 1126 FIGURE 40–3 Diagrammatic representation of a phospholipid or other membrane lipid The polar head group is hydrophilic, and the hydrocarbon tails are hydrophobic or lipophilic The fatty acids in the tails are saturated (S) or unsaturated (U); the former is usually attached to carbon of glycerol and the latter to carbon (see Figure 40–2) Note the kink in the tail of the unsaturated fatty acid (U), which is important in conferring increased membrane fluidity The S-U phospholipid on the left contains the C16 saturated lipid palmitic acid, and the monounsaturated C18 lipid cis-oleic acid; both are esterified to glycerol (see Figure 40-2) The S-S phospholipid schematized on the right contains the C16 saturated lipid palmitic acid and the saturated C18 lipid, stearic acid Saturated fatty acids form relatively straight tails, whereas unsaturated fatty acids, which generally exist in the cis form in membranes, form “kinked” tails (Figure 40–3; see also Figures 21–1, 21–6) As the number of double bonds within the lipid side chains increase, the number of kinks in the tails increases As a consequence, the membrane lipids become less tightly packed and the membrane more fluid The problem caused by the presence of trans fatty acids in membrane lipids is described in Chapter 21 1127 Detergents are amphipathic molecules that are important in biochemistry as well as in the household The molecular structure of a detergent is not unlike that of a phospholipid Certain detergents are widely used to solubilize and purify membrane proteins The hydrophobic end of the detergent binds to hydrophobic regions of the proteins, displacing most of their bound lipids The polar end of the detergent is free, bringing the proteins into solution as detergent-protein complexes, usually also containing some residual lipids Membrane Lipids Form Bilayers The amphipathic character of phospholipids suggests that the two regions of the molecule have incompatible solubilities However, in a solvent such as water, phospholipids spontaneously organize themselves into micelles (Figure 40–4 and Figure 21–24), an assembly that thermodynamically satisfies the solubility requirements of the two chemically distinct regions of these molecules Within the micelle the hydrophobic regions of the amphipathic phospholipids are shielded from water, while the hydrophilic polar groups are immersed in the aqueous environment Micelles are usually relatively small in size (eg, ~200 nm) and consequently are limited in their potential to form membranes Detergents commonly form micelles FIGURE 40–4 Diagrammatic cross-section of a micelle The polar head groups are bathed in water, whereas the hydrophobic hydrocarbon tails are 1128 surrounded by other hydrocarbons and thereby protected from water Micelles are relatively small (compared with lipid bilayers) spherical structures Phospholipids and similar amphipathic molecules can form another structure, the bimolecular lipid bilayer, which also satisfies the thermodynamic requirements of amphipathic molecules in an aqueous environment Bilayers are the key structures in biologic membranes Bilayers exist as sheets wherein the hydrophobic regions of the phospholipids are sequestered from the aqueous environment, while the hydrophilic, charged portions are exposed to water (Figure 40–5 and Figure 21–24) The ends or edges of the bilayer sheet can be eliminated by folding the sheet back on itself to form an enclosed vesicle with no edges The closed bilayer provides one of the most essential properties of membranes The lipid bilayer is impermeable to most water-soluble molecules since such charged molecules would be insoluble in the hydrophobic core of the bilayer The self-assembly of lipid bilayers is driven by the hydrophobic effect, which describes the tendency of nonpolar molecules to self-associate in an aqueous environment, while in the process excluding H2O When lipid molecules come together in a bilayer, the entropy of the surrounding solvent molecules increases due to the release of immobilized water FIGURE 40–5 Diagram of a section of a bilayer membrane formed from phospholipids The unsaturated fatty acid tails are kinked and lead to more spacing between the polar head groups, and hence to more room for movement This in turn results in increased membrane fluidity Two questions arise from consideration of the information described above First, how many biologically important molecules are lipid-soluble 1129 tumor viruses, 684–685, 684t, 686f, 703 tumors benign, 681 malignant See cancer turnover, protein, 84, 269–270 turnover number, 75 turns, in proteins, 36, 37f twin lamb disease, 215, 244 twisted gastrulation (TWSG1), 635 two-dimensional electrophoresis, protein purity assessment with, 26, 27f two-hybrid interaction test, 447, 449f TWSG1 (twisted gastrulation 1), 635 TxA2 See thromboxane A2 TXs See thromboxanes type leukocyte adhesion deficiency, 658–659 type diabetes, 172 type A response, in gene expression, 410–411, 410f type B response, in gene expression, 410f, 411 type C response, in gene expression, 410f, 411 type I collagen, 604–605, 605t type I hyperprolinemia, 282, 282f type I tyrosinemia, 286, 287f type II collagen, 607, 608f type II hyperprolinemia, 282, 282f, 285f, 286 type II tyrosinemia, 286, 287f type IV collagen, 595–596 type IX collagen, 595 type V collagen, 604 type VII collagen, 596 tyrosinase, copper in, 98–100 tyrosine, 15t–16t carbon skeleton catabolism of, 286, 287f hormone synthesis from, 483, 484f, 491–492, 491f, 493f specialized products of, 300, 302f synthesis of, 266, 267f ultraviolet light absorption by, 20, 20f tyrosine aminotransferase, 286, 287f 2009 tyrosine hydroxylase, 491, 491f tyrosine kinases, inhibitors of, 701 tyrosinosis, 286, 287f tyrosinyl-tRNA, 407, 407f U UAS (upstream activator sequence), 427 ubiquinone See coenzyme Q ubiquitin protein degradation dependent on, 270–271, 270f, 271f structure of, 270, 270f ubiquitin and protein degradation, 584–585, 585f ubiquitin-proteasome pathway, enzyme degradation by, 84–85, 270–271, 270f, 271f UCP1 (uncoupling protein 1), 247, 247f UDPGal (uridine diphosphate galactose), 187–188, 189f UDPGal 4-epimerase, 187–188, 189f UDPGlc See uridine diphosphate glucose UDPGlc dehydrogenase, in uronic acid pathway, 186–187, 187f UDPGlc pyrophosphorylase in glycogenesis, 164, 165f in uronic acid pathway, 186–187, 187f ulcers, 519, 555 ultimate carcinogens, 684 ultraviolet light (UV), 712, 713f amino acid absorption of, 20, 20f carcinogenic effect of, 683, 683t DNA damage caused by, 370f, 370t nucleotide absorption of, 321 UMP (uridine monophosphate), 322f, 322t unambiguity, of genetic code, 394, 394t unconjugated hyperbilirubinemia, 313t, 314 uncouplers, 123–124, 525 uncoupling protein (UCP1), 247, 247f undernutrition, 519, 524–525, 524f unequal crossover, 359, 360f unesterified fatty acids See free fatty acids 2010 unfolded protein response (UPR), 584 Union of Biochemistry (IUB), enzyme nomenclature system of, 57 uniport systems, 468, 468f unipotent stem cells, 646 unique-sequence (nonrepetitive) DNA, 357 universality of genetic code, 394t, 395 unsaturated fatty acids, 196, 196f, 197–198, 197t cis double bonds in, 198, 198f dietary, cholesterol levels affected by, 257 eicosanoids formed from, 216, 224, 225f, 226f essential, 222, 222f abnormal metabolism of, 226 deficiency of, 224 prostaglandin production and, 216 in membranes, 461–462, 461f, 462f oxidation of, 210, 211f structures of, 222f synthesis of, 223–224, 223f UPR (unfolded protein response), 584 upstream activator sequence (UAS), 427 uracil, 322t, 337f base pairing in RNA, 342, 343f deoxyribonucleosides of, in pyrimidine synthesis, 332–333 in RNA synthesis, 375 uraciluria-thyminuria, 327–328, 336 urate, as antioxidant, 204 urea laboratory tests for, 566 metabolic pathways of, 131, 133 nitrogen excretion as, 272, 275, 275f permeability coefficient of, 463f synthesis of, 272–273, 272f, 273f, 275–276, 275f active enzymes, 722t defects of, 276–278, 277t regulation of, 276 urease, transition metals in, 97, 97f ureotelic animals, 272 2011 uric acid, 321, 323f fructose effects on, 189–190 nitrogen excretion as, 272 purine catabolism to, 334, 335f uricase, 334 uricemia, 336t uricotelic animals, 272 uridine, 321f, 322t, 333 uridine diphosphate galactose (UDPGal), 187–188, 189f uridine diphosphate glucose (UDPGlc) in glycogenesis, 164–165, 165f in uronic acid pathway, 186–187, 187f uridine monophosphate (UMP), 322f, 322t uridyl transferase, deficiency of, 191 urinalysis, 566 urine bilirubin in, 313, 315, 315t glucose in, 180 myoglobin in, 54 urobilinogen in, 315, 315t xylulose in, 189 urine samples, 563 urobilinogen, 313, 315, 315t urobilins, 313 urocanic aciduria, 282 urokinase, 678f, 679 uronic acid, 599 uronic acid pathway deficiency of, 182 disruption of, 189 reactions of, 186–187, 187f uronic acids, in glycosaminoglycans, 147 uroporphyrinogen decarboxylase, 307, 307f, 308f, 309f, 310t uroporphyrinogen I, in heme synthesis, 306, 307f, 308f, 309f uroporphyrinogen I synthase, 306, 307f, 308f, 309f deficiency in, 310, 310t uroporphyrinogen III, in heme synthesis, 306–307, 307f, 308f, 309f 2012 uroporphyrinogen III synthase, 306, 307f, 308f, 309f deficiency in, 310, 310t UV See ultraviolet light V vaccines, anticancer, 703 valence states, of transition metals, 93, 94f, 94t, 95 valeric acid, 197t validity, of laboratory tests, 561–563, 561f, 562f, 563t valine, 15t carbon skeleton catabolism of, 288, 290, 292f, 293, 293f, 293t synthesis of, 266–267 valinomycin, 125, 471–472 valproic acid, 690 van der Waals forces, 8, 8f, 339–340 vanadium absorption of, 101 human requirement for, 93, 93t multivalent states of, 93, 94f, 94t physiologic roles of, 100–101 variable numbers of tandem repeats (VNTRs), 445, 549 variant form of Creutzfeldt-Jakob disease (vCJD), 42 vascular endothelial growth factor (VEGF), 697 vasodilators, 611, 622–623, 624f vCJD (variant form of Creutzfeldt-Jakob disease), 42 vector cloning, 436–437, 437t VEGF (vascular endothelial growth factor), 697 velocity, enzyme See initial velocity; maximal velocity very-low-density lipoproteins (VLDLs), 133, 138, 237t atherosclerosis and, 257 fatty liver and, 244 fructose effects on, 186, 188f, 189–190 hepatic secretion of, 242–243, 243f in ketogenesis regulation, 214 in lipid transport, 236–237 metabolism of, 240–241, 240f remnants, 241, 254 2013 in triacylglycerol transport, 238–239, 239f, 240f vesicles in cell-cell communication, 476–478, 477f coat proteins and, 583, 586–587, 586t, 587f in endocytosis, 474 extracellular, 476–478, 477f processing within, 588 secretory, 574, 575f synaptic, 587 targeting of, 587, 587f transport See transport vesicles types and functions, 586t vi See initial velocity Villefranche classification, 595, 596t vimentins, 625, 625t vinblastine, 625 viral RNA–dependent DNA polymerase, 344 viral SV40 enhancer, 421, 422f viruses chromosomal integration with, 359–360, 360f cyclophilins in, 42 glycans in binding of, 555 host cell protein synthesis by, 405–406, 406f receptor-mediated endocytosis and, 475 RNA in, 344 tumor, 684–685, 684t, 686f, 703 vision, vitamin A function in, 529, 530f vitamin A (retinol) deficiency of, 528t, 530 functions of, 528t, 529–530, 530f structure of, 529, 529f toxicity of, 530 vitamin B complex citric acid cycle need for, 153 prosthetic groups, cofactors, and coenzymes derived from, 58, 58f vitamin B1 (thiamin) 2014 citric acid cycle need for, 153 coenzymes derived from, 58 deficiency of, 161, 163, 528t, 534 functions of, 528t, 533–534 pentose phosphate pathway need for, 185 structure of, 533, 533f vitamin B2 (riboflavin) citric acid cycle need for, 153 coenzymes derived from, 58 deficiency of, 42, 528t, 534 flavin groups formed from, 112, 114 functions of, 528t, 534 measurement of, 189 vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) in aminotransferases, 273, 273f, 535 deficiency of, 288, 290f, 528t, 535 functions of, 528t, 535 structure of, 535, 535f toxicity of, 535 vitamin B12 (cobalamin) absorption of, 101, 536 cobalt in, 98 deficiency of, 528t, 536–538, 536f functions of, 528t, 536, 536f structure of, 536, 536f vitamin C (ascorbic acid) as antioxidant, 204, 544, 544f in bile acid synthesis, 256f in collagen synthesis, 43 deficiency of, 43, 263, 266, 528t, 540, 596 functions of, 528t, 539 higher intakes of, 540 human requirement for, 182, 186 iron absorption and, 523–524 as pro-oxidant, 544, 544t structure of, 539, 539f 2015 vitamin D (calciferol), 528 as calcitriol precursor, 489 calcium absorption and, 523 in calcium homeostasis, 531 cholesterol as precursor for, 249 deficiency of, 528t, 531–532 ergosterol as precursor for, 203, 203f functions of, 528t hormone nature of, 530–531, 531f synthesis and metabolism of, 530–531, 531f toxicity of, 532 vitamin D3 (cholecalciferol), 530, 531f as antioxidant, 203 formation and hydroxylation of, 489–491, 490f vitamin D–binding protein, 490 vitamin E (tocopherols, tocotrienols) as antioxidant, 204, 532, 544, 544f deficiency of, 528t, 532 fatty liver and, 244 functions of, 528t, 532 as pro-oxidant, 545 structure of, 532, 532f vitamin K deficiency of, 528t, 533 functions of, 528t, 532–533, 533f structure of, 532–533, 533f vitamin K–dependent carboxylation, of coagulation factors, 677–678 vitamins biomedical importance of, 527 digestion and absorption of, 523–524 for health maintenance, laboratory tests for, 564–565 lipid- (fat-) soluble, 196 lipid-soluble or water-soluble classification of, 527, 528t nutritional requirements for, 527–528 VLDL receptor, 238, 240 VLDLs See very-low-density lipoproteins 2016 Vmax See maximal velocity VNTRs (variable numbers of tandem repeats), 445, 549 voltage-gated channels, 470, 471, 471f, 618 voltage-gated K+ channel (HvAP), 471, 471f von Gierke disease, 166, 167t, 335 von Willebrand disease, 585t, 655, 678 von Willebrand factor, 678 in platelet aggregation, 670, 671f vorinostat, 690 v-SNARE proteins, 586–588, 587f W Warburg effect, 695–696, 697f, 698t warfarin, 532–533 drug interactions of, 557 mechanism of, 677–678 water as biologic solvent, 6–7, 7f biomedical importance of, biomolecule interactions with, 7–8, 7t, 8f body compartmentalization of, 460, 460t dipole formation by, 6–7, 7f dissociation of, 9–10 for health maintenance, hydrogen bonding of, 7, 7f hydrogen ions in, 9–13, 12f, 13t hydrolysis reactions of, as nucleophile, 8–10 permeability coefficient of, 463f pH of, 10 respiratory chain production of, 120–121 tetrahedral geometry of, 6, 7f water channels, 472 water-miscible lipoproteins, 236 water-soluble hormones, 482, 483t water-soluble molecules, 462 water-soluble vitamins, 527, 528t 2017 Watson-Crick base pairing, 339, 340f waxes, 196 weak acids amino acids as, 18–20, 19f, 20t buffering actions of, 12–13, 12f dissociation of, 10–12 as functional groups, 11–12 Henderson-Hasselbalch equation describing behavior of, 12, 12f medium properties affecting, 13 molecular structure effects on, 13, 13t pKa of, 11–13, 12f, 13t, 19 weak bases buffering actions of, 12–13, 12f dissociation of, 10–12 wear and tear theories of aging free radicals, 710, 712 hydrolytic reactions, 708–709, 709f mitochondria and, 710, 712 molecular repair mechanisms and, 713–715 protein glycation, 712–713, 714f reactive oxygen species, 709–710, 710f, 711f ultraviolet radiation, 712, 713f weight loss, low carbohydrate diets for, 181 Wernicke encephalopathy, 534 Western protein blot procedure, 438, 439f white blood cells biomedical importance of, 656 integrins in, 658–659, 659t multiple types of, 656–657, 657f phagocytosis, 474, 656, 657, 659–661, 659f, 660t production regulation of, 657 white thrombus, 670 Williams-Beuren syndrome, 596 Wilson disease, 298, 478t, 627, 634 wobble, 396 X 2018 xanthine, 321, 323f xanthine oxidase, 112 deficiency of, hypouricemia and, 335 molybdenum in, 100 xanthurenate, 288, 290f X-chromosome pair, 354 xenobiotics biomedical importance of, 556 metabolism of acetylation and methylation, 558–559 conjugation, 558 hydroxylation by cytochrome P450, 556–558 toxic, immunologic, and carcinogenic effects of, 559, 559f types of, 556 xerophthalmia, 530 X-linked disorders, 445 x-ray crystallography, 39–40 x-rays, carcinogenic effect of, 683, 683t xylose, 144f, 144t, 548t xylulose, 144f, 144t, 189 xylulose 5- phosphate, 185 Y YAC (yeast artificial chromosome) vector, 437, 437t yeast, fermentation by cell-free extract of, 1–2 yeast artificial chromosome (YAC) vector, 437, 437t yeast Flp recombinase, 435 yeast FRT sites, 435 Z Z line, 612, 612f, 613f Zellweger (cerebrohepatorenal) syndrome, 215, 579–580, 580t zinc absorption of, 101 human requirement for, 93, 93t multivalent states of, 93, 94f, 94t physiologic roles of, 98, 99f 2019 toxicity of, 95t zinc finger, 98 structure of, 95f zinc finger motif, 426, 426f zona pellucida, 553 zwitterions, 19 zymogens, 87, 627 protease secretion as, 521 2020 目录 Title Page Copyright Page Contents Preface SECTION I Structures & Functions of Proteins & Enzymes Biochemistry & Medicine Water & pH Amino Acids & Peptides Proteins: Determination of Primary Structure Proteins: Higher Orders of Structure SECTION II Enzymes: Kinetics, Mechanism, Regulation, & Role of Transition Metals Proteins: Myoglobin & Hemoglobin Enzymes: Mechanism of Action Enzymes: Kinetics Enzymes: Regulation of Activities 10 The Biochemical Roles of Transition Metals SECTION III Bioenergetics 17 21 21 31 53 74 98 134 134 156 188 223 247 277 11 Bioenergetics: The Role of ATP 12 Biologic Oxidation 13 The Respiratory Chain & Oxidative Phosphorylation SECTION IV Metabolism of Carbohydrates 14 Overview of Metabolism & the Provision of Metabolic Fuels 15 Carbohydrates of Physiological Significance 16 The Citric Acid Cycle: The Central Pathway of Carbohydrate, Lipid, & Amino Acid Metabolism 17 Glycolysis & the Oxidation of Pyruvate 18 Metabolism of Glycogen 19 Gluconeogenesis & the Control of Blood Glucose 2021 277 292 308 336 336 363 382 397 412 429 20 The Pentose Phosphate Pathway & Other Pathways of Hexose Metabolism SECTION V Metabolism of Lipids 21 Lipids of Physiologic Significance 22 Oxidation of Fatty Acids: Ketogenesis 23 Biosynthesis of Fatty Acids & Eicosanoids 24 Metabolism of Acylglycerols & Sphingolipids 25 Lipid Transport & Storage 26 Cholesterol Synthesis, Transport, & Excretion 452 483 483 512 535 564 581 611 SECTION VI Metabolism of Proteins & Amino Acids 643 27 Biosynthesis of the Nutritionally Nonessential Amino Acids 28 Catabolism of Proteins & of Amino Acid Nitrogen 29 Catabolism of the Carbon Skeletons of Amino Acids 30 Conversion of Amino Acids to Specialized Products 31 Porphyrins & Bile Pigments 643 661 687 726 749 SECTION VII Structure, Function, & Replication of Informational Macromolecules 32 Nucleotides 33 Metabolism of Purine & Pyrimidine Nucleotides 34 Nucleic Acid Structure & Function 35 DNA Organization, Replication, & Repair 36 RNA Synthesis, Processing, & Modification 37 Protein Synthesis & the Genetic Code 38 Regulation of Gene Expression 39 Molecular Genetics, Recombinant DNA, & Genomic Technology SECTION VIII Biochemistry of Extracellular & Intracellular Communication 40 Membranes: Structure & Function 41 The Diversity of the Endocrine System 42 Hormone Action & Signal Transduction 783 783 801 827 855 911 955 992 1051 1120 1120 1174 1224 SECTION IX Special Topics (A) 1270 43 Nutrition, Digestion, & Absorption 1270 2022 44 Micronutrients: Vitamins & Minerals 45 Free Radicals & Antioxidant Nutrients 46 Glycoproteins 47 Metabolism of Xenobiotics 48 Clinical Biochemistry SECTION X Special Topics (B) 49 Intracellular Traffic & Sorting of Proteins 50 The Extracellular Matrix 51 Muscle & the Cytoskeleton 52 Plasma Proteins & Immunoglobulins 53 Red Blood Cells 54 White Blood Cells SECTION XI Special Topics (C) 55 Hemostasis & Thrombosis 56 Cancer: An Overview 57 The Biochemistry of Aging 58 Biochemical Case Histories 1289 1324 1335 1358 1368 1403 1403 1448 1491 1529 1575 1601 1629 1629 1656 1721 1748 The Answer Bank Index 1776 1792 2023 ... and function from super-resolution fluorescence microscopy Bioessays 20 12; 34:739-747 Wiley Periodical, Inc Copyright © 20 12. ) Caveolae may derive from lipid rafts Many, if not all, contain the... by high Na+ and Ca2+ content, and Cl− is the major anion These ionic differences are maintained due to various membranes found in cells These membranes have unique lipid 1 122 and protein compositions... (see Chapter 21 ) Phosphatidylcholine is generally the major phosphoglyceride by mass in the membranes of human cells FIGURE 40 2 A phosphoglyceride showing the fatty acids (R1 and R2), glycerol,