Index...

Page numbers in bold indicate main discus-sion of topic. Page numbers followed by fdenote figures. “See” cross-references directthe reader to the synonymous term. “Seealso” cross-references direct the reader torelated topics. [Note: Positional and configura-tional designations in chemical names (forexample, “3-“, “α”, “N-“, “D-“) are ignored inalphabetizing.

AAβ, in Alzheimer’s disease, 21Abbreviations, for amino acids, 5, 5fABCA1, 236Abetalipoproteinemia, 231Absorptive state, 321. See also Fed stateAcceptable Macronutrient Distribution Ranges

(AMDR), 360, 360fACE. See Angiotensin-converting enzymeAcetaldehyde, 317Acetanilid, 153Acetate (acetic acid), 6f, 7, 182f

in cholesterol synthesis, 220titration of, 6f, 7

Acetoacetate, 195–196, 196fformation in amino acid catabolism, 261,

262, 266, 266fAcetoacetyl CoA, formation in amino acid,

262, 266Acetone, 195, 196f, 262Acetylation, 422, 422fAcetylcholinesterase

inhibition by insecticides, 62in membrane protein anchoring, 206

Acetyl CoA, 96in absorptive/fed state, 323, 323f, 324allosteric activation of, 122amino acids that form, 266carboxylation to malonyl CoA, 183–184,

184fin cholesterol synthesis, 220in citrate synthesis, 111–112, 111fconversion of building blocks to, 93, 93fcytosolic, production of, 183decarboxylation of pyruvate to, 96, 105,

106f, 109–111, 110fin diabetes mellitus, 197in fatty acid synthesis, 183–184formation of

in amino acid catabolism, 261–262,266, 266f

in fatty acid oxidation, 192, 192fin gluconeogenesis, 119, 119f, 122in glycolysis, 96in ketone body synthesis, 195–196, 196foxidation of, 93, 93fpyruvate dehydrogenase activated by,

119, 119fpyruvate dehydrogenase complex as

source of, 109, 109fin tricarboxylic acid cycle, 109–111, 109f

Acetyl CoA-ACP acetyltransferase, 184Acetyl CoA carboxylase, 183, 185f, 190

in absorptive/fed state, 324allosteric activation of, 183–184, 184fallosteric inactivation of, 183, 184fdephosphorylation of, 184in fasting, 330hormonal regulation of, 184, 184flong-term regulation of, 184phosphorylation of, 183–184short-term regulation of, 183–184, 184f

Acetyl CoA carboxylase-2 (ACC2), 191N4-Acetylcytosine, 292fN-Acetyl-D-glucosamine, 142N-Acetylgalactosamine (GalNAc), 160, 168N-Acetylglucosamindase deficiency, 164fN-Acetylglucosamine (GlcNAc), 160, 166, 168N-Acetylglucosamine-6-sulfatase deficiency,

164fN-Acetylglutamate

synthesis of, 255f, 256in urea cycle, 253, 254f

N-Acetylglutamate synthase, 256N-Acetyllactosamine, 142CMP-N-Acetylneuraminic acid, 166N-Acetylneuraminic acid (NANA), 166

in acidic glycosphingolipids, 209synthesis of, 160

Acetyl residue, in plasma-activating factor,202, 202f

Acid/base propertiesof amino acids, 6–9Henderson-Hasselbalch equation for, 6–9

Acidemiaketone bodies and, 197methylmalonic, 194

Acid hydrolases, 162Acidic amino acids, 3f, 5Acidic sugars

in glycosaminoglycans, 157, 157f, 161,162f

synthesis of, 161, 162fAcid maltase, 130Aciduria

homogentisic, 274methylmalonic, 194orotic, 303, 303f

Acne, retinoic acid for, 385Aconitase

in citrate isomerization, 111f, 112inhibition of, 112

Acquired hyperammonemia, 258ACTH, 239, 239fActive sites, 54, 54f, 56, 57Acute intermittent porphyria, 280, 281fAcyl carrier protein (ACP), 184Acyl CoA:cholesterol acyltransferase (ACAT),

177, 233f, 234, 234fAcyl CoA dehydrogenase, 76Acyl CoA derivatives, α-β-unsaturated, 266Acyl CoA:diacylglycerol acyltransferase

(DGAT), 176Acyl CoA:monoacylglycerol acyltransferase

(MGAT), 176Acyl CoA oxidase, 195Acyltransferases, 176–177Added sugars, 365Adenine, 291, 291f, 292f, 305f, 396, 396f, 397

in codons/genetic code, 431, 432f

pairing with thymine, 396f, 397, 398fAdenine arabinoside (vidarabine, araA), 409Adenine phosphoribosyltransferase (APRT),

296, 296fAdenosine deaminase (ADA), 299

deficiency of, 298, 300f, 301–302gene therapy for, 485, 486f

Adenosine diphosphate (ADP)in ATP synthesis, 73, 77–78, 78fisocitrate dehydrogenase activation by,

112transport of, to inner mitochondrial

membrane, 79in tricarboxylic acid cycle regulation, 114,

114fin urea cycle, 255–256ribosylation, 95

Adenosine monophosphate (AMP; also calledadenylate)

cyclic. See Cyclic adenosinemonophosphate (cAMP)

gluconeogenesis and, 123glycogen degradation, 132, 133fIMP conversion to, 295–296, 295fphosphofructokinase-1 activated by, 99in urea cycle, 255–256

Adenosine triphosphate (ATP)in aerobic glycolysis, 97–98, 100f,

102–104in amino acid deamination, 252in amino acid transport, 249in anabolic pathways, 93in anaerobic glycolysis, 104in catabolic pathways, 91, 93fchange in free energy of, 77in cholesterol synthesis, 220as energy carrier, 72–73, 73fin fatty acid synthesis, 183, 183fin glycolysis, 96in GMP synthesis, 295–296hydrolysis of, standard free energy of, 73isocitrate dehydrogenase inhibition by,

112in muscle contraction, 132as phosphate donor, 63, 73phosphofructokinase-1 inhibited by, 99production/synthesis of

in fatty acid oxidation, 192, 192fin inner mitochondrial membrane, 74in oxidative phosphorylation, 73, 73f,

77–80by 3-phosphoglycerate, 101–102in pyruvate formation, 102–103in tricarboxylic acid cycle, 109, 113,

113f, 114fin protein degradation, 247in protein synthesis, 437structure of, 73, 73ftransport to inner mitochondrial

membrane, 79in urea cycle, 255–256

Adenylate kinase, 296, 296fAdenylyl (adenylate) cyclase, 134, 151

Bordetella pertussis and, 95glucagon and, 314lactose operon and, 451f, 452in metabolic regulation, 94–96, 95fin triacylglycerol degradation, 190Vibrio cholerae and, 94

Adequate Intake (AI), 358, 359fAdipocytes

free fatty acids reesterified in, 178

489

Index

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Index490

in obesity, 350–351volume of, 324f, 325

Adiponectinin diabetes mellitus, 343in obesity, 353

Adipose tissuein absorptive/fed state, 324–325

carbohydrate metabolism in, 325, 325ffat metabolism in, 325, 325fintertissue relationships of, 328f

communication with other metabolicorgans, 307, 307f

in diabetes mellitustype 1, 339, 339ftype 2, 343, 344

in energy metabolism, 307, 307fas energy storage depot, 324–325in fasting, 327, 330f, 331, 331f

carbohydrate metabolism in, 331, 331ffat metabolism in, 331, 331fintertissue relationships of, 328f

fatty acids in, as fuel reserve, 189hormones of, and obesity, 352–353hyperplasia of, 351hypertrophy of, 351insulin resistance and, 343lipoprotein lipase in, 228–229metabolic role of, 307in obesity, 324–325subcutaneous, 350triacylglycerol fate in, 189visceral, 350

A-DNA, 398ADP. See Adenosine diphosphateAdrenal cortex, cholesterol synthesis in, 220Adrenal cortical steroid hormones

deficiency of, 238fsecretion of, 239, 239f

Adrenal medulla, tyrosine hydroxylase in, 286Adrenergic symptoms, of hyperglycemia, 315Adrenocorticotropic hormone (ACTH), 239,

239fAdrenoleukodystrophy, 195, 236Afferent signals, 352–353, 353fAfrican Americans

lactose intolerance in, 88sickle cell disease in, 35

Age-related macular degeneration (AMD),459–460

Aggrecan, 158Aging, telomeres and, 408Alanine, 253

amino group ofdissociation of, 7f, 8primary, 4f

in ammonia transport, 253, 253fcarboxyl group of, dissociation of, 7, 7fcatabolism of, 263, 263fdipolar form of, 7, 7fisoelectric form of, 7f, 8–9optical properties of, 5, 5fpeptide bond with valine, 13, 14fpKs of, 8side chains of, 2fsynthesis of, 267–268, 268ftitration of, 7–9, 7f, 8ftransamination of, 263, 263f

β-Alanine, 304Alanine aminotransferase (ALT), 250, 250f,

251, 251fdiagnostic value of, 251–253in jaundice, 284in liver disease, 251–252, 251fmechanism of action, 251

ALA synthase, 278effects of drugs on, 279in porphyrias, 280

Albinism, 263, 268f, 269f, 273, 273f, 288oculocutaneous, 272, 272f

Albuminof aldosterone, 237of bile acid, 225of bilirubin, 282of free fatty acids, 178, 190function of, 4

Alcoholcoronary heart disease and, 364–365in cirrhosis of liver, 318in fatty liver, 318in glycerophospholipids, 202hypoglycemia and, 317–318, 317fmetabolism of, 317–318, 317fWernicke-Korsakoff syndrome and, 379

Alcohol dehydrogenase, 317Aldehyde dehydrogenase, 317Aldolase, 100Aldolase A, 138, 138fAldolase B, 138, 138f

deficiency of, 138Aldose reductase, 139, 140, 141f, 142Aldoses, 83, 83fAldosterone, 237, 237f, 239, 240fAlkaline phosphatase, 206Alkaptonuria, 263, 268f, 269f, 274, 274fAlkyl group

saturated, in plasma-activating factor,202, 202f

unsaturated, in plasmalogens, 202, 202fAllantoin, 298Allele-specific oligonucleotide (ASO) probe,

472, 472f, 485fAllolactose, 451fAllopurinol, 301Allosteric activators

in absorptive/fed state, 321, 321fin fasting, 328in metabolic regulation, 94

Allosteric effectors, 27, 41f, 62–63, 62fin absorptive/fed state, 321, 321fcarboxylation of pyruvate and, 119in fasting, 328glucagon levels and, 122

Allosteric enzymes, 57, 67fin committed (rate-limiting) step of

pathway, 62effectors or modifiers of, 62–63, 62f, 64f

heterotropic, 63homotropic, 62–63negative, 62positive, 62

sigmoidal kinetics curve of, 57, 62f, 63Allosteric inhibitors, in metabolic regulation,

94, 252Allysine, in collagen biosynthesis, 48, 48fα-Amanita, RNA polymerase II inhibition by,

424α1-Antitrypsin (α1-AT)

deficiency of, 51fin emphysema, 50

in elastin degradation, 50, 50fin lungs, 50, 50f

α cells, 313α chains, in collagen, 43–44, 43f

precursors of (pro-α-chains), 45, 46fα-helix, 16–17, 16f

amino acids disrupting, 16–17amino acids per turn, 16in myoglobin, 26, 26f

Alpha-Tocopherol, Beta Carotene Cancer

Prevention Trial, 391Alternative splicing, 457, 457fAlzheimer disease, 21, 21f, 23f, 231Amanita phalloides, 251f, 424Amidation, synthesis of nonessential amino

acids by, 268Amide group, in amino acid side chains, 4Amine oxidase, 257Amine(s)

ammonia from, 257biologically active, 285–287

Amino acid analyzer, 15, 15fD-Amino acid oxidase, 253Amino acid pool, 246, 246fAmino acid(s), 1–12

abbreviations and symbols for, 5, 5fabsorption of, 249in absorptive/fed state, 321acid/base properties of, 6–9acidic, 3f, 5in α-helix, 16–17amino group of, 1, 1f, 4f, 7f, 8ammonia from, 256amphoteric properties of, 9attachment to tRNA

enzymes required for, 435, 435fsite for, 434f, 435

basic, 3f, 5branched-chain, 326

catabolism of, 266–267, 266fdehydrogenation of, 266–267oxidative decarboxylation of, 266transamination of, 266

as buffers, 6–7, 6f, 8, 9, 9fcarbon skeletons of, 245, 250

catabolism of, 262–267carboxyl group of, 1, 1f, 4f, 7catabolism/degradation of, 245, 249–253,

261–267, 261fin absorptive/fed state, 323f, 324acetoacetyl CoA formation in, 266acetyl CoA formation in, 266, 266ffumarate formation in, 263, 263fα-ketoglutarate formation in, 250–252,

250f, 252f, 262, 263foxaloacetate formation in, 262, 262fpyruvate formation in, 263, 263fsuccinyl CoA formation in, 263–265,

264fclassification of, 2–3f, 2–5, 261, 262fclinically important, 275fconcept map, 11fconversion to specialized products,

277–290, 277fD and L forms of, 5, 5fde novo synthesis of, 245dietary, 245disulfide bonding by, 4essential, 261, 262f, 367, 434free, 1, 1fglucagon secretion and, 313, 313fglucogenic, 261, 262f, 266in gluconeogenesis, 118hydrogen bonding by, 4, 4fhydrophobic interactions of, 4, 19, 19fin insulin secretion, 310ionic interactions of, 19, 19fketogenic, 262, 262f, 266metabolism of, 261f

in absorptive/fed state, 323f, 324, 326,326f

concept map, 275ffolic acid in, 267metabolic defects in, 270–274

net charge, at neutral pH, 8


Index 491

nitrogen removal from, 245, 250–253in urea cycle, 245f, 253–256, 253f,

254f, 255fnonessential, 261, 262f

biosynthesis of, 267–269, 268fnonpolar, 2–4, 2f, 4f

location in proteins, 2, 4, 4foptical properties of, 5, 5foxidative deamination of, 252–253, 252f

allosteric regulation of, 252coenzymes in, 252, 252fdirection of reactions, 252

peptide bonds of, 1, 1f, 13–14, 14fas precursors of nitrogen-containing

precursors, 277, 277fin protein synthesis, 434as proton acceptors, 5as proton donors, 5residue or moiety, 14sequence of, 14–16

in collagen, 45, 45fdetermination of, 14–15, 15fDNA analysis of, 15–16

side chains of, 1–5, 1f, 2–3fas attachment site for other

compounds, 4structure of, 1–5, 1fsubstitution of

in hemoglobin C disease, 36f, 37in sickle cell disease, 36, 36f

titration of, 6f, 7–9, 8f, 9ftransamination of, 245, 250–252, 250f,

251fequilibrium of reactions, 251

transport into cells, 249–250uncharged polar, 3f, 4

Amino acid starvation, stringent responseand, 454, 454f

Aminoacyl-tRNA synthetase, 435, 435f, 437Amino group, 1, 1f, 11f

α, transfer of (transamination), 245,250–252, 250f, 251f, 266

dissociation of, 7f, 8peptide bind to carboxyl group, 13–14, 14fprimary, 4, 4fremoval of (deamination), 245, 252–253,

252f, 261secondary, 4, 4f

β-Aminoisobutyrate, 304δ-Aminolevulinic acid (ALA), formation of,

278–279, 278fδ-Aminolevulinic acid dehydrase, 278f, 279δ-aminolevulinic acid synthase-2 (ALAS-2),

278Aminopeptides, 249Amino sugars


synthesis of, 160, 161fAminotransferase(s), 250, 250f

action mechanism of, 251diagnostic value of, 251–253, 251fin liver disease, 251–252, 251fin non-hepatic disease, 252substrate specificity of, 250–251

Ammoniafrom amines, 257from amino acids, 256from bacterial action in intestines, 257disposal as urea, 253, 257, 257felevated levels of, 257–258, 258ffrom glutamine, 256–257, 257fin fasting, 332in liver disease, 258metabolism of, 245, 256–258, 257f

as product of amino acid catabolism,250, 253, 253f

from purines and pyrimidines, 257sources of, 256–257transport through circulation, 257, 257ftransport to liver, 253, 253f

Ammonia intoxication, 257Amniotic fluid, as DNA source, 476, 477fAmoxicillin, 62AMP. See Adenosine monophosphateAMP-activated protein kinase (AMPK), 223

in acetyl CoA carboxylase regulation,184, 184f

in fasting, 330Ampholytes, 9Amphoteric properties, of amino acids, 9α-Amylase, 86, 87fAmylo-α(1→4) → α(1→6)-

transglucosidase, 128Amylo-α-(1→6)-glucosidase, 130Amyloid beta, 21

in Alzheimer’s disease, 21Amyloid plaques, 21, 21fAmyloid precursor protein, 21Amyloid protein, 21Amylose, 128Amytal, 76fAnabolic pathways, 91, 93

catabolic pathways vs., 93, 93fas divergent process, 93

Anabolism, insulin and, 308Anaerobic glycolysis, 96, 96f, 102–104,

104fenergy yield from, 104, 104f

Analgesics, for sickle cell disease, 36Anaplerotic reactions, 109Androgens, 237

secretion of, 239Android or apple-shaped, 350, 350fAndrostenedione, 239Anemia(s)

2,3-bisphosphoglycerate in, 32folic acid deficiency and, 374–375,

374f, 375fhemolytic

glycolytic enzyme deficiencies and,102–103

in G6PD deficiency, 153iron-deficiency, 374, 374fAmacrocytic, 374, 374fmegaloblastic, 267, 374, 375, 393fmicrocytic, 374, 374fnormocytic, 374fnutritional, 374, 374fpernicious, 377, 393fsickle cell. See Sickle cell diseasevitamin B12 deficiency and, 374, 374f,

375fAnencephaly, 375Angiotensin-converting enzyme (ACE), 239Angiotensin-converting enzyme (ACE)

inhibitors, 62Angiotensin I, 239Angiotensin II, 62, 239Animal protein, 367, 367fAnion-exchange column, 14Anomeric carbon, 84Anoxia, caused by sickle cell disease, 36,

37fAntibiotic resistance, plasmids and, 467,

467f, 468fAntibiotics

G6PD deficiency and, 153for sickle cell disease, 36

targeting DNA gyrase, 401targeting RNA synthesis, 421, 422f

Antibodies, labeled, 472Anticancer drugs

blocking DNA replication, 409, 409fDNA gyrase as target of, 401as inhibitors of deoxyribonucleotide

synthesis, 298as inhibitors of purine synthesis, 293,

294f, 295as inhibitors of thymidylate synthase,

303–304intercalating into DNA double helix, 397

Anticodon, 435antiparallel binding with codon, 437, 437f

Antimalarial drugs, 153Antimycin A, 76fAntioxidant reactions, enzymes catalyzing,

148, 148fAntioxidant(s), 148–149, 377–378, 391Antiparallel binding, 434f, 437, 437fAntiparallel β sheet, 17, 17fAntipyretics, 153AP-endonuclease, 412apo B, 457f, 458apo B-48 protein, 457f, 458Apoenzyme, 54Apoferritin, 459Apolipoprotein B-48, 177, 228Apolipoprotein B-100, 189, 231Apolipoprotein C-II, 231Apolipoprotein E, 231, 234Apolipoprotein(s)

classes of, 227HDL as reservoir of, 234synthesis of, 228

Apoproteins. See Apolipoprotein(s)Apoptosis, mitochondria and, 80Appetite, 352–353AraA, 409Arabinose, 409AraC, 409Arachidonic acid, 182, 182f, 183f, 363

in prostaglandin synthesis, 213, 214, 215fArginase, 262Arginine, 5, 262

α-helix disrupted by, 16–17catabolism of, 262cleavage to ornithine and urea, 255in creatine synthesis, 287, 288fin histones, 410as nitric oxide synthase substrate, 151,

151fside chains of, 3ftransport of, 250in urea cycle, 253–255, 254f

Argininosuccinatecleavage of, 255synthesis of, 255in urea cycle, 253–255, 254f

Argininosuccinate lyase, 254fArgininosuccinate synthase, 254fArgonaute (Ago), 459Aromatase (CYP19), 239Arsenic poisoning, 101

mechanism of, 111Arsenite, 111Arthritis

alkaptonuria and, 274chronic gouty, 299

Arthrocentesis, 301Ascorbate, 148Ascorbic acid, 377–378, 392f. See also

Vitamin C


Index492

deficiency of, 47Ashkenazi Jews, phospholipid disorders in,

208, 211Asians, lactose intolerance in, 88A sites, on ribosome, 436Asparaginase, 262Asparagine

metabolism of, 262, 262fside chains of, 3f, 4synthesis of, 268

Asparagine synthetase, 268Aspartate transcarbamoylase, 302Aspartame, 272Aspartate aminotransferase (AST), 250–253,

250f, 251f, 256diagnostic value of, 251–253in jaundice, 284

Aspartate (aspartic acid), 5, 19fα-helix disrupted by, 16–17as atom source for purine ring, 292, 293fas atom source for pyrimidine ring, 302,

302fmetabolism of, 262, 262foxaloacetate production and, 113as product of amino acid catabolism, 251as proton donor, 5side chains of, 3f, 5

carboxylate group of, 5synthesis of, 267–268, 268fin urea cycle, 253–255, 254f

Aspirinantithrombotic effect of, 214, 216fas uncoupler, 79

AST. See Aspartate aminotransferaseAsthma, 214Atherosclerosis, 219, 227

diabetes mellitus and, 345homocysteine and, 263pathogenesis of, 234, 235fpremature, 232

Atherosclerotic plaque, 234, 235fAtorvastatin, 61, 61f, 224ATP. See Adenosine triphosphateATP-ADP transport, 79ATPase, 232ATP-binding cassette (ABC) protein, 236ATP-citrate lyase, 183, 186ATP-dependent RNA-DNA helicase, 421ATP synthase, 78–79ATP synthase complexes, 74Atractyloside, 79Autoglucosylation, 127Autoimmune attack, in type 1 diabetes

mellitus, 338, 338fAutophosphorylation, 312Avidin, 381, 472Axis of symmetry, 397, 397fAZT (zidovudine), 409, 409f

Bβ-α-β unit, 18fBackward reactions, free energy change in,

70Bacterial artificial chromosomes (BACs), 468Bacterial operons, transcription from,

450–452, 451fwhen glucose is only sugar available, 452when lactose is available, 452

Bacteriophage lambda, 468Barbiturates, porphyria and, 280Base exchange reaction, in

phosphatidylserine synthesis, 204f,205

Base excision repair, 412, 413fBasement membranes, collagen in, 44Base pairing, 396f, 397, 397fBasic amino acids, 3f, 5β-barrel protein motif, 18fB-DNA, 398, 399f, 460Behavioral factors, in obesity, 352Benzoyl peroxide, 385Beriberi, 379, 393fβ-bends, 17β-carotene

as antioxidant, 149, 377, 382for porphyria, 282

β cells, 307, 308fdestruction, in type 1 diabetes mellitus, 338dysfunction, in type 2 diabetes mellitus,

341, 343–344glucose phosphorylation in, 98insulin secretion by, 307–309, 309f, 310f

β-oxidation, 190–195β-sheets, 17, 17fBH4, 270–271Bicarbonate buffer system, 9, 9fBidirectional replication, of DNA, 399, 400fBile, bilirubin excretion in, 283, 283fBile acid(s), 224–227

amphipathic nature of, 224cholesterol as precursor of, 219, 224conjugated, 225as emulsifying agents, 224enterohepatic circulation of, 225–226, 226fprimary, 224structure of, 224, 224fsynthesis of, 224, 225f

Bile acid sequestrants, 225Bile duct obstruction, jaundice and, 284Bile pigments, 282. See also BilirubinBile salts, 175, 224–227

cholesterol as precursor of, 225deficiency of, 226–227, 226fenhanced amphipathic nature of, 225in enterohepatic circulation, 225–226, 226fintestinal flora action on, 225secondary, 225structure of, 175, 175fsynthesis of, 225, 225f

Bilirubinas antioxidant, 282concentration of, determination of, 285conjugated, 282–283, 283f, 285direct-reacting, 285drugs displacing, 282elevated levels, in jaundice, 284–285, 284f,

285fformation of, 282, 282findirect-reacting, 285metabolism of, 282, 283fsecretion into bile, 283, 283ftransport of, 282unconjugated, 283, 285uptake by liver, 282, 283f

Bilirubin diglucuronide, formation of, 282–284,282f, 283f

Bilirubin glucuronyltransferase, 282in neonatal jaundice, 285, 285f

Biliverdin, 282Biochemical pathways, 54fBiocytin, 118Bioenergetics, 69–82. See also Free energyBiotechnology, 465–488

analysis of gene expression, 483–485,484f, 485f

DNA cloning, 467–470, 467f, 468f, 469f,

470fgene therapy, 485, 486fpolymerase chain reaction, 479–483, 481f,

482f, 483fprobes, 470–472, 471f, 472f, 473frestriction endonucleases, 465–466, 465f,

466f, 467frestriction fragment length polymorphism,

473–479, 475f, 476f, 477f, 478f,479f, 480f

Southern blotting, 473, 474ftransgenic animals, 486

Biotin, 265, 381, 381f, 392–393fas coenzyme, 381

in carbonic acid transport, 267in carboxylation of acetyl CoA, 183in carboxylation of propionyl CoA, 194,

195fin carboxylation of pyruvate, 105, 118

deficiency of, 381Dietary Reference Intakes for, 358fin DNA probes, 472structure of, 381, 381f

Biotin-linked enzyme, 444, 444fBiotinylated probes, 4721,3-Bisphosphoglycerate, synthesis of, 1012,3-Bisphosphoglycerate

in anemia, 32binding of fetal hemoglobin to, 33binding site of, 31, 31fbinding to deoxyhemoglobin, 31, 31fin hypoxia, 32, 32foxygen affinity of hemoglobin and, 29,

31–32, 32fsickle cell disease and, 36stripped of hemoglobin, 32synthesis of, 31, 31f

in red blood cells, 101in transfused blood, 32

Bisphosphoglycerate mutase, 101Blindness, vitamin A and, 384–385, 385fBlood-brain barrier, 327Blood clots, prostaglandins and, 214Blood coagulation, vitamin K and, 389, 390fBlood transfusions

2,3-bisphosphoglycerate in, 32for β-thalassemia, 39hemosiderosis and, 39for sickle cell disease, 36

Blunt ends, of DNA fragment, 466, 466fβ-meander, 18fBody fat, deposition of

anatomical differences in, 350, 350fbiochemical differences in, 350

Body mass index (BMI), 349, 349f, 353f, 354fBody weight. See also Obesity

effects of over- and underfeeding on, 351,351f

reduction in, 354–355regulation of, 351–352set point for, 351settling point for, 351

Bohr effect, 30–31mechanism of, 31source of protons that lower pH, 30, 30f

Bone marrowheme synthesis in, 278histology in normal and folate-deficient

individuals, 375fBone(s)

collagen in, 43vitamin D and, 388

Bordetella pertussis, 95

168397_P489-520.qxd7.0:34 Index 6-2-04 26p 2010.4.5 10:03 AM 92

Index 493

Boron, Dietary Reference Intakes for, 358fBovine spongiform encephalopathy, 22Bowel, shortened, steatorrhea with, 177Brain

in absorptive/fed state, 326–327, 327fcarbohydrate metabolism in, 327, 327ffat metabolism in, 327, 327fintertissue relationships of, 328f


in energy metabolism, 307, 307fin fasting, 332, 332fglucose requirements for, 327, 332ketone bodies utilized by, 196, 327, 332,

332fmetabolic priority for, 326metabolic role of, 307oxygen consumption of, 327

Branched-chain α-amino acidaminotransferase, 266

Branched-chain α-ketoacid dehydrogenase,111, 272–273

deficiency in, 266Branched-chain α-keto acid dehydrogenase

complex, 266Branched-chain amino acid(s)

absorption of, 249in absorptive/fed state, 326catabolism of, 266–267, 266fdegradation of, limited hepatic ability for,

324dehydrogenation of, 266oxidative decarboxylation of, 266transamination of, 266

Branched-chain fatty acid(s), 195, 195fBranching enzyme, 128Branch site, 427Brittle bone syndrome. See Osteogenesis

imperfectaBroad beta disease, 231Brown fat (adipocytes), 79Brush border membrane

carbohydrate digestion in, 86lipid absorption in, 176

Buffer pairs, 8Buffers, 6–7Butyric acid, 182fButyryl, 186

CCAAT box, 423, 423fCAG codon, 433, 433fCalcitonin, 387fCalcium

as activatorof glycogen degradation, 131–132,

132fof isocitrate dehydrogenase, 112of PDH phosphatase, 111

Dietary Reference Intakes for, 358finsulin release and, 310muscle action and, 131–132, 132fin nitric oxide synthesis, 151regulation by calmodulin, 132, 132fvitamin D and, 386, 388, 388f

Calcidiol vitamin D, 386Calcitriol vitamin D, 386Calcium/phosphatidylinositol system, 94Calmodulin

calcium action and, 132, 132fCaloric consumption, 365, 365fCaloric restriction, weight reduction and, 354Calorimeter, 359cAMP. See Cyclic adenosine monophosphate

cAMP-dependent protein kinaseglucagon and, 122, 314in glycogen degradation, 132in pyruvate kinase regulation, 102

cAMP-dependent protein kinase A, 134cAMP-directed pathway

activation of glycogen degradation by,132–133, 133f

inhibition of glycogen synthesis by,133–134, 134f

cAMP phosphodiesterase, 95cAMP regulatory protein (CRP), 452cAMP response element binding protein

(CREB), 457cAMP response element (CRE), 457Cancer. See also Anti-cancer drugs

diet and, 361fDNA repair defects and, 413obesity and, 354telomeres and, 408ultraviolet radiation and, 412

5’ capping, in mRNA, 425–426, 426f, 457Capric acid, 182fCaptopril, 62Carbamate, 32Carbamino-hemoglobin, 32Carbamoyl phosphate, synthesis of, 253–255,

254f, 302Carbamoyl phosphate synthetase I (CPS I),

253–255, 255fCPS II vs., 302, 302fdeficiency of, 258f

Carbamoyl phosphate synthetase II (CPS II),255

CPS I vs., 302, 302fCarbohydrate(s), 83–90

with aldehyde group (aldoses), 83, 83fclassification of, 83–86complex, 85–86dietary, 357, 357f, 365–367

acceptable distribution ranges for, 360,360f

blood glucose and, 366, 366fclassification of, 365–366energy content of, 359, 359fprotein-sparing effect of, 369requirements for, 367

digestion of, 86–88by enzymes synthesized by intestinal

mucosal cells, 86–87, 87fin mouth, 86, 87fby pancreatic enzymes, 86, 87fin small intestine, 86, 87f

enantiomers, 84, 85fepimers, 83–84, 84fwith free carbonyl group, 83functions of, 83in glycoproteins, 165–166glycosidic bonds between, 83, 84fglycosidic bonds to non-carbohydrate

structure, 84–85, 85fin glycosphingolipids, 208isomers, 83–84, 84fwith keto group (ketoses), 83, 83fmetabolism of

in absorptive/fed stateadipose tissue, 325, 325fcerebral, 327, 327fhepatic, 322–324, 323fskeletal muscle, 326, 326f

in fasting, 329–330, 330f, 331, 331f,332f

glucagon and, 314insulin and, 310, 311

simple, empiric formula for, 83as structural component, 83structure of, 83–86

Carbon dioxideaddition of. See Carboxylationas atom source for purine ring, 292,

293fas atom source for pyrimidine ring, 302,

302fbinding of, and oxygen affinity of

hemoglobin, 32concentration of, and oxygen affinity of

hemoglobin, 30partial pressure of. See PCO2in pentose phosphate pathway,

145–146production of, in citric acid cycle, 114fremoval of. See Decarboxylation

Carbonic acid, 267Carbonic anhydrase, 30Carbon monoxide binding, oxygen affinity

of hemoglobin, 32–33, 32f, 41fCarbon monoxide poisoning, 33Carbon monoxyhemoglobin (HbCO), 32Carbon skeletons

catabolism of, 262–267Carbon skeletons, of amino acids, 245,

249Carbonyl groups, 4fγ-Carboxyglutamate, 389, 389fCarboxyhemoglobin, 32β-Carboxyl, 268γ-Carboxyl, 268Carboxylate group, 5Carboxylation

of acetyl CoA, 183–184, 184fof glutamate, 389, 389fof proteins, 444, 444fof pyruvate, 105, 106f, 118–119, 119f

Carboxyl group, 1, 1f, 11faddition to proteins, 443, 444fdissociation of, 7, 7fpeptide bond to amino group, 13, 14f

Cardiac musclecarnitine deficiency in, 192lipoprotein lipase in, 228myoglobin in, 26skeletal vs., 326

Cardiac troponin I (cTnl), 66Cardiolipin, 202, 202f

synthesis of, 206Cardiovascular disease, homocysteine in,

263, 265Carnitine

deficiencies of, 192congenital, 192secondary, 192

in fatty acid oxidation, 190–192, 191ffunctions of, 190–191sources of, 191

Carnitine-acylcarnitine translocase, 191Carnitine acyltransferase I (CAT-I). See

Carnitine palmitoyltransferase ICarnitine palmitoyltransferase I (CPT-I),

191deficiency in, 192

Carnitine palmitoyltransferase II (CPT-II),191, 192

deficiency in, 192Carnitine shuttle, 190–191, 191fCartilage pigmentation, in alkaptonuria,

274Caspases, 80Catabolic pathways, 91–93, 93f


Index494

anabolic pathways vs., 93, 93fas convergent process, 93conversion of building blocks to simple

intermediates in, 93, 93fhydrolysis of complex molecules in, 93,

93foxidation of acetyl CoA in, 93, 93fstages of, 91–93, 93

Catabolism. See also specific pathwaysof amino acids, 245, 249–253, 261–267,

261fof branched-chain amino acids, 266–267,

266fCatabolite gene activator protein (CAP), 452Catalase, 25, 150, 195, 277Cataracts, 141, 345Catecholamine(s), 285–287

degradation of, 286, 286ffunction of, 285monoamine oxidase inhibitors, 286–287,

286fsynthesis of, 270f, 285–286, 286f

Catechol-O-methyltransferase (COMT), 286,286f

Cation-exchange chromatography, 14–15,15f

-CCA sequence, 425, 425fCDP, in phospholipid synthesis, 203, 203fCDP-choline, 203, 203fCDP-ethanolamine, 203, 203fcDNA, 469Cefamandole, 390Cefoperazone, 390Celecoxib, 214Celiac disease (celiac sprue), 249Cell cycle, eukaryotic, 406–407, 407fCell membrane, phospholipids in, 201Cell(s)

communication between, 94, 94fsenescence in, telomerase and, 408, 408fsignals within, 94

Cell surface antigenicity, 165, 165fCell-surface receptors, 456–457, 456fCell surface recognition, 165, 165fCellulose, 84Central dogma of molecular biology, 395,

395fCentral nervous system. See also Brain

tyrosine hydroxylase in, 286Cephalosporins, 390Ceramidase, 208Ceramide(s), 203f, 206, 208Cerebrocan, 158Cerebrosides, 209Chaperones, 20, 23fChargaff Rule, 397Chemical signaling, metabolic regulation via,

94–96, 95fchemiosmotic hypothesis, 77–79Chenodeoxycholic acid, 224, 224f, 225fChief cells, 248Chirality, in amino acids, 5, 5fChloramphenicol, 153, 440fChocolate cyanosis, 38Cholecalciferol (vitamin D3), 386, 386fCholecystokinin (CCK), 176, 248

obesity and, 310, 353Cholelithiasis, 226–227, 226fCholestanol, 224Cholesterol, 219–224

absorption by intestinal mucosal cells,176

bile salts and excretion of, 225concept map, 243fconversion to pregnenolone, 238, 238f

coronary heart disease and, 360–361,361f, 364–365, 364f

degradation of, 224de novo synthesis of, 219deposition of (plaques), 219dietary, 219, 364, 364fendocytosis of, 232, 233f

effect on cellular homeostasis, 232–234esterification of, 234–235excretion of, 224functions of, 219hepatic regulation of, 219, 219fas hydrophobic compound, 219in lipoproteins, 219, 227, 228f, 232f

high density, 232flow density, 231–234, 232fvery low density, 232f

metabolism of, 219–224in obesity, 353plasma, 220, 360–361, 361f

coronary heart disease and, 360–361,361f

in plasma lipoproteins, 219, 227, 227fas precursor of bile acids, 219as precursor of vitamin D, 219reverse transport of, 235–236, 236fin steroid hormone synthesis, 237–238structure of, 219–220, 220f, 237fsynthesis of, 220–224, 220f, 221f, 222f

rate-limiting step of, 220–221, 221fregulation of, 223

therapy lowering levels of, 61, 61f, 220,224, 224f, 361, 380

unesterified, HDL uptake of, 234, 236fCholesterol-7-α-hydroxylase, 224, 225fCholesterol ester hydrolase (cholesterol

esterase), 175Cholesterol ester transfer protein (CETP), 235Cholesterol gallstones, 226, 226fCholesterol side chain cleavage enzyme

complex (desmolase), 237Cholesteryl ester(s), 220, 220f

degradation of, 175fatty acids as component of, 181in lipoproteins, 227, 228f, 231, 231fresynthesis of, 176–177secretion from enterocytes, 177, 177fsynthesis of, 234, 234ftransfer from HDL to VLDL, 231, 231f

Cholestyramine, 225Cholic acid, 224, 224f, 225fCholine

Dietary Reference Intakes for, 258fas essential dietary nutrient, 204reutilization of, significance of, 204synthesis of phosphatidylcholine and,

203–204Chondrodystrophies, 162Chondroitin, 163Chondroitin sulfates, 158, 159f

degradation of, 163synthesis of, 162, 163f

Chorionic villi sampling, 476, 477fChromatin, 422, 460

condensed (heterochromatin), 422, 460gene expression, 422relaxed (euchromatin), 422remodeling, 422, 423, 460structure of, 422

Chronic granulomatous disease (CGD), 150Chromium, Dietary Reference Intakes for, 358fChromosome(s)

tracing from parent to offspring, 475–476Chronic myelogenous leukemia (CML), 298

Chronic obstructive pulmonary disease, 361fChyle, 178Chylomicron remnants

endocytosis of, 230–231fate of, 178formation of, 230–231

Chylomicron(s), 177f, 178, 227assembly of, 228composition of, 232fin diabetes mellitus type 1, 339–340, 339fin diabetes mellitus type 2, 344metabolism of, 228–231, 229fmodification of nascent, 228size and density of, 227, 227f

Chyme, 178Chymotrypsin, 56, 249fCiprofloxacin, 401Cirrhosis

ammonia levels in, 258α1-antitrypsin deficiency and, 50, 51fjaundice in, 284alcoholic, 318

Cis-acting DNA sequences, 449–450, 450fCis-acting regulatory elements, 455–456Cis fatty acids, 363fCitrate

in fatty acid synthesis, 183isomerization of, 111f, 112phosphofructokinase inhibition by, 99, 112synthesis of, from acetyl CoA and

oxaloacetate, 111–112, 111ftranslocation from mitochondrion to

cytosol, 183Citrate synthase, 111, 114, 114fCitric acid cycle. See Tricarboxylic acid (TCA)

cycleCitrulline, 257

in nitric oxide synthesis, 151, 151fin urea cycle, 255

CK. See Creatine kinaseCK2 (MB) isoenzyme, 66Clathrin, in endocytosis, 232, 233fClindamycin, 441fCloning, 465, 465fCloning, DNA, 465, 465f, 467–470, 468f

libraries of, 469–470sequencing of fragments in, 470, 471fvectors, 467–468, 470f

expression, 470, 470fplasmid, 467

CMP-NANA synthetase, 160Co-activators, 423Coagulation, vitamin K and, 389, 390fCobalamin, 264, 375–377. See also Vitamin

B12Codons, 431–432, 432f

antiparallel binding with anticodon, 437,437f

initiation, 438f, 439mutations of, 432f, 433–434, 433f, 434frecognition by tRNA, 437, 437ftermination (stop or nonsense), 432, 432ftranslation of, 431, 432f

Coenzyme A, 110, 112, 381, 381fCoenzyme Q (CoQ), 75–76Coenzyme(s), 54. See also specific enzymes

niacin as, 380in pyruvate dehydrogenase complex, 110of vitamin B12, 375–376, 376fVitamin C as, 377

Cofactors, 54Colchicine, 301Colipase, 175Collagen, 43–49


Index 495

α chains of, 43–44, 43fprecursors of (pro-α-chains), 45, 46f

amino acid sequence in, 45, 45fassembly of, 47biosynthesis of, 45–48, 46–47f, 51fconcept map, 51fcross-linking of, 45, 48, 48fdegradation of, 48diseases, 48–49, 48f, 49f, 51fextracellular cleavage of procollagen

molecules, 47fibril-associated, 44fibril formation in, 47f, 48fibril-forming, 44function of, 43glycosylation in, 45, 46f, 47hydroxylation in, 45, 45f, 46f, 47hydroxylysine in, 45, 45f, 46f, 47hydroxyproline in, 45, 45f, 46f, 47mechanical properties of, 43network-forming, 44, 45fpolypeptide precursors of, 45–47posttranslational modification of, 45secretion of, 47signal sequence for, 45structural roles of, 43structure of, 43, 43f, 45, 51ftriple helix of, 43f, 45, 46ftype I, 43–44, 44ftype II, 43–44, 44ftype III, 44, 44f

mutations, and Ehlers-Danlossyndrome, 48

type IV, 44, 44ftype IX, 44 44ftypes of, 43–44, 44ftype VII, 44, 44ftype XII, 44, 44fvitamin C and, 47, 47f

Collagenases, 48Colon cancer,Colon cancer, hereditary nonpolyposis, 411Colorimetric test, 85Combinatorial control, of transcription, 455,

455fCommon intermediate, for coupling reactions,

73Compartmentalization, of enzymes, 55Compartment for Uncoupling of Receptor and

Ligand (CURL), 232Competitive inhibition, of enzymes, 60–61, 60f

Lineweaver-Burke plot, 60, 60f, 61, 61fby statins, 61, 61f

Complementary bases, 397, 397f, 398fComplementary DNA (cDNA), 484Complementary DNA (cDNA) libraries,

469–470, 469fComplex oligosaccharides, 166, 166fCompound heterozygote, 38Concept map(s), 10

for amino acids, 11fmetabolism of, 275f

for cholesterol, 243ffor diabetes mellitus, 347ffor dietary lipid metabolism, 180ffor DNA structure, replication, and repair,

414–415ffor energy metabolism, integration of, 319ffor enzymes, 67ffatty acid metabolism, for 199ffor feed/fast cycle, 335ffor fructose metabolism, 143ffor galactose metabolism, 143ffor gene expression, regulation of, 463f

for gluconeogenesis, 123ffor glycogen metabolism, 135ffor glycolysis, 107ffor glycoproteins, 171ffor glycosaminoglycans, 171ffor heme metabolism, 289ffor macronutrients, 370ffor monosaccharides, 89f

dietary, 143ffor NADPH, 155ffor nitrogen metabolism, 259ffor nucleotide metabolism, 305ffor obesity, 355ffor oxidative phosphorylation, 81ffor pentose phosphate pathway, 155ffor protein synthesis, 446ffor RNA structure and synthesis, 429fsymbols used in, 10ffor transcription, 429ffor triacylglycerol metabolism, 199ffor tricarboxylic acid cycle, 115f

Congenital adrenal hyperplasias (CAHs), 238,238f

Congenital disorders of glycosylation (CDG),167

Conjugation, 282Connective tissue proteins, 49. See also

Collagen; ElastinConsensus sequences

for DNA replication, 399for RNA transcription

eukaryotic, 423, 423fprokaryotic, 420, 420f

Constitutive genes, 449Cooley anemia, 39Cooperative binding

of oxygen, by hemoglobin, 29, 29fof single-stranded DNA-binding proteins,

400Cooperativity, of enzyme binding sites, 62–63Copper, Dietary Reference Intakes for, 358fCoproporphyria, hereditary, 280, 281fCoproporphyrin, 277Coproporphyrinogen III, 279fCoproporphyrinogen oxidase, 281fCoprostanol, 224Core enzyme, 419Core pentasaccharide, in oligosaccharides,

166, 166fCore protein, of glycosaminoglycans, 158,

160f, 161Cori cycle, 118, 118fCornea, collagen in, 43Coronary artery disease (CAD), 219Coronary heart disease

alcohol consumption and, 364–365dietary fats and, 360–361, 361fplasma lipids and, 360–361, 361fsoy protein and, 364triacylglycerols and, 361–362

Corticosteroid-binding globulin, 237Corticosteroids, 237, 237fCorticotropin-releasing hormone (CRH), 239Cortisol, 237, 237f

action of, 240fin hyperglycemia, 315f, 316prostaglandin synthesis inhibited by, 214secretion of, 239in transcriptional regulation, 456

Cosmids, 468Cosubstrates, 54Counterregulatory hormones, 313, 316Coupling reactions

common intermediates for, 72–73energy, 72–73, 72f

Covalent modificationof enzymes, 63, 64f

in absorptive/fed state, 321f, 322in fasting, 328–329glucagon in, 122, 122f

of proteins, 443f, 444, 444fCOX-1, 213, 214, 216fCOX-2, 213, 214C-peptide, in insulin synthesis, 308, 308f, 309fC-procollagen peptidases, 47Creatine, 287–288

degradation of, 287–288synthesis of, 287, 288f

Creatine kinase (CK), 65, 65fin creatine synthesis, 287

Creatine phosphate, 287, 288fCreatinine, 287, 288fCreutzfeldt-Jakob disease, 22, 23fCrigler-Najjar I and II, 282Cristae, of mitochondrion, 74Cyanocobalamin, 375, 376fCyanogen bromide, 16fCyanosis, chocolate, 38Cyclic adenosine monophosphate (cAMP), 94

actions of, 96fglucagon and, 314in glycogen degradation, 132–133, 133fglycogen synthesis inhibition by, 133–134,

134fhydrolysis of, 95–96, 96fas second messenger, 94–96, 291in triacylglycerol degradation, 190, 190f

3’,5’-cyclic AMP-dependent protein kinase,190

Cyclic AMP-independent PDH kinase, 110Cyclin-dependent kinases (Cdk), 407Cyclins, 407Cystathionine β-synthase, 273

deficiency in, 265, 273Cystathioninuria, 268f, 269fCysteine, 4

catabolism of, 263disulfide bonds of, 18f, 19side chains of, 3f, 4sulfhydryl group in, 18f, 19synthesis of, 265, 268

Cystic fibrosis (CF)ABC proteins and, 236mutation causing, 434pancreatic enzyme deficiency in, 174prenatal diagnosis of, 483, 483fsteatorrhea in, 177, 248

Cystic fibrosis transmembrane conductanceregulator (CFTR), 174, 434, 483

Cystinecatabolism of, 263disulfide bond in, 4, 18f, 19transport of, 250

Cystinosis, 249Cystinuria, 249f, 250, 268fCytidine, 292, 292fCytidine triphosphate (CTP)

NANA reaction with, 160synthesis of, 303, 303f

Cytochrome a + a3, 76Cytochrome b, 76, 76fCytochrome c, 25, 25f, 80Cytochrome oxidase, 76Cytochrome P450 (CYP), 279Cytochrome P450 (CYP) mixed-function

oxidase, 237Cytochrome P450 monooxygenase system,

149–150, 149fmicrosomal, 149–150


Index496

mitochondrial, 149Cytochrome(s)

in electron transport chain, 75f, 76Cytoplasm, cholesterol synthesis in, 220Cytosine, 291, 291f, 292f, 305f

in codons/genetic code, 431, 432fdamage to and repair of, 412, 413fpairing with guanine, 397, 397f, 398f

Cytosine arabinoside (cytarabine, ara C), 409,409f

Cytosol, 54fcholesterol synthesis in, 220oxaloacetate transport to, 119, 119fporphyrin synthesis in, 278transfer of acetyl CoA to, 183, 183f

DDactinomycin, 397, 421Darier disease (keratosis follicularis), 385dATP, 404D-configuration

of amino acids, 5, 5fdCTP, 404Deamination, oxidative

allosteric regulation of, 252of amino acids, 245, 252–253, 252fcoenzymes in, 252, 252fdirection of reactions, 252

“Debranching enzymes,” 128Decarboxylation

of cytosolic oxaloacetate, 119f, 120of histidine, 287, 287fof isocitrate, 112of oxaloacetate, 119f, 120oxidative

of α-ketoglutarate, 112, 112fthiamine and, 379, 379f

of branched-chain amino acids, 266thiamine and, 379f

of pyruvate, 105, 109–111, 110fDegeneracy, 4337-Dehydrocholesterol, 386, 386f7-Dehydrocholesterol-7-reductase, 221Dehydroepiandrosterone, 239Dehydrogenation, of branched-chain amino

acids, 266Denaturation

of DNA, 397–398, 398fof enzymes, 57of proteins, 20, 23f, 470

Deoxyadenosine, 292f5’-Deoxyadenosylcobalamin, 375, 376fDeoxycholic acid, 225Deoxyhemoglobin, 28Deoxyribonucleases, 397Deoxyribonucleoside phosphates, 291. See

also Nucleotide(s)5’-Deoxyribonucleoside triphosphate, 404Deoxyribonucleoside triphosphates (dNTPs),

470in polymerase chain reaction, 482

Deoxyribonucleotidessynthesis of, 297–298, 297f

regulation of, 297–298, 298f2-Deoxyribose, 292, 292fDeoxyribose-phosphate backbone, of DNA,

396–397, 396f, 397fzigzagging of, 398, 399f

Deoxyribose-phosphate lyase, 412Deoxythymidine, 292Dephosphorylation

of acetyl CoA carboxylase, 183–184

of enzymes, 63, 63fof fructose 1,6-bisphosphate, 120–121,

120fof glucose 6-phosphate, 121, 121fof hydroxymethylglutaryl (HMG) CoA

reductase, 223, 223fof proteins, 95of pyruvate kinase, 102sterol-independent, 223, 223f

Depot fat, 189Dermatan sulfate, 159f, 163Desmolase, 237, 238Desmosine cross-link, in elastin, 49, 49fDetoxification, in cytochrome P450

monooxygenase system, 149dGTP, 404Diabetes mellitus, 337–348

chronic effects and prevention of, 344–346concept map, 347fexcessive ketone bodies in, 197hemoglobin A1c in, 340, 340f, 346, 346fnutrition and, 361fsorbitol metabolism in, 345type 1 (insulin-dependent), 197, 337,

338–341, 347fautoimmune attack in, 338, 338fdiagnosis of, 338environmental stimulus for, 338, 338ffasting vs., 340genetic determinant for, 338, 338fintertissue relationships of, 338–339,

339fmetabolic changes in, 338–340, 338ftreatment of, 340–341, 340f

type 2 (non-insulin-dependent), 337,341–344, 347f

in children, 337exercise and risk of, 345–346, 346fgenetic determinant for, 338incidence and prevalence of, 337intertissue relationships of, 344, 345fmetabolic changes in, 344, 344fobesity and, 342, 342fprogression of glucose and insulin

levels in, 342–344, 342f, 343ftreatment of, 344typical progression of, 341–342, 344f

type 1 vs. type 2, 337fDiabetic ketoacidosis (DKA), 197, 197f, 339Diabetic nephropathy, 344f, 345

sorbitol metabolism and, 140Diabetic neuropathy, 344f, 345

sorbitol metabolism and, 140Diabetic retinopathy, 344f, 345

sorbitol metabolism and, 140Diacylglycerolacyltransferase, 176, 177fDiacylglycerol (DAG), 189f

activation of, 203, 203fin phospholipid synthesis, 201in signal transmission, 205–206

Diarrhea, osmotic, 87Diastereomers, 84Dicer, 459Dicumarol, 3892’,3’-Dideoxyinosine (didanosine, ddl), 409,

409fDideoxyribonucleoside triphosphates

(ddNTPs), 470Diet. See NutritionDietary Reference Intakes (DRIs), 357–358,

357fcomparison of components in, 358, 359f

guide to use, 358, 358fDieting, for weight reduction, 354Digestive enzymes

deficiencies of, 88diagnosis of, 88

Dihydrobiopterin, 268deficiency in, 270f

Dihydrofolate (DHF), 303Dihydrofolate reductase (DHFR), 267, 460

inhibition of, 293, 294f, 303, 375Dihydrolipoyl dehydrogenase, 110, 110fDihydrolipoyl transacetylase, 110, 110fDihydroorotase, 302Dihydroorotate dehydrogenase, 302Dihydropteridine (BH2) reductase, 270–271,

270fDihydropteridine (BH2) synthase, 270–271,

270fDihydrouracil, 292fDihydrouridine, 425fDihydroxyacetone, 83, 83fDihydroxyacetone phosphate (DHAP), 117,

189in fructose metabolism, 138isomerization of, 101

1,25-Dihydroxycholecalciferol, 240, 382, 3863,4-Dihydroxyphenylalanine (dopa), 285–286,

286fN6,N6-Dimethyladenine, 292f3,3-Dimethylallyl pyrophosphate (DPP), 2212,4-Dinitrophenol, 78f, 791,25-diOH cholecalciferol (calcitriol), 389Dipalmitoylphosphatidylcholine (DPPC), 204,

208Dipeptides, absorption of, 249Diphtheria toxin, 441fDipolar form, of amino acid, 7, 7fDisaccharidases, 86Disaccharide intolerance, 88Disaccharide(s), 83, 84f, 85

abnormal degradation of, 87–88dietary, 365digestion of, 86, 87in glycosaminoglycans, 157, 157fmetabolism of, 137–144

Dissociation constantof amino group, 7f, 8of carboxyl group, 7, 7f

Disulfide bonds, 4, 18f, 19, 297, 311–312Disulfiram, 317Diverticulosis and fiber, 366DNA, 395–416

annealing, in polymerase chain reaction,481–482

bases of, 396–397, 396fabnormal, removal of, 412, 412falteration of, 410–413hydrogen bonds between, 397, 398fpairing of, 396–397, 396fpurine, 291, 291f, 305fpyrimidine, 291, 291f, 305fspontaneous loss of, 410–413unusual, 291–292, 292f

B form of, 460chain elongation of, 403–405, 403fconcept map, 414–415fdenaturation of, 397–398

in polymerase chain reaction, 481double helix of, 397–398, 397f

antiparallel manner of, 397, 397faxis of symmetry for, 397, 397fbase pairing in, 397, 397fB form of, 398, 399f


Index 497

Chargaff’s Rules for, 397complementary nature of, 397, 397f,

398fA form of, 398major (wide) groove of, 397, 397fminor (narrow) groove of, 397, 397fstrand separation in, 397–398structural forms of, 398, 399fZ form of, 398, 399f

double-strand breaks in, repair of,412–413

double-stranded, 396eukaryotic

organization of, 409–410, 409f, 410freplication of, 406–409, 414f

for eukaryotic transcription, 422information flow from, 395, 395flinker, 410, 410fmelting temperature of, 397–398, 398fnucleoid, 398nucleoside analog inhibition of, 408–409,

409f3’→5’-phosphodiester bonds, 396–397,

396fplasmid, 398polarity of, 396prokaryotic, 395

See also Prokaryotic DNAreplication of, 399–406

proofreading of, 404–405, 404fregulation of gene expression through

modifications to, 460–461, 460f,461f

regulatory sequences of, 449–450renaturation (reannealing), 398repair of, 410–413, 415f

base excision, 412, 413fdouble-strand breaks, 412–413, 413fhomologous recombination, 413methyl-directed mismatch nucleotide

excision, 411-412, 411fnon-homologous end-joining, 413

single-stranded (viral), 396structure of, 396–398, 414fas template for RNA, 417. See also RNA,

synthesis (transcription) ofultraviolet damage to, 412, 412fvariations in, resulting in restriction

fragment length polymorphisms,475, 475f, 476f

Z form of, 460DNA analysis, 15–16, 473–485, 485f. See

also specific methodsforensic, 482–483techniques for, 485f

DnaA protein, 399DnaB, 400DnaC, 400DnaG, 402DNA-binding motifs, 423DNA-binding site, 450, 450fDNA cloning, 467–470, 468f

libraries of, 469–470sequencing of fragments in, 470, 471fvectors, 467–468, 470f

expression, 470, 470fDNA fingerprinting, 482–483DNA fragments

blunt ends of, 466, 466fcloned, sequencing of, 470, 471fhybridization of probes to, 470sticky ends of, 466, 466f

joining of (recombinant DNA), 467f

DNA gyrase, 401DNA helicases, 400, 400f, 406DNA hybridization, 475DNA libraries, 469–470

complementary, 469–470, 469fgenomic, 469

DNA ligase, 406, 406fin DNA repair, 412restriction endonucleases and, 466

DNA microarrays, 483–484, 484f, 485fDNA polymerase I, 405, 406, 406f

in DNA repair, 411DNA polymerase III, 403–404, 404f, 405,

406in chain elongation, 403–405, 404fin proofreading, 404–405, 404f

DNA polymerase(s), 4213’→5,’ in DNA proofreading, 404f, 405chain elongation and, 403–404, 404f5’→3’ DNA polymerase, 404–405, 404fin DNA repair, 411, 412eukaryotic, 407, 407fin polymerase chain reaction, 480–482sequencing cloned DNA fragments

and, 470, 471fDNA probes, 465, 465f, 470–472

antibodies, 472biotinylated, 472hybridization to DNA fragments, 470oligonucleotide, 471–472, 472f

in sickle cell disease, 472, 472f,473f

DNA sequencing. See also DNA analysisof protein’s primary structure, 15–16

DNA topoisomerase(s), 401type I, 401, 421type II, 401

Docosahexaenoic acid (DHA), 363Dolichol, 167Dolichol-linked oligosaccharide, synthesis

of, 167Domains, of polypeptides, 19Dopamine, in catecholamine synthesis,

286, 286fDopamine β-hydroxylase, 286Double helix, of DNA, 395, 397–398, 397f

antiparallel manner of, 397, 397faxis of symmetry for, 397, 397fbase pairing in, 397, 397fB form of, 398, 399fChargaff’s Rules for, 397complementary nature of, 397, 397fA form of, 398major (wide) groove of, 397, 397fminor (narrow) groove of, 397, 397fstrand separation in, 397–398structural forms of, 398, 399fZ form of, 398, 399f

Double-reciprocal plot, of enzyme action,59, 59f

Down-regulation, 313Drug absorption, Henderson-Hasselbalch

equation for, 9, 9fdsRNA, RNA interference and, 459D-sugar, 84, 84fdTTP, 404Dubin-Johnson syndrome, 283Duchenne muscular dystrophy, 461Duodenum, dietary lipid emulsification in,

175Dyslipidemia. See also

Hyperlipidemia/hyperlipoproteinemia

obesity and, 353Dystrophin gene, 486

EEcoRI, 466fEdman degradation, 15, 15fEhlers-Danlos syndrome (EDS), 48, 48fEicosanoids, 213Eicosapentaenoic acid (EPA), 363Elastase, 249fElastase, inhibition of, 50, 50f

deficient, and emphysema, 50Elastin, 43, 49–51

concept map, 51fdegradation of, 50

α1-antitrypsin in, 50, 50fdisorders of, 50, 51f

desmosine cross-link in, 49, 49ffunction of, 43mechanical properties of, 43structure of, 49, 49f

Electrical gradient, in oxidativephosphorylation, 77–79

Electrolyte(s), amphoteric, 9Electron acceptors, 74, 76Electron donors, 74, 76Electron transport chain, 73–77, 75f

ATP phosphorylation in, 77–80coenzyme Q in, 75–76coupled to proton transport, 77–78, 78fcytochromes in, 75f, 76free energy release during, 76–77NADH dehydrogenase in, 75, 75fNADH formation in, 75, 75forganization of, 74, 75freactions of, 75–76, 75f, 76fsite-specific inhibitors of, 76, 76ftightly coupled with oxidative

phosphorylation, 77–78uncoupling from phosphorylation,

78–79Electrophoresis, in sickle cell disease, 36,

36fElectrophoretic mobility

of low-density lipoproteins, 227, 228fof plasma lipoproteins, 227, 228f

Emphysema, α1-antitrypsin deficiency and,50, 51f

Enalapril, 62Enantiomers, 84, 84f, 85fEndergonic reactions, 70Endocrine signaling, 94fEndocytosis

of chylomicrons remnants, 230–231of glycosphingolipids, 210of intermediate-density lipoproteins,

231of low-density lipoproteins, 232, 233freceptor-mediated, 232, 233f

Endoglycosidases, 86Endonuclease(s), restriction, 405,

465–466, 465fnomenclature for, 466restriction sites, 466specificity of, 465–466, 466f“sticky” and “blunt” ends, 466, 466f,

467fEndopeptidase, 15, 249Endoplasmic reticulum

cholesterol synthesis in, 220rough

apolipoprotein synthesis in, 228collagen precursors in, 45, 46f


Index498

glycoprotein synthesis in, 166, 167,167f, 168f

ribosomes in, 436–437smooth, cytochrome P450

monooxygenase system of, 149Endothelium-derived relaxing factor, 151. See

also Nitric oxideEnd-product inhibition, 293Energy

ATP as carrier of, 72–73content in food, 359, 359ffree, 55. See also Free energy

of activation, 55, 55fchange in, 70–72, 70fstandard, change in, 71–72, 71f

production ofin tricarboxylic acid cycle, 113, 113f

requirements in humans, 358–360use in body, 359–360, 359f

Energy barrier, in reactions, 55Energy coupling, 72–73, 72fEnergy metabolism, integration of, 307, 307f,

319fEnergy yield

from fatty acid oxidation, 192, 193ffrom glycolysis, 104from oxidation of fatty acids, 189, 192, 193f

Enhancers, in eukaryotic gene regulation, 424,424f

Enolase, 102eNOS, 151Enoyl CoA hydratase, 192f3,2-Enoyl CoA isomerase, 195Enteral feeding, 369Enterocytes

chylomicron assembly in, 228enzymes synthesized by, carbohydrate

digestion by, 86–87, 87flipid absorption by, 176lipid secretion from, 177–178monosaccharide absorption by, 87

Enterohepatic circulation, 225–226, 226fEnterohepatic urobilinogen cycle, 283–284,

283fEnteropeptidase (enterokinase), 248Enthalpy, 69, 69fEntropy, 69, 69fEnvironmental factors, in obesity, 352Enzyme kinetics curve, 57, 57fEnzyme-linked immunosorbent assays

(ELISAs), 484, 485fEnzyme-product (EP) complex, 54Enzyme replacement therapy (ERT), 163, 301,

472Enzyme(s), 53–68. See also specific enzymes

in absorptive/fed state, 321–322, 322factivation of, 55, 55factive sites of, 54, 54f

chemistry of, 56ionization of, 57

allosteric, 57, 67fin committed (rate-limiting) step of

pathway, 62effectors or modifiers of, 62–63, 62f, 64fsigmoidal kinetics curve of

57, 62f, 63in alternate reaction pathway, 55biotin-linked, 444, 444fcatalytic efficiency of, 54

factors in, 56changes in fasting, 328–329in clinical diagnosis, 64–66cofactors for, 54

compartmentalization of, 55concept map, 67fcore, 419degradation of, 64fdenaturation of, temperature and, 57dephosphorylation of, 63, 63fenergy changes and, 55, 55fin fatty acid oxidation of fatty acyl CoA,

192first-order reactions of, 59, 59ffunctions of, 53inhibition of, 55, 60–62

competitive, 60–61, 60ffeedback, 63, 63firreversible, 60noncompetitive, 61–62, 61f, 62freversible, 60

inhibitors of, as drugs, 62IUBMB classification of, 53, 53flocation within cell, 54f, 55mechanism of action, 55–56

Lineweaver-Burke plot of, 59, 59fMichaelis-Menten equation for, 58–59nomenclature for, 53

recommended name, 53systematic name, 53, 53f

pancreatic, 175–176pH optimum for, 58, 58fphosphorylation for, 63, 63fplasma assays of, 65properties of, 54–55as protein catalysts, 54reaction velocity of

competitive inhibition and, 60–61, 60fconcentration of enzyme and, 59, 60ffactors affecting, 56–58hyperbolic kinetics curve of, 57, 57finitial, 57maximal (Vmax), 57, 57fnoncompetitive inhibition and, 61–62,

61fpH and, 57–58, 58fsubstrate concentration and, 57, 57f,

58f, 59ftemperature and, 57, 57f

regulation of, 55, 62–64, 64fallosteric, 62–63, 62f, 64fby covalent modification, 63, 63f, 64f,

321f, 322by product inhibition, 64fby substrate inhibition, 64f

salvage, 409serum assays of, 65specificity of, 54synthesis of, induction and repression of,

63–64, 321f, 322in absorptive/fed state, 321–322, 322fin fasting, 328–329

in synthesis of glycosphingolipids, 210transition state and, 56, 56fturnover number of, 54zero-order reactions of, 59, 59f

Enzyme-substrate (ES) complex, 54Enzyme substrates, 53Epimers, 83–84, 84fEpinephrine

in acetyl CoA carboxylase regulation, 183,184f

in catecholamine synthesis, 285–286,286f

degradation of, 286, 286fin diabetes mellitus, 341in energy metabolism, 307in fasting, 331functions of, 285

glucagon secretion and, 313, 313fglycogen metabolism and, 132, 133f, 134,

134fin hyperglycemia, 315f, 316in hypoglycemia, 315, 315finsulin and, 310, 310fin integration of metabolism, 307synthesis of, 286, 286fin triacylglycerol degradation, 190f

Epithelial cells, vitamin A and, 384Equilibrium, zero free energy change in, 70Equilibrium constant (Keq), relationship with

standard free energy change, 71–72Ergocalciferol, 386, 386fErythrocyte-producing cells, heme synthesis

in, 278–279Erythromycin, 441fErythropoietic porphyrias, 280, 281fErythropoietin, heme synthesis and, 279Escherichia coli

DNA replication in, 399–406lactose operon of, 450–452, 451fprotein synthesis in, 440–441fregulation of gene expression in, 450–454Shine-Dalgarno sequence, 439, 454

E sites, on ribosome, 436Eskimos, lactose intolerance in

88Essential amino acids, 261, 262f, 367

in protein synthesis, 434Estimated Average Requirement (EAR), 357,

358fEstimated Energy Requirement, 358Estradiol, 237f, 238f, 239Estrogens, 237, 239, 240fEthanol

porphyria and, 280pyruvate reduced to, 105, 106fsecondary hyperuricemia and, 301

Ethanolamine, synthesis ofphosphatidylethanolamine and,203–204

Ether-linkagein plasma-activating factor, 202, 202fin plasmalogens, 202, 202f

Etoposide, 401Euchromatin, 422, 460Eukaryotic cell cycle, 406–407, 407fEukaryotic DNA, 399, 400f

chain elongation of, 403–405, 403forganization of, 409–410, 409f, 410freplication of, 406–409

therapeutic inhibition of, 408–409,409f

Eukaryotic gene expression, regulation of,449, 449f, 449f, 454–461, 463f

Eukaryotic gene transcription, 422–424enhancers in, 424, 424fpromoters in, 422–423, 423f

Eukaryotic mRNA, 425–427, 426fEukaryotic translation initiation factor (eIF2),

460, 460fExercise

development of type 2 diabetes and,345–346, 346f

energy expenditure and, 359f, 360weight reduction and, 354

Exergonic reactions, 70Exons, 426Exonuclease, 4053ʼ→5ʼ exonuclease, 4073ʼ→5ʼ-exonuclease, 404f, 405Exopeptidase, 15, 249Expression library, 472Expression vector, 470, 470f


Index 499

Extracellular matrix (ECM)collagen in, 43collagen precursors in, 45glycosaminoglycans in, 157

Ezetimibe, 176

FFabry disease, 211, 212f, 213FAD. See Flavin adenine dinucleotideFADH2, 73, 73f, 76

production of, in fatty acid oxidation, 192,193f, 195

in tricarboxylic acid cycle, 112f, 113Familial dysbetalipoproteinemia, 178, 231Familial hypercholesterolemia, 232Familial lipoprotein lipase deficiency, 178, 229Familial type III hyperlipoproteinemia, 231Farber disease, 212fFarnesylated protein, 444, 444fFarnesyl pyrophosphate (FPP), 221Fast/fasting, 327–329

adipose tissue in, 331, 331fbrain in, 332, 332f, 333fenzymic changes in, 328–329, 328ffuel stores at beginning of, 327, 329fgluconeogenesis regulation by, 123, 123fglycogen in, 329, 329fglycogen stores and, 126, 131, 135fhypoglycemia in, 317intertissue relationships of, 334fketoacidosis and, 197kidney in long-term, 332liver in, 329–331, 330fpyruvate carboxylase in, 196pyruvate dehydrogenase in, 196resting skeletal muscle in, 331–332, 332f

Fasting blood glucose (FBG), 338Fasting hypoglycemia, 317Fat metabolism

in absorptive/fed stateadipose tissue, 325, 325fcerebral, 327, 327fhepatic, 323f, 324resting skeletal muscle, 326, 326f

in fastingadipose tissue, 331, 331fhepatic, 330–331, 330f

Fat(s)body, deposition of


depot, 189dietary, 360–365



effects of, 364fenergy content of, 359, 359fmonounsaturated, 361–362, 362fplasma cholesterol and, 364plasma lipids and, 361–364polyunsaturated, 362–363, 362fsaturated, 361, 362f

metabolism ofin absorptive/fed state, 323f, 324, 325,

325f, 326, 326f, 327, 327fin fasting, 330–331, 330f, 331, 331f,

332, 332fneutral, 188stored, mobilization of, 189–195

Fat-soluble vitamins, 373, 373f, 392–393fFatty acid α-hydroxylase, 195Fatty acid CoA synthetases (thiokinases), 189Fatty acid cyclooxygenase (COX), 213

Fatty acid(s), 173fin absorptive/fed state, 323f, 324, 325,

325famphipathic nature of, 181branched-chain, 195, 195fchain lengths of, 182cis, 363fcis double bonds of, 182, 182fcommon names of, 182, 182fdegradation of, 181f, 194f

in diabetes mellitus, 197de novo synthesis of, 183–189

NADPH sources for, 186, 186frate-limiting step of, 183–184, 184frelationship with glucose metabolism,

186, 187fdesaturation of, 188dietary


monounsaturated, 361–362, 362f, 364fpolyunsaturated, 362–363, 362f, 364fsaturated, 361, 362f, 364f

elongation of, 187essential, 182esterified, 181even-numbered, saturated, 194fin fasting, 331, 331ffate of, 189free (unesterified), 181


fate of, 178metabolism of, 173–180oxidation ofas product of lipid degradation,

175–176transport of, 190

as fuel source for resting skeletal muscle,332

long-chain (LCFA), 181transport into mitochondria, 190–192,

191fmelting temperature of, 182metabolism of, 181–200, 181f, 199fmonounsaturated, 182, 361

oxidation of, 195n-3 (omega-3), 182, 363, 364fn-6 (omega-6), 183, 363, 364fwith odd number of carbons, oxidation of,

193–195, 195foxidation of

α, 195, 195fβ, 190–195, 191f, 192fdisorders in, 192energy yield of, 189, 192, 193fenzymes involved in, 192fin fasting, 330, 330fmitochondrial pathway for, 190–192,

191fin peroxisome, 195UCP1 (thermogenin) in, 79

plasma, 181polyunsaturated, 182, 188as prostaglandin precursor, 181resynthesis of, 176–177saturation of, 182, 182f, 361short- and medium-chain, transport into

mitochondria, 192storage of, 188–189, 188fstored, mobilization of, 189–195as structural components, 181structure of, 181–182, 181ftrans, 363–364, 363f, 364ftransport of, 190–192

as triacylglycerol component, 181–183,188–189

release of, 190unsaturated, 182, 182f

oxidation of, 195very long-chain, 187

oxidation of, 195Fatty acid synthase, 184–186, 185f, 187

pantothenic acid in, 381Fatty acyl CoA

enzymes in β-oxidation of, 192, 192flong-chain, 183in phosphatidic acid synthesis, 189fin triacylglycerol synthesis, 189, 189f

Fatty acyl CoA dehydrogenase, 193Fatty acyl-CoA synthetase (thiokinase), 176Fatty acyl CoA transferase, 208Fatty liver, 23, 3181Favism, 153Favorable processes, 72f, 73F-cell, 33 Febuxostat, 301Fecal sterols, neutral, 224Fed state, 321–327

adipose tissue in, 324–325carbohydrate metabolism in, 325, 325ffat metabolism in, 325, 325f

allosteric effectors in, 321, 321fbrain in, 326–327

carbohydrate metabolism in, 327, 327ffat metabolism in, 327, 327f

concept map, 335fcovalent modification in, 321f, 322enzymic changes in, 321–322, 321fglycogen stores in, 126, 131, 135fglycolysis in, 100, 100f, 323, 323f, 325,

325finduction-repression of enzyme synthesis

in, 321f, 322intertissue relationships in, 328fliver in, 322–324, 323f

amino acid metabolism in, 323f, 324carbohydrate metabolism in, 322–324,

322ffat metabolism in, 322f, 323f, 324

resting skeletal muscle in, 325–326amino acid metabolism in, 326, 326fcarbohydrate metabolism in, 326, 326ffat metabolism in, 326, 326f

substrate availability in, 321, 321fFeedback inhibition, 63, 63fFeed/fast cycle, 321–336. See also

Fast/fasting; Fed stateconcept map, 335f

Feed-forward regulation, 102FEN1, 406Ferrochelatase, 62, 279, 281fFerrous iron (Fe2+), in heme, 25, 25fFetal hemoglobin (HbF), 33, 33f

binding of 2,3-BPG to, 33in β-thalassemia, 38–39, 38fsynthesis of, 33, 33f

α-Fetoprotein, detection of, 476Fetoscopy, 476Fiber

dietary, 365–366, 366facceptable distribution ranges for, 360factions of, 366, 366f

functional, 366insoluble, 366soluble, 366total, 366

Fibrates, 226Fibril-associated collagens, 44, 44fFibril-forming collagens, 44, 44f


Index

Fibrillingene, mutation, and Marfan’s syndrome,

49tropoelastin interaction with, 49

Fibrous proteins, 43–52. See also Collagen;Elastin

concept map, 51fsummary, 52

Fight-or-flight reactions, 285, 307First-order reactions, 59, 59fFischer projection formula, 84, 85fFish oil, 363, 363fFlanking sequences, 481Flavin adenine dinucleotide (FAD), 73,

380–381, 380fas coenzyme

for branched-chain α-ketoaciddehydrogenase, 266

for α-ketoglutarate dehydrogenasecomplex, 112

for NADPH oxidase, 150for nitric oxide synthase, 151for pyruvate dehydrogenase complex,

110, 110fin fatty acid oxidation, 195in mitochondrial matrix, 74reduced form of, 76, 380–381. See also

FADH2in tricarboxylic acid cycle, 112–113, 112f

Flavin mononucleotide (FMN), 75, 380–381,380f

as coenzyme, for nitric oxide synthase,151

in electron transport chain, 75, 75fin nitric oxide synthesis, 151oxidation of NADH by, 76, 77freduced form of (FMNH2), 381

in electron transport chain, 75, 75fFluoride, Dietary Reference Intakes for, 358fFluoroacetate, 112Fluorocitrate, 1125-Fluorouracil, 303Fluvastatin, 224FMN. See Flavin mononucleotideFMNH2, 381

in electron transport chain, 75, 75fFoam cells, 234, 235fFolate trap hypothesis, 376Folic acid analogs

action of, 374–375, 374fdihydrofolate reductase inhibited by, 374f,

375purine synthesis inhibited by, 294f, 295,

374f, 375Folic acid (folate), 262, 265, 374–375

active form of (tetrahydrofolic acid), 392fin one-carbon metabolism, 267, 267fin thymidine monophosphate

synthesis, 303–304, 304f,374

in amino acid metabolism, 267as carrier of “one-carbon” units, 267deficiency of, 267

anemia and, 374–375, 374fdiagnosis of, 262neural tube defects and, 375

dietary intake ofcardiovascular risk and, 265, 265fDietary Reference Intakes for, 358f

function of, 374, 392fin homocystinuria, 273structural analogs of, 293, 294fsupplementation of, 375synthesis of, drug inhibiting, 374–375,

374f

Vitamin B12 deficiency and, 375, 377Follicle-stimulating hormone (FSH), 239f, 240Food

energy content in, 359thermic effect of, 359

Forensic analysis of DNA samples, 482–483Formaldehyde, 267Formic acid, 182f

as one-carbon unit, 267N-Formiminoglutamate (FIGIu), 262N10-Formyltetrahydrofolate, 292, 293, 439Forssman antigen, 209Forward reactions, free energy change in, 70Fragile X syndrome, 433, 433fFrame-shift mutations, 434, 434fFree amino acid, 1, 1fFree energy, 69, 69f

of activation, 55, 55fcatalyzed vs. uncatalyzed, 55, 55flower, in alternate reaction pathway,

55change in, 70–72

coupling of negative and positive, 70in forward and backward reactions, 70negative, 70, 70fpositive, 70, 70fas predictor of reaction direction, 70reactant and product concentrations

and, 70–71, 71frelationship with enthalpy and entropy,

69, 69fzero, in equilibrium, 70

release, during electron transport, 76–77standard, change in, 71–72

additivein consecutive reactions, 72in pathways, 72

in ATP hydrolysis, 73as predictor under standard

conditions, 71relationship with Keq, 71–72relationship with standard reduction

potential, 77Free radicals, oxygen-derived, 150Fructokinase, 137

deficiency of, 138in fructose phosphorylation, 137–138,

138fFructose, 83, 365

absorption of intestinal mucosal cells, 87dietary intake of, 365dietary sources of, 137glucose conversion to, via sorbitol,

139–140as isomer, 83, 84fmetabolism of, 137–140, 137f, 139f

concept map, 143fdisorders of, 138kinetics of, 138

phosphorylation of, 137–138, 138fFructose 2,6-bisphophonateFructose 1,6-bisphosphatase, 99, 120–121,

120f, 122, 123in absorptive/fed state, 321, 322f, 324in fasting, 329

Fructose 1,6-bisphosphatecleavage of, 100, 100fdephosphorylation of, 120–121, 120fin gluconeogenesis, 120–121, 120fin glycolysis, 100, 101fin pyruvate kinase regulation, 102regulation of

by energy levels within cell, 120–121by fructose 2,6-bisphonate, 120f, 121by glucagon levels, 120f, 121

Fructose 2,6-bisphosphatein absorptive/fed state, 321in fructose 1,6-bisphosphonate regulation,

120f, 121glucagon and, 121insulin and, 100, 100fin phosphofructokinase-1 regulation, 99,

100fFructose intolerance, 301Fructose 1-phosphate

cleavage of, 138, 139ffructose conversion to, 138

Fructose 6-phosphate, 147in amino acid synthesis, 161, 161fglucokinase regulated by, 98–99isomerization of glucose-6-phosphate to,

99, 99fmannose conversion to, 138in pentose phosphorylation pathway, 147,

147fphosphorylation of, 99–100, 100f

Fructose 1-phosphate aldolase, 138Fructosuria, essential, 139fL-Fucose (Fuc), 166Fumarase (fumarate hydratase), 113Fumarate

amino acids that form, 263, 263fhydration of, 112f, 113succinate oxidation to, 112f, 113in urea cycle, 253–255, 254f

Furanose, 84

GGalactocerebroside, 209, 209fGalactocerebroside 3-sulfate, 210, 210fGalactokinase, 140

deficiency of, 141f, 142D-Galactosamine, 157Galactose

absorption by intestinal mucosal cells, 87attached to UDP, 140–141, 141f

in biosynthetic reactions, 141as carbon source for glycolysis or

gluconeogenesis, 140–141dietary sources of, 140epimers, 83–84as isomer, 83, 84fin lactose, 142metabolism of, 137f, 140–142, 141f

concept map, 143fdisorders of, 141–142, 141f

phosphorylation of, 140Galactosemia

classic, 141, 141fgalactokinase deficiency and, 141f, 142

Galactose 1-phosphate, 140Galactose 1-phosphate uridyltransferase, 140,

141, 141fβ-Galactosidase (lactase), 87, 450

deficiency of, 140, 141β-D-Galactosyltransferase, 142Gallstones, 226–227, 226fGangliosides, 209–210, 209fGangliosidosis, GM1, 212fGastric-inhibitory polypeptide (GIP), 310Gastric juice, 248Gastric lipase, 173, 174Gastrointestinal hormones. See also

Cholecystokinin; Secretininsulin secretion and, 310

Gaucher disease, 211, 211f, 212f, 213, 472Gemfibrozil, 226Gene chip, 484Gene expression

500


Index 501

analysis of, 483–485DNA microarrays of, 483–484, 484fenzyme-linked immunosorbent

assays, 484, 485fHIV, detecting exposure to, 484,

485fnorthern blots, 483proteomics, 485western blots, 484, 485f

regulation of, 449, 449fconcept map, 463feukaryotic, 449, 449f, 454–461,

463fprokaryotic, 449f, 450–454, 463f

Gene replacement therapy, 485, 486fGenes, housekeeping, 449Genes, constitutive, 449Gene therapy, 485, 486fGenetic code, 431–434

characteristics of, 432–433for codon translation, 431, 432fdegenerate, 432f, 433nonoverlapping and commaless, 433redundancy of, 433specificity of, 432universality of, 432, 432f

Genetic factors, in obesity, 352, 352fGene transcription

eukaryotic, 422–424combinatorial control of, 455, 455fenhancers in, 424, 424fpromoters in, 422–423, 423fregulation of, 449, 454–461

hormone response elements and, 240,241f

prokaryotic, 419–421antibiotics targeting, 421, 422felongation in, 420–421, 420fhairpin turn in, 421, 421finitiation of, 419–420, 420fregulation of, 449, 450–454termination of, 421, 421f

Genome, human, 465Genomic DNA libraries, 469Geranyl pyrophosphate (GPP), 221Gestational diabetes, 338, 342Ghrelin, 353, 353fGilbert syndrome, 282Globin-like genes, 34Globin(s). See also Hemoglobin(s);

Myoglobinβ, 427βS-globin mutation

detecting, 472, 473f, 477, 478chains, synthesis of, 35, 35fgenes

α, 34, 34f, 35fβ, 34f, 35, 35fδ, 35ε, 35γ, 35organization of, 34–35, 34fζ, 35

Globoid cell leukodystrophy, 212fGlobosides, 209Globular proteins, 25–42. See also

Hemoglobin; Myoglobinin aqueous solution, 18tertiary structure of, 18–20

Glucagon, 307, 313–314, 319fin absorptive/fed state, 321in acetyl CoA carboxylase regulation,

183, 184fallosteric effectors and, 122

carbohydrate metabolism and, 314composition of, 313concept map, 319fcovalent modification of enzyme activity

by, 122, 122fin diabetes mellitus, 341fructose 1,6-bisphosphate and, 121gluconeogenesis and, 122glycogen metabolism and, 132–133,

133fglycolysis and, 105, 105fin HMG CoA reductase regulation, 223in hyperglycemia, 315f, 316in hypoglycemia, 315, 315f, 316induction of enzyme synthesis by, 122insulin action composed by, 313, 319fin integration of metabolism, 307lipid metabolism and, 314mechanism of action, 314, 314fmetabolic effects of, 314protein metabolism and, 314secretion of, 313–314

amino acids and, 313, 313fcoordination with insulin secretion,

309, 313epinephrine and, 313, 313fglucose and, 313, 313finhibition of, 313f, 314stimulation of, 313–314

synthesis of, 313in transcriptional regulation, 456triacylglycerols and, 190

Glucoamylase, 87Glucocerebroside, 209Glucocorticoid receptors, 456Glucocorticoid response element (GRE),

456Glucocorticoids, 237Glucogenic amino acids, 261, 262f, 266Glucokinase

in glucose phosphorylation, 98–99, 98f,99f

in absorptive/fed state, 322, 323fhexokinase vs., 98insulin and, 99, 105, 105f, 310, 313kinetics of, 98, 98fregulation of, 98–99, 99f, 105, 105f

Gluconeogenesis, 102, 117–124, 117f, 125in absorptive/fed state, 323–324allosteric activation of acetyl CoA and,

119allosteric inhibition by AMP and, 121concept map, 123fCori cycle and, 118, 118fethanol consumption and, 317, 317fin fasting, 329–330, 330fglucagon levels and, 121–122glycolysis vs., reactions favoring, 117,

121reactions unique to, 118–121regulation of, 121–122relationship to other metabolic

reactions, 117fsubstrates for, 117–118

availability of, 122UDP-galactose as carbon source for,

140–141, 141fGlucopyranose, 84Glucoregulatory systems, 315f, 316β–Glucuronidase deficiency, 164fD-Glucosamine, 157Glucosamine-N-acetyltransferase

deficiency, 164fGlucose, 365


in absorptive/fed state, 321α-D, in glycogen, 126anomeric forms, 85fattached to uridine diphosphate (UDP-

glucose), 126–127, 127fblood, dietary carbohydrates and, 366,

366fbrain requirements for, 327, 332breakdown of. See Glycolysisin collagen, 45conversion to fructose, 139–140, 140fconversion to pyruvate, 96–103in diabetes mellitus, 342, 343fdietary carbohydrates and, 366, 366fdietary intake of, 365

blood glucose levels and, 366, 366felevated blood levels of, 337. See also

Diabetes mellitusenantiomers, 85fas energy source, 125epimers, 83–84, 84fin fasting, 329–331, 330f, 332, 333fformation of. See Gluconeogenesisglucagon secretion and, 313, 313fhypoglycemia and, 314, 315fin insulin secretion, 310, 310fisomers of, 83, 84fin lactose, 142low blood levels of, 314–318. See also

Hypoglycemiaregulatory systems activated by,

315f, 316metabolism of, relation to palmitate

synthesis, 186, 187fin normal weight and obese subjects,

342, 342fphosphorylation of, 98–99, 98f

in absorptive/fed state, 322glucokinase in, 98–99, 98f, 99fhexokinase in, 98, 98f

in regulation of gene expression, 451f,452, 452f

sources of, 125storage of, 125synthesis of. See Gluconeogenesisin transcription from bacterial operons,

452transport of

in absorptive/fed state, 325, 325f,326, 326f

into cells, 96–97characteristics of, 312, 312fin fasting, 331, 332finsulin and, 312, 312fNa+-independent facilitated

diffusion, 96–97, 97fNa+-monosaccharide cotransporter

system of, 96, 97Glucose-alanine cycle, 253Glucose 1,6-bisphosphate, 126, 130Glucose 6-phosphatase, 121, 130, 457

deficiency of, 130fin fasting, 329, 332

Glucose 1-phosphateconversion to glucose 6-phosphate,

130Glucose 6-phosphate

in absorptive/fed state, 326dehydrogenation of, in pentose

phosphate pathway, 145–146,146f


Index502

dephosphorylation of, 121, 121fin fasting, 331in gluconeogenesis, 121from glucose 1-phosphate, 130in glycolysis, 98–99hexokinase inhibited by, 98isomerization of, 99, 99f

Glucose 6-phosphate dehydrogenase, 148deficiency in, 103, 152–154, 153f

G6PD A-, 153Mediterranean, 153, 153f, 154precipitating factors in, 153variants of, 153, 153f

molecular biology of, 154in red blood cells, role of, 152–153, 152f

Glucose 6-phosphate dehydrogenase(G6PD), 145–146

Glucose 6-phosphate translocase, 121, 130deficiency of, 130f

Glucose tolerance test, 338Glucose transporters, 97, 97f

GLUT-1, 97GLUT-2, 98, 310, 311

in absorptive/fed state, 322, 323fGLUT-3, 97GLUT-4, 97GLUT-5, 97GLUT-7, 97GLUT-14, 97insulin-sensitive, 312, 312fisoforms of, 97

specialized functions of, 97α(1→4)-Glucosidase (acid maltase), 130

deficiency in, 129fGlucuronic acid, 150, 161D-Glucuronic acid, 157, 157f, 161β-Glucuronidase, deficiency in, 164fGlutamate dehydrogenase, 252–253, 252f,

256, 262allosteric regulators of, 252coenzymes of, 252, 252fin fasting, 332

Glutamate (glutamic acid), 19fα-helix disrupted by, 16–17in amino acid deamination, 252–253, 253fcarboxylation of, 389, 389fcatabolism of, 262degradation of proteins containing, 247as product of transamination, 250–252,

251fas proton donor, 5replacement of

by lysine, in hemoglobin C disease,36f, 37

by valine, in sickle cell disease, 36,36f

side chains of, 3f, 5carboxylate group in, 5

synthesis of, 267–268, 268fin urea cycle, 253–256

Glutamate:oxaloacetate transaminase (GOT). See Aspartateaminotransferase (AST)

Glutamate pyruvate transaminase (GPT).See Alanine aminotransferase (ALT)

Glutamate semi-aldehyde, 262Glutaminase, 253, 253f, 256, 256f, 257

in fasting, 332intestinal, 256renal, 256

Glutamineammonia from, 256–257, 256fin ammonia transport, 257, 257fas atom source for purine ring, 292, 293fas atom source for pyrimidine ring, 302,

302fcatabolism of, 262side chains of, 3f, 5synthesis of, 256f, 268

Glutamine:phosphoribosylpyrophosphateamidotransferase, 293, 296

Glutamine synthase, 257, 257fGlutamine synthetase, 253, 253f, 268γ-Glutamylcysteinylglycine, 148Glutathione, 152

as antioxidant, 148structure of, 148, 148f

Glutathione peroxidase, 148, 150Glutathione reductase, 148Gluten (gliadin), 249Glycation, 168Glycemic control, in diabetes mellitus,

345–346, 346fGlycemic index, 366, 366fGlycemic load, 366Glycemic response, 366Glyceraldehyde, 83, 83fGlyceraldehyde 3-phosphate, 96, 111, 161

oxidation of, 101, 101fin pentose phosphate pathway, 147

Glyceraldehyde 3-phosphate dehydrogenase,101, 103

Glycerolfate of, 178, 190as gluconeogenic precursor, 117oxidation of, 117in phospholipids, 201–202, 201fphosphorylation of, 117

Glycerol kinase, 117, 189, 190in absorptive/fed state, 325

Glycerol phosphatein phosphatidic acid synthesis, 189fsynthesis of, 188f, 189in triacylglycerol synthesis, 189, 189f

Glycerol 3-phosphate, 311, 324Glycerol phosphate dehydrogenase, 76, 80,

117, 189, 190Glyceroneogenesis, 190, 331Glycerophosphate shuttle, 79f, 80Glycerophospholipids, 201–202, 201f

antigenic, 202degradation of, 207–208, 207fsynthesis of, 201f, 202

Glycerylphosphoryl-base, 176Glycine

as atom source for purine ring, 292, 293fin β-bends, 17bile acids conjugated to, 225, 225fcatabolism of, 263, 263fin collagen, 45in creatine synthesis, 287, 288finterconversion with serine, 263, 263f, 268optical properties of, 5in porphyrins, 278side chains of, 2fsynthesis of, 268

Glycochenodeoxycholic acid, 225, 225fGlycocholic acid, 175, 175f, 225, 225fGlycogen, 84, 85

allosteric regulation of, 131–132, 131fbranches of

formation of, 128removal of, 128–130

chains ofelongation of, 127shortening of, 128

degradation of (glycogenolysis), 125, 125f,128–131, 129–130f

AMP and, 132

calcium and, 131–132, 132fcAMP-directed pathway and, 132–133in fasting, 329, 329flysosomal, 130–131regulation of, 131–134, 133f

in fasting, 126, 131, 135fduring fed state, 126, 131, 135fas fuel source for resting skeletal muscle,

332fuel stores of, before fast, 329, 329ffunction of, 125–126hepatic, 125–126, 131fhormonal regulation of, 133–134, 134fmetabolism of, 125–136

concept map, 135fmuscle, 125–126, 131fstorage of, 125

fluctuations in, 126structure of, 125–126, 126fsynthesis of (glycogenesis), 125, 125f,

126–128, 127fin absorptive/fed state, 323, 326, 326finhibition by cAMP-directed pathway,

133–134primer for initiation of, 126–127regulation of, 131–134, 133f, 134f

Glycogenesis. See Glycogen, synthesis ofGlycogenin, 127, 127fGlycogenolysis. See Glycogen, degradation ofGlycogen phosphorylase, 128, 128f, 129f, 130,

134in absorptive/fed state, 322, 322factivation of, 132–133, 133fallosteric control of, 131–132, 131fAMP and, 132–133, 133fdeficiency in, 129fin fasting, 329inactive b form of, 133, 133fphosphorylation of, 63

Glycogen phosphorylase kinase, 329Glycogen storage diseases, 129–130f

type Ia (Von Gierke disease), 121, 130ftype II (Pompe disease), 129f, 131type V (McArdle syndrome), 129f

Glycogen synthase, 184in absorptive/fed state, 323active a form of, 133, 133fallosteric control of, 131–132, 131felongation of glycogen chains by, 127,

127f, 128in glycogen synthesis, 126–127, 127finactive b form of, 133, 133finhibition of glycogen synthesis and,

133–134, 134fphosphorylation of, 63

Glycolipids, 208–213. See alsoGlycosphingolipids

fatty acids in, 173fGlycolysis, 91f, 92f, 96–108

in absorptive/fed state, 100, 100f, 323,323f, 325, 325f

aerobic, 96–102, 96fenergy yield from, 104

anaerobic, 96, 96f, 102–104, 104fconcept map, 107fcontrol point and rate-limiting step of,

99–100, 100fenergy generation phase of, 101–104,

101f, 104fenergy investment phase of, 97–99, 98f,

100fenergy yield from, 104enzyme deficiencies in, 102–103during fasting, 100, 100f, 105


Index 503

gluconeogenesis favored over,reactions required for

glyconeogenesis vs., 121intermediates of, in pentose phosphate

pathwaymetabolic characteristics of, 106freactions of, 97–104regulation of, 105f

hormonal, 104–105, 105fUDP-galactose as carbon source for,

140–141, 141fGlycoprotein(s), 165–171

carbohydrates in, 165–166concept map, 171ffunctions of, 165flysosomal degradation of, 170negatively charged, low density

lipoproteins as, 232oligosaccharides of, structure of,

165–166, 166fproteoglycans vs., 165synthesis of, 166–169, 166f, 168ftransport through Golgi apparatus,

166–167, 167ftransport to lysosomes, 169, 169f

Glycoprotein storage disease, 169, 170Glycosaminoglycans (GAGs), 157–164

accumulation inmucopolysaccharidoses, 163,164f

acidic sugars in, 157f, 161, 162famino sugars in, 157f, 160, 161fcarbohydrates in, synthesis of, 162,

163fclassification of, 158concept map, 171fcore protein of, 161degradation of, 162–163, 164f

lysosomal, 163distribution of, 158, 159fextracellular or cell-surface,

phagocytosis of, 163glycoproteins vs., 165linkage region of, 158, 159f, 162monosaccharide units of, 157, 157frepeating disaccharide unit of, 157,

157fresilience of, 158, 158fstructure of, 157–158, 157f, 159f

relationship with function, 157–158sulfate groups of, addition of, 162, 163fsynthesis of, 158–162

Glycosidases, 86Glycoside bonds

between monosaccharides, 85Glycosidic bonds, 83, 84f

α(1→4), 128, 128f, 130α and β, 85carbohydrate to noncarbohydrate

structures, 85, 86fin glycogen, 126, 126f, 127f, 128

cleavage of, 128, 128f, 129fhydrolysis of, 86, 86fN-, 86, 86f

in glycoproteins, 165naming, 85O-, 86, 86f

in glycoproteins, 165in glycosaminoglycans, 158in glycosphingolipids, 209, 209f

Glycosphingolipids, 208–213acidic, 209–210, 209fantigenic, 209

as cell surface receptors, 209concept map, 217fdegradation of, 210–213

disorders of, 211–213, 211f, 212fneutral, 209, 209fstructure of, 209–210, 209fsynthesis of, 210–213, 211f

Glycosylationin collagen, 45, 46f, 47of proteins, 443f, 444

N-Glycosylation, 167Glycosyl phosphatidylinositol (GPI), 206Glycosyl residue, 86Glycosyltransferases, 85, 166–167, 167Glycochenodeoxycholic acid, 225Glycogen phosphorylase kinase

in absorptive/fed state, 322Glyoxylate, 263GM1 gangliosidosis, 212fGMP. See Guanosine monophosphate

(GMP)Golgi apparatus

apolipoprotein synthesis in, 228glycoprotein synthesis in, 166, 167f,

168fglycoprotein transport through, 166,

167fglycosaminoglycan synthesis in, 158glycosphingolipid synthesis in, 210

Gonad(s). See also Ovary(ies); Testessteroid hormone secretion from, 240

Gout, 299–301, 300f, 301f, 305fdiagnosis of, 299, 301fin Lesch-Nyhan syndrome, 296f, 297,

300primary, 299–300saturnine, 299secondary, 300–301tophaceous, 299, 301ftreatment of, 300f, 301

G0 phase, of cell cycle, 407, 407fG1 phase, of cell cycle, 406, 407fG2 phase, of cell cycle, 407, 407fG-protein coupled membrane receptor, 94f,

95, 132, 213G-proteins, 94f, 95Graft rejection, prevention of, 295f, 296Granulomatosis, chronic, 150Greek key motif, 18fGriseofulvin, 279Ground substance, 157Growth, vitamin A and, 384Growth hormone (GH), in hyperglycemia,

315f, 316GTP. See Guanosine triphosphateGTPase, 95Guanine, 291, 291f, 299, 305f, 396f

in codons/genetic code, 431, 432fdamage to and repair of, 412, 413fpairing with cytosine, 397, 397f, 398f

Guanine-7-methyltransferase, 425Guanine diphosphate-L-fucose, 166Guanine diphosphate-mannose, 166Guanine monophosphate (GMP), IMP

conversion to, 295–296, 295fGuanosine triphosphate-dependent

regulatory proteins, 95, 95fGuanosine triphosphate (GTP)

in amino acid deamination, 252in AMP synthesis, 295in protein synthesis, 437

Guanylate cyclase, 151Guanyltransferase, 425

Gynoid or pear-shaped, 350, 350f

HHaeIII restriction endonuclease, 466, 466fHaemophilus aegyptius, 466Hairpin (stem-loop) structure, 453, 453fHairpin turn, in prokaryotic gene

transcription, 421, 421fHartnup disorder, 250Haworth projection formula, 84, 85fHDL. See High-density lipoproteinsHealth, obesity and, 349, 354Heart. See also Cardiac muscle

lactate consumption in, 103Heart attack. See Myocardial infarctionHeart disease

alcohol consumption and, 364–365dietary fats and, 360–364isoenzymes and, 66, 66flipoprotein (a) in, 237plasma cholesterol and, 360–361, 361fsoy protein and, 364triacylglycerols and, 361–364

Heat shock proteins, 20Heinz bodies, 152, 152fHelix-turn-helix motif, 450, 452, 452fHeme, 25, 277

as coenzyme, for nitric oxide synthase,151

degradation of, 282–284, 282f, 283f,284f

function of, 25metabolism of, 277–278

concept map, 289fstructure of, 25, 25f, 26fsynthesis of, 278–279, 278f, 279f, 280f,

281fdefects in, 278–282, 280fend product inhibition by hemin,

278–279rate-controlling step of, 278

uroporphyrinogen conversion to, 279,279f

Heme groupof catalase, 25of cytochromes, 25, 25fof hemoglobin, 25of myoglobin, 25, 26, 26f

Heme-heme interactions, 29–30Heme oxygenase system, 282Hemeproteins, 277

globular, 25–34. See also Hemoglobin;Myoglobin

Hemin, 278–279Hemoglobin A, 27, 29–33, 33Hemoglobin A2, 33–34, 33fHemoglobin A1c, 33f, 34, 34f

in diabetes mellitus type 1, 340, 340fHemoglobin Bart’s (Hb Bart’s)

in α-thalassemia, 39, 39fin β-thalassemia, 38f, 39

Hemoglobin C disease, 36f, 37Hemoglobin F, 33fHemoglobin H disease, 39, 39fHemoglobinopathies, 35–39, 42fHemoglobin(s)

α-helix, 27carbamino, 32concept map, 41fdevelopmental changes in, 33, 33fembryonic (Hb Gower 1), 33fetal (HbF), 33

in β-thalassemia, 38–39, 38f


Index504

function of, 27, 41fgenes

β family, 34f, 35, 35fδ, 35ε, 35α family, 34, 34f, 35fγ, 35organization of, 34–35, 34fζ, 35

heme group of, 26heme-heme interactions in, 29–30high-oxygen affinity form of, 28, 28flow-oxygen affinity form of, 28, 28fminor, 33–34normal adult, 33–34, 33foxygen affinity/binding of, 27–33, 28f

allosteric effectors and, 27, 29–332,3-bisphosphoglycerate and, 31–32,

31f, 32fcarbon dioxide binding and, 32carbon monoxide binding and, 32–33,

32fcooperative, 29–30, 29fPCO2 and, 29pH and, 30, 30fPO2 and, 29, 29f, 30saturation in, 28

oxygen dissociation curve for, 29, 29f, 31sigmoidal shape of, significance of, 30

oxygen loading and unloading by, 30, 30fR form (relaxed) of, 28, 28fstructure of, 27–28, 27f, 28f, 41f

changes with deoxygenation andoxygenation, 26, 27–28, 28f

quaternary, 27–28T form (deoxy or taut) of, 28, 28f

Hemoglobin SC disease, 38Hemoglobin S disease. See Sickle cell diseaseHemolytic anemia

glycolytic enzyme deficiencies and,102–103

G6PD deficiency and, 152, 153Hemolytic jaundice, 284, 284f, 289fHemophilia A, 461Hemoproteins, 25–34, 25f. See also

Hemoglobin; MyoglobinHemosiderosis, 36Henderson-Hasselbalch equation, 6–9

application of, 7–8for bicarbonate buffer system, 9, 9fderivation of, 6for drug absorption, 9, 9ffor titration of amino acids, 7–9

Heparan sulfamidase deficiency, 164fHeparan sulfate, 159f

deficient degradation of, 163, 164fHeparin, 159fHepatic lipase, 228Hepatic porphyrias, acute, 280, 281fHepatic steatosis, 231Hepatitis

alcoholic, 318ammonia levels in, 258jaundice in, 284

Hepatocellular jaundice, 284, 289fHepatocytes, 449Hereditary coproporphyria, 280, 281fHereditary fructose intolerance (HFI), 138,

139fHereditary hyperammonemia, 258Hereditary nonpolyposis colorectal cancer

(HNPCC), 411Heterochromatin, 422, 460

Heterogeneous nuclear RNA (hnRNA), 425Heterotropic effectors, 63Hexokinase, 121

in absorptive/fed state, 326broad substrate specificity of, 98, 98fin fructose phosphorylation, 137–138, 138fglucokinase vs., 98in glucose phosphorylation, 98inhibition of, 98in mannose phosphorylation, 138

Hexokinase D, 98Hexokinase/glucokinase, 229Hexose monophosphate shunt/pathway. See

Pentose phosphate pathwayD-hexoses, in oligosaccharides, 165High altitude

2,3-bisphosphoglycerate levels and, 32, 32fsickle cell disease and, 36

High-density lipoproteins (HDLs), 234–236,321f

alcohol consumption and, 365composition of, 232fcoronary heart disease and, 360–361dietary fats and, 361–364electrophoretic mobility of, 227, 228fin esterification of cholesterol, 234–235as “good” cholesterol carrier, 236HDL2, 235, 236HDL3, 235, 236metabolism of, 234–236, 236fn-6 fatty acids and, 363obesity and, 353as reservoir for apolipoproteins, 234reverse transport of cholesterol, 235–236,

236fsize and density of, 227, 227fuptake of unesterified cholesterol by, 234,

236fVLDL transfer of triacylglycerol to,231

High fructose corn syrup 55 and 42, 365High-mannose oligosaccharides, 166, 166f,

168Histamine, 287

synthesis of, 287, 287fHistidase, 262, 263f

deficiency of, 269fHistidine, 5

α-helix disrupted by, 17catabolism of, 262, 263fdecarboxylation to histamine, 287, 287fdegradation of, 262, 263fdistal, 26, 26fin histamine synthesis, 287fin myoglobin, 26, 26fproximal, 26, 26fside chains of, 3f, 5

Histidinemia, 268f, 269fHistone acetyltransferases (HATs), 422, 422f,

455Histone deacetylases (HDACs), 422, 422fHistones, 409–410, 409f

acetylation of, 422HMG CoA. See 3-Hydroxy-3-methylglutaryl

CoA (HMG CoA)Hogness box, 423Holoenzymes, 54, 419Homocysteine, 263

conversion to cysteine, 264–265, 264f, 268fate of, 264methionine conversion to, 263, 264f

remethylation of, 264in vascular disease, 263, 265, 265f

Homocysteine-lowering therapy, 265Homocystinuria, 268f, 269f, 273, 273fHomogentisic acid, 274Homogentisic acid oxidase, 274Homologous recombination repair, 413Homotropic effectors, 62–63Homovanillic acid (HMA), 286Hormone response elements (HREs), 240,

241f, 455, 456Hormone(s)

of adipose tissue, 352–353leptin, 353, 353f

counterregulatory, 313, 316gastrointestinal, 310in glycogen regulation, 133–134, 134fin glycolysis regulation, 104–105, 105fin HMG CoA reductase regulation, 223in lipid regulation, 176, 176fplasma, 307steroid. See Steroid hormonesin triacylglycerol degradation, 190, 190f

Hormone-sensitive lipase (HSL), 190, 190fin absorptive/fed state, 322, 322f, 325in fasting, 329insulin and, 311

Housekeeping genes, 449Human genome, 465Human Genome Project, 465, 470Human immunodeficiency virus (HIV), 408

detecting exposure to, 484, 485fRNA interference and, 459

Hunter syndrome, 163, 164fHuntington disease, 433, 433fHurler syndrome, 164f, 472Hyaluronic acid, 159f, 163Hybrid duplex, in DNA replication, 402Hybridization, in situ, 472Hydantoins, 279Hydratase, 195Hydration

of fumarate, 112f, 113Hydration therapy, for sickle cell disease, 36Hydride ions, electron transport via, 76Hydrochloric acid, 248Hydrochloric acid, in protein digestion, 247Hydrogen atoms, electron transport via, 76Hydrogen bonds

in α-helix, 16amino acid, 4, 4f, 19, 19fin β-sheets, 17, 17fbetween complementary bases, 397,

397f, 398fin hemoglobin, 27–28, 28finterchain, 17intrachain, 17

Hydrogen peroxidereduction of, 148–149, 148fsuperoxide conversion to, 150

Hydrolases, 53fHydrolysis

of cAMP, 95–96, 96fin catabolic pathways, 93

Hydrophobic interactions, 19, 19fin hemoglobin, 27, 28f

Hydrophobic side chains, 4Hydrops fatalis, 39, 39fHydroxyacyl-ACP dehydratase, 186Hydroxyallysine, in collagen biosynthesis, 483-Hydroxybutyrate, 195–196, 196f, 262, 330,

330f3-Hydroxy-butyrate dehydrogenase, 19625-Hydroxycholecalciferol, 386


Index 505

25-Hydroxycholecalciferol 1-hydroxylase, 386regulation of, 386–388

5-Hydroxy-6,8,11,14 eicosatetraenoic acid (5-HPETE), 214, 215f

α-Hydroxylase, 19511-β-Hydroxylase deficiency, 238f17-α-Hydroxylase deficiency, 238f21-α-Hydroxylase deficiency, 238fHydroxylation

in collagen, 45, 45f, 46f, 47of proteins, 444, 444f

Hydroxylysine, in collagen, 45, 45f, 46f, 47Hydroxymethylbilane, 279, 279fHydroxymethylbilane synthase, 281f3-Hydroxy-3-methylglutaryl CoA (HMG CoA),

220, 220f3-Hydroxy-3-methylglutaryl CoA (HMG CoA)

reductase, 220–221, 232gene expression of, sterol-dependent,

222–223, 223finhibition of, 232phosphorylation and dephosphorylation of,

223, 223fregulation of, 222–224, 223f

3-Hydroxy-3-methylglutaryl CoA (HMG CoA)synthase

in cholesterol synthesis, 220, 220fin ketone body synthesis, 196, 196f

Hydroxymethylglutaryl CoA reductase (HMGCoA reductase), 61

Hydroxyprolinein collagen, 45, 45f, 46f, 47in elastin, 49

3-β-Hydroxysteroid dehydrogenasedeficiency, 238f

5-Hydroxytryptamine. See Serotonin5-Hydroxytryptophan, 287, 287fHydroxyurea, 36, 298hyperammonemia, 257–258, 258f

acquired, 258hereditary, 258

Hyperbilirubinemia, 284, 284fHypercalcemia, vitamin D and, 389Hypercholesterolemia, 224, 226Hyperglycemia

in diabetes mellitustype 1, 338–339, 339type 2, 344

glucose phosphorylation in, 98sorbitol and, 140

Hyperlipidemia/hyperlipoproteinemianiacin for, 380type I, 178, 229type II, 232type IIb, 380type III, familial, 231

Hyperoxaluria, primary Type 1, 253Hyperphosphatemia, 389Hypertension

diabetes mellitus and, 346obesity and, 354ftreatment of, 239

Hypertriacylglycerolemia, 229in diabetes mellitus

type 1, 339–340in type 2, 344

Hyperuricemia, 296, 299Hypervitaminosis A, 385–386Hypocalcemia, 388, 389Hypochlorous acid (HOCl), 150Hypoglycemia, 314–318, 319f

alcohol-induced, 317–318, 317fbrain damage in, 327characteristics of, 314

concept map, 319ffasting, 317glucagon and, 315, 315f, 316glucoregulatory systems in, 315f, 316insulin-induced, 316, 316fpostprandial, 316symptoms of, 314–315

adrenergic, 314neuroglycopenic, 314

in type 1 diabetes, 340–341, 341ftypes of, 316–318

Hypoglycemia unawareness, 341Hypoglycemic agents, for diabetes mellitus

type 2, 344Hypoparathyroidism, 389Hypopigmentation, in PKU, 271Hypoprothrombinemia, 390Hypoxanthine, 299Hypoxanthine-guanine

phosphoribosyltransferase (HGPRT),296, 296f, 301

Hypoxia, 2,3-bisphosphoglycerate in, 32, 32f

II-cell disease, 169Icterus. See JaundiceIduronate sulfatase deficiency, 164fL-Iduronic acid

in glycosaminoglycans, 157, 157f, 161synthesis of, 161

α-L-Iduronidase deficiency, 164fImmunoblots, 484, 485fImmunodeficiency syndromes. See also

Human immunodeficiency virus(HIV); Severe combinedimmunodeficiency disease (SCID)

DNA repair defects and, 413Immunoglobulin G (IgG), 165Immunoglobulins, production of, 461, 461fIMP. See Inosine monophosphateInborn errors of metabolism, 270–274Incretins, 310Indomethacin, 214, 301Infarction, in sickle cell disease, 36, 37fInflammatory processes, in gout, 299Influenza, nutrition and, 361fInitiation codons, 438f, 439Initiator tRNA, 438f, 439Inner membrane particles, 74iNOS, 151Inosine, for boosting 2,3-BPG levels in blood,

32Inosine monophosphate dehydrogenase, 295fInosine monophosphate (IMP)

conversion to AMP and GMP, 295–296,295f

as parent purine nucleotide, 293in purine synthesis, 293–296, 294fsynthesis of, 293

Inositol 1,4,5-triphosphate (IP3), in signaltransmission, 205–206, 205f

Inositol triphosphate (ITP), in intracellularsignaling, 205, 205f

Insig protein, 223In situ hybridization, 472Insulin, 307–313, 353

in absorptive/fed state, 328fin acetyl CoA carboxylase regulation, 184,

184fanabolic effects of, 308carbohydrate metabolism and, 311concept map, 319fdeficiency of

absolute, in type 1 diabetes mellitus,

336, 336frelative, in type 2 diabetes mellitus,

341degradation of, 308epinephrine and, 310, 310f, 319fexogenous. See Insulin therapyfructose 2,6-bisphosphate and, 100, 100fglucagon opposing action of, 314, 319fglucagon secretion and, 309, 313glucokinase and, 310, 313glycerol phosphate synthesis and, 189glycogen degradation and, 133glycolysis and, 105, 105fin HMG CoA reductase regulation, 223hormone-sensitive lipase and, 190in hypoglycemia, 314–318, 315fhypoglycemia and

alcohol consumption and, 318in integration of metabolism, 307lipid metabolism and, 311mechanism of action, 311–313, 311fmembrane effects of, 312, 312fmetabolic effects of, 311phosphofructokinase and, 313protein synthesis and, 311secretion of

amino acids and, 310by β cells, 310, 310fcoordination with glucagon secretion

and, 309, 314gastrointestinal hormones and, 310glucose levels and, 310, 310finhibition of, 310during onset of type 1 diabetes

mellitus, 338, 338fregulation of, 309–310, 310f, 313stimulation of, 309–310

in signal transduction, 311f, 312structure of, 308, 308fsynthesis of, 308, 308ftime course of actions, 313triacylglycerol degradation and, 189, 190f

Insulinase, 308Insulin-dependent glucose transport (GLUT-4)

proteins, 331Insulin-induced hypoglycemia, 316, 316fInsulin receptor, 311–312, 311fInsulin receptor substrate (IRS) proteins, 311f,

312Insulin resistance

causes of, 343obesity and, 342in type 2 diabetes mellitus, 342–343, 343f

Insulin resistance syndrome, 353Insulin-sensitive glucose transporters (GLUT-

4), 312Insulin therapy

hypoglycemia induced by, 316, 316f,340–341, 340f

for type 1 diabetes mellitus, 340, 340fstandard vs. intensive, 340, 340f

for type 2 diabetes mellitus, 344Insulitis, 338Intercellular communication, 94, 94fIntermediate-density lipoproteins (IDLs), 231International Union of Biochemistry and

Molecular Biology (IUBMB), enzymenomenclature of, 53, 53f

Intestinal mucosal cellschylomicron assembly in, 177f, 228, 229fenzymes synthesized by, carbohydrate

digestion by, 86–87, 87flipid absorption by, 176, 177flipid secretion by, 177f, 178


Index506

monosaccharide absorption by, 87Intestine(s)

bacterial action in, ammonia from, 257cholesterol synthesis in, 220small

dietary lipid processing in, 175dietary nucleic acid degradation in,

298, 299foligopeptide digestion in, 249

urobilins formation in, 283–284vitamin D and, 388

Intracellular communication, 94, 94f,205–206, 205f

Intrinsic factor, 377Introns, removal of, 426–427, 427fIodine, Dietary Reference Intakes for, 358fIonic interactions

of amino acids, 19, 19fof hemoglobin, 27–28, 28f

IronDietary Reference Intakes for, 358fin heme, 25, 25fmetabolism of, 458–459, 458fin porphyrins, 277

Iron-deficiency anemia, 374, 374fIron-regulatory proteins (IRPs), 458–459,

458fIron responsive elements (IREs), 458, 458fIron-sulfur center, of NADH dehydrogenase,

75, 75fIslets of Langerhans, 307, 308f, 313, 316Isocitrate

citrate isomerization to, 111f, 112oxidation and decarboxylation of, 111f,

112Isocitrate dehydrogenase, 112, 114, 114f,

183Isoelectric form, of amino acid, 7, 7fIsoelectric point, for amino acids, 8–9Isoenzymes, 65–66, 65f

heart disease and, 66, 66fquaternary structure of, 65–66

Isoforms, 21, 231, 457fIsoleucine

in absorptive/fed state, 324α-helix disrupted by, 17catabolism of, 266–267, 266fformation of succinyl CoA and, 265, 266hydrophobic interactions and, 19ffor maple syrup urine disease, 273side chains of, 2f

Isomaltase, 87Isomaltase-sucrase deficiency, 88Isomerases, 53fIsomerization

of citrate, 111f, 112of dihydroxyacetone phosphate, 101of glucose-6-phosphate, 99, 99f

Isomers, 83–84, 84fIsoniazid, 377f, 378Isopentenyl pyrophosphate (IPP), 221Isoprenoids, 221Isotretinoin, 385, 385f, 386Isovaleryl Co A dehydrogenase deficiency,

266Isozymes, 21, 213ITP. See Inositol triphosphate

JJaundice, 284–285, 284f, 285f

bilirubin concentration in, determinationof, 285

hemolytic, 284, 284f, 289fhepatocellular, 284, 289fneonatal, 284f, 285, 285f, 289f

phototherapy for, 285, 285fobstructive, 284–285, 289ftypes of, 284–285

Joule, 359

KKaryotyping, 476Keratan sulfates, 158, 159f, 162–163Keratins, 16, 382α-Keto acid dehydrogenase, 147Ketoacidosis alcoholic, 318ketoacidosis alcoholic, 318Ketoacidosis, type 1 diabetes and, 338–339α-Ketoacid(s), 118

in amino acid catabolism, 245as gluconeogenic precursors, 117–118as product of oxidative deamination,

252–253as product of transamination, 250–252synthesis of nonessential amino acids

from, 267–268, 268f3-Ketoacyl-ACP reductase, 1863-Ketoacyl-ACP synthase, 184β-Ketoacyl-CoA thiolase, 192fα–Ketobutyrate, 265Ketogenesis, 196, 196f, 197f

in fasting, 330–331Ketogenic amino acids, 262, 262f, 266α-Ketoglutarate

in fasting, 332formation of

in amino acid catabolism, 250–252,250f, 252f

from amino acids, 262in gluconeogenesis, 118oxidative decarboxylation of, 112, 112f

thiamine and, 379, 379fin tricarboxylic acid cycle, 111f, 112, 112f

α-Ketoglutarate dehydrogenase complex,111–112, 111f, 114, 114f, 147, 266

thiamine pyrophosphate as coenzyme for,378f, 379, 379f

Ketohexokinase. See FructokinaseKetolysis, 196–197Ketone bodies, 118, 195–197

cerebral use of, 195, 327, 332, 332fexcessive production, in diabetes mellitus,

197, 339in fasting, 330–331, 330fglucagon and, 314synthesis by liver, 196, 196f, 197fuse by peripheral tissue, 196–197, 197f

Ketonemia, 197Ketonuria, 197Ketoses, 83, 83fKetosis

in type 2 diabetes, 344in type 2 diabetes mellitus, 339

Kidney(s)cytochrome P450 monooxygenase system

of, 149fructose metabolism in, 138gluconeogenesis in, 117in long-term fasting, 332

Kidney stones, 250Knock-in mice, 485Knockout mice, 486Krabbe disease, 212fKrebs cycle. See Tricarboxylic acid (TCA)

cycleKwashiorkor, 369, 369fKyphotic, 49

Llac genes

lacA, 451f, 452lacI, 451f, 452lacY, 451f, 452lacZ, 451f, 452

α-Lactalbumin, 142β-Lactam antibiotics, 62Lactase, 87, 88, 140, 141Lactate, 96

consumption of, 103in Cori cycle, 118, 118fformation in muscle, 103in gluconeogenesis, 118pyruvate reduction to (anaerobic

glycolysis), 103–104, 104fLactate dehydrogenase, 103, 111Lacteals, 178Lactic acidosis, 104

congenital, 111Lactose, 85, 140, 365

in regulation of gene expression, 451f,452

synthesis of, 142, 142fLactose intolerance, 88, 88fLactose operon, 450–452, 451fLactose synthase, 142Lactosylceramide, 209Lagging strand, 402, 403fLanosterol, 221Laparoscopic cholecystectomy, 226L-configuration, of amino acids, 5, 5fLDH. See Lactate dehydrogenaseLDL. See Low-density lipoproteinsL-dopa (levodopa), 286Lead, noncompetitive inhibition of enzymes

by, 61–62Leading strand, 402, 403fLead poisoning, 279, 281f, 374fLeber hereditary optic neuropathy, 80Lecithin. See PhosphatidylcholineLeigh syndrome, 111Leishmania, 206Leptin

in diabetes mellitus, 343in obesity, 352–353, 352f, 353f

Lesch-Nyhan syndrome, 296–297, 296f, 297fLeucine, 19f

in absorptive/fed state, 324catabolism of, 262, 266–267, 266fdegradation of, 266, 266ffor maple syrup urine disease, 273side chains of, 2f

Leucine zipper, 423, 450, 457Leukemia, 262Leukodystrophy

globoid cell, 212fmetachromatic, 212f

Leukotriene(s), 213–214LTA4, 213f, 215fLTB4, 215fLTC4, 215fsynthesis of, 214, 215f

Ligandin, 282Ligases. See also specific ligases

classification of, 53fLignoceric acid, 182f, 207Limit dextrin, 128, 129fLineweaver-Burk plot, 59, 59f, 60, 60f, 61fLingual lipase, 173, 174α-1,4 linkages, 126, 126f, 127, 128α-1,6 linkages, 126fLinker DNA, 410, 410fLink proteins, in proteoglycan aggregates,

158, 160fLinoleic acid, 182f, 213, 214f, 363


Index 507

α-Linoleic acid, 182, 182fα-Linolenic acid, 363Lipid(s)

complex. See also Glycosphingolipids;Phospholipids

metabolism of, 201–218dietary

absorption by intestinal mucosalcells, 176, 177f

concept map, 180fcoronary heart disease and,

361–364degradation by pancreatic enzymes,

174f, 175–176digestion of, 173–178, 174femulsification in small intestine, 175hormonal regulation of, 176, 176fmalabsorption of, 177, 178fmetabolism of, 173–180, 180fin neonates, 174processing in stomach, 173–174use by tissues, 178

in fasting, 332, 332ffunctions of, 173glucagon and, 314insulin and, 31143fplasma levels of, dietary fats and,

361–362, 361fsecretion from enterocytes, 177–178,

177fstructure of, 173, 173f

Lipid storage disease, 211Lipoic acid

in arsenic poisoning, 111as coenzyme


for α-ketoglutarate dehydrogenasecomplex, 112

for pyruvate dehydrogenasecomplex, 110

Lipoprotein(a), in heart disease, 237Lipoprotein lipase, 178, 228–230, 311

in absorptive/fed state, 325, 326activation of, 231deficiency of, 178, 228–229degradation of triacylglycerol by,

228–229in diabetes mellitus

type 1, 339–340type 2, 344

in fasting, 331insulin and, 311regulation of, 229–230

Lipoprotein(s)cholesterol in, 227, 228fcomposition of, 227, 231, 232fconcept map, 243felectrophoretic mobility of, 227, 228fin heart disease, 237high density. See High-density

lipoproteins (HDLs)intermediate density (IDL), 231low density. See Low-density

lipoproteins (LDLs)plasma, 227–237size and density of, 227, 227fvery low density. See Very-low-density

lipoproteins (VLDLs)Lipoxins, 214Lipoxygenase, 214

5-Lipoxygenase, 214Lisinopril, 62Liver

in absorptive/fed state, 322–324, 323famino acid metabolism in, 323f, 324carbohydrate metabolism in,

322–324, 323ffat metabolism in, 323f, 324intertissue relationships of, 328f

ammonia transport to, 253bile acid synthesis in, 149, 224bilirubin uptake by, 282, 283fcholesterol synthesis in, 220chylomicron remnants in, 178, 230communication with other metabolic

organs, 207, 207fcytochrome P450 monooxygenase

system of, 149D-amino acids metabolized by, 253detoxification in, 149in diabetes mellitus

type 1, 333, 339ftype 2, 342, 344, 345f

in energy metabolism, 307, 307fin fasting, 329–331, 330f

carbohydrate metabolism in,329–330, 330f

fat metabolism in, 330–331, 330fintertissue relationships of, 334f

fatty, 231fatty acid synthesis in, 183, 324fructose metabolism in, 138gluconeogenesis in, 117glycogen in, 125–126, 126f, 131, 135fheme degradation in, 282, 282fheme synthesis in, 278lactate consumption in, 103vitamin A transport/release to, 382,

383fLiver disease

aminotransferases in, 65, 251–252,251f

ammonia levels in, 257–258Liver parenchymal cells, glucose

phosphorylation in, 98L-Methylmalonyl CoA, 194Long-chain fatty acids (LCFA), 181

transport into mitochondria, 190–192,191f

Long-chain fatty acyl CoA synthetase(thiokinase), 190

Lovastatin, 224Low-density lipoproteins (LDLs), 227, 227f,

231–234, 232fchemically modified, uptake by

macrophage scavengerreceptors, 234, 235f

composition of, 231, 232fcoronary heart disease and, 360–361dietary cholesterol intake and, 364,

364felectrophoretic mobility of, 227, 228fendocytosis of, 232, 233ffunctional receptors for, deficiency of,

232metabolism of, 230f, 231–234, 233fas negatively charged glycoproteins,

232n-6 fatty acids and, 363niacin and, 380oxidation of, 234, 235fsize and density of, 227, 227f

VLDL conversion to, in plasma, 231Lower body obesity, 350, 350fLow-fat diet, 362fLungs, α1-antitrypsin in, 50, 50fLung surfactant

phosphatidylcholine in, 204in respiratory distress syndrome, 204

Luteinizing hormone (LH), 239f, 240Lyases, 53fLynch syndrome, 411Lysine, 266

α-helix disrupted by, 17as carnitine source, 191catabolism of, 262in collagen, 47, 48, 48f

hydroxylation of, 45, 45f, 46f, 47in elastin, 49in hemoglobin C disease, 37in histones, 410ionic bonds and, 19fside chains of, 3f, 5transport of, 250

Lysophosphatidic acid, 189fLysophosphatidyl choline, 175, 234Lysophosphoglyceride, 207Lysophospholipase, 176Lysophospholipid, 175Lysosomal degradation, of

glycosaminoglycans, 163Lysosomal enzymes, 247Lysosome(s), 54f

in degradationof chylomicron remnants, 230of glycogen, 130–131of glycophospholipids, 210of glycoproteins, 170of glycosaminoglycans, 162–163, 164fof proteins, 246–247

glycoprotein transport to, 169, 169fLysyl hydroxylase

deficiency of, and Ehlers-Danlossyndrome, 48

hydroxylation in collagen by, 47Lysyl oxidase

in collagen biosynthesis, 48, 48ftropoelastin polypeptides deaminated by,

49

MMacrocytic anemia, 374, 374fMacronutrients, 357


caloric consumption and distribution ofcalories, 365, 365f

concept map, 370fMacrophages, nitric oxide and, 151Macrophage scavenger receptors, uptake of

chemically modified LDL by, 234Mad cow disease, 22Magnesium, Dietary Reference Intakes, 358fMalaria, resistance to

G6PD deficiency and, 152sickle cell trait and, 37, 38f

Malateformation from α-ketoglutarate, 112fformation of oxaloacetate from, 113, 113ffumarate hydration to, 112f, 113in gluconeogenesis, 119, 119foxaloacetate reduction to, 119, 119foxidation of, 113, 113fin urea cycle, 254f, 255

Malate-aspartate shuttle, 79f, 80Malate dehydrogenase, 113, 119


Index508

Malic enzyme. See NADP+-dependentmalate dehydrogenase

Malnutrition, protein-calorie, 369Malonyl CoA

carboxylation of acetyl CoA to, 183–184,184f

carnitine shuttle inhibited by, 191, 191fMalonyl CoA-ACP-transacylase, 184Maltase, 87Maltose, 85, 365Mammary glands, lactating, fatty acid

synthesis in, 183Manganese, Dietary Reference Intakes for,

358fMannose

conversion to fructose 6-phosphate, 138epimers, 83, 84as isomer, 83, 84f

Mannose 6-phosphate, 138α-Mannosidosis type 1, 170Maple syrup urine disease (MSUD), 266,

268f, 269f, 272–273classification of, 272–273screening and diagnosis of, 273treatment of, 273

Marasmus, 369Marfan’s syndrome, 49Maternal PKU syndrome, 272Maturity onset diabetes of the young

(MODY), 99Maximal velocity (Vmax)

allosteric effectors and, 62–63, 62fof enzyme-catalyzed reactions, 57, 57f

competitive inhibition and, 60, 60fnoncompetitive inhibition and, 61, 61f

McArdle syndrome, 129fMediterranean diet, 362, 362fMedium-chain fatty acids, 192Medium-chain fatty acyl CoA dehydrogenase

(MCAD) deficiency, 193Megaloblastic anemia, 267, 374, 375, 393fMelanin, 288

in albinism, 273in phenylketonuria, 271

Melanocytes, 288α-Melanocyte stimulating hormone (α−MSH),

353Melatonin, 287Melting temperatures

of DNA, 398, 398fof fatty acids, 182

Membrane protein anchoring, 206, 206fMembrane transport systems, 79–80Menadione, 389Menaquinone (vitamin K2), 389Menkes disease, 48Mental retardation, in phenylketonuria, 271,

271fMessenger RNA (mRNA)

alternative splicing patterns of, 427, 428fcoding for protein synthesis, 435codons of, 431–432, 432f

mutations of, 432f, 433–434, 433f,434f

recognition by tRNA, 437, 437fediting, 457–458, 457feukaryotic, 418, 419f, 425–427, 426f

posttranscriptional modification of,425–427, 426f, 454, 457–460

exons, splicing of, 426–427, 427fframe-shift mutation of, 434, 434fintrons of, 426

removal of, 426–427, 427f

levels of, determination of, 483–484, 484fmissense mutation of, 432f, 433monocistronic, 438nonsense mutation of, 432f, 433polycistronic, 438, 450regulatory ribosomal protein and, 454,

454fsilent mutation of, 432f, 433splice site mutation of, 427stability of, 458–460, 458f, 460ftranscription of, 450translation of, 431–443, 431f, 460, 460f

components required for, 434–437initiation of, 438–439, 440fsteps in, 438–442, 440–441f

trinucleotide repeat expansion of, 433,433f

Metabolic acidosis, 195Metabolic map, 91, 92fMetabolic rate, resting (RMR), 359, 359fMetabolic syndrome, 353Metabolism, 73f, 91–93, 92f

defined, 91four major organs in, 307

communication between, 307, 307finborn errors in, 268–274integration of, 307

concept map, 319fregulation of, 93–96

by adenylyl cyclase cascade, 94–96,95f

by intercellular signals, 94by intracellular signals, 94by second messenger systems, 94

tricarboxylic acid cycle in, 109Metachromatic leukodystrophy, 212fMetal ions, as cofactors, 54Metalloporphyrins, 277. See also

Porphyrin(s)Metformin, 344Methane, 267Methanol, 267Methemoglobinemias, 38Methemoglobin (Hb M), 38Methionine

as carnitine source, 191catabolism of, 263–265, 264fresynthesis of, 264, 264fside chains of, 2fsynthesis of, 375, 375f

Methotrexatedihydrofolate reductase inhibited by, 304,

375folic acid absorption and, 375purine synthesis inhibited by, 293, 294f,

304, 304fMethylation, of S-adenosylmethionine, 460,

461Methylcobalamin, 264, 264f, 375, 376fMethyl-directed mismatch repair, 411, 411fN5-N10-Methylene, 376N5,N10-Methylenetetrahydrofolate, 263, 263fMethyl group, activated in SAM, 2643-Methylcrotonyl CoA carboxylase, 2667-Methylguanosine cap, 426, 426fMethylmalonic acidemia, 194, 377Methylmalonic aciduria, 194, 377D-Methylmalonyl CoA, 194Methylmalonyl CoA mutase, 194

deficiency of, 268f, 269fMethylmalonyl CoA racemase, 194Mevalonic acid (mevalonate), 220–221, 221f,

222fMice, knockout, 486

Michaelis constant (Km), 59, 59fallosteric effectors and, 62f, 63apparent, competitive inhibition and, 60,

60fnoncompetitive inhibition and, 61, 61f

Michaelis-Menten equation, 58–59Microarrays, DNA, 483–484, 484f, 485fMicrocytic anemia, 374, 374fMicronutrients, 357. See also Vitamin(s)MicroRNA (miRNA), 459Microsatellite DNA, 475Microsomal cytochrome P450

monooxygenase system, 279Microsomal TAG transfer protein (MTP),

177–178, 228Mineralocorticoids, 237Missense mutation, 432f, 433Mitchell hypothesis, 77–79Mitochondrial DNA, 80

long-chain fatty acid transport to, 190–192,191f

mutations in, 80short- and medium-chain fatty acid

transport into, 192Mitochondrial entry sequence, 443Mitochondrial myopathies, 80, 80fMitochondrial RNA polymerase, 424Mitochondrion, 54f, 74

apoptosis and, 80cristae of, 74cytochrome P450 monooxygenase system

of, 149fatty acid oxidation in, 190–192, 191finner membrane of

ATP synthesis in, 74, 74fcardiolipin in, 202electron transport chain in, 74transport systems of, 79–80, 79f

matrix of, 74, 74fporphyrin synthesis in, 278structure of, 74, 74f

Mixed micelles, 176, 177, 177fMolecular biology, central dogma of, 395, 395fMolybdenum, Dietary Reference Intakes for,

358f2-Monoacylglycerol, 174f, 175–176Monoacylglycerolacyltransferase, 176, 177fMonoamine oxidase inhibitors, 286–287Monoamine oxidase (MAO), catecholamine

metabolism and, 286, 286fMonocistronic mRNA, 438Monocytes, 150Monooxygenases (mixed function oxidases),

149Monosaccharide(s), 83–85, 83f, 365

absorption by intestinal mucosal cells, 87anomeric forms of, 84, 85fceramide, 209classification of, 83, 83fconcept map, 89fcyclization of, 84–85dietary, 143fexamples of, 83, 83fglycosidic bonds between, 83, 84fjoining of, 85metabolism of, 137–144

concept map, 143fmutarotation of, 84, 85f

Monounsaturated fat, 361–362, 362f, 364fMortality, obesity and, 354, 354fMotifs, 18, 18f, 19Moxalactam, 390MstII restriction endonuclease, 477, 478fMucin, 165, 165f


Index 509

Mucopolysaccharides, 157. See alsoGlycosaminoglycans

Mucopolysaccharidoses, 163, 164fMultiple carboxylase deficiency, 381Muscle(s)

cardiaccarnitine deficiency in, 192lipoprotein lipase in, 228myoglobin in, 26skeletal vs., 326


in diabetes mellitustype 1, 338, 339ftype 2, 342, 344

metabolic role of, 307, 307fskeletal

calcium and, 131–132, 132fcardiac vs., 326carnitine deficiency in, 192contraction of, 131exercising, glycogen as fuel source for,

332glycogen in, 125–126, 126f, 131–132,

131f, 133flactate formation in, 103, 118lipoprotein lipase in, 228myoglobin in, 26resting, 331–332, 332f

in absorptive/fed state, 325–326,326f

in fasting, 331–332, 332ffatty acids as fuel source for, 332oxygen consumption of, 326

smooth, nitric oxide and relaxation of,150–151, 151f

Muscular dystrophy, 486Mutarotation, 84, 85fMutations, 411, 475

detection of, using Southern blotting, 473frame-shift, 434, 434fmissense, 432f, 433nonsense, 432f, 433silent, 432f, 433splice site, 427, 434trinucleotide repeat expansion, 433, 433f

Mut proteins, 411Mycophenolic acid (MPA), 295f, 296Myeloperoxidase (MPO) system, 150Myocardial infarction, enzyme markers of, 65f,

66, 66f, 287Myoglobin, 16

α-helical content of, 26, 26ffunction of, 26heme group of, 25, 26, 26foxygen affinity/binding of, 28–29oxygen dissociation curve for, 28–29, 29fpolar and nonpolar amino acid residues in,

26structure of, 26, 26f

Myophosphorylase, deficiency in, 129fMyosin light-chain kinase, 151Myotonic dystrophy, 433, 433fMyristic acid, 361

NN-acetylneuraminic acid (NANA), 166

in acidic glycosphingolipids, 209synthesis of, 160

NAD. See Nicotinamide adenine dinucleotideNADH, 73

in alcohol-induced hypoglycemia, 317,317f

in conversion of pyruvate to lactate(anaerobic glycolysis), 97,103–104, 103f

formation ofin electron transport chain, 75in fatty acid oxidation, 192, 193fin glycolysis, 101

oxidation of, 76, 77ftransport of, to inner mitochondrial

membrane, 79–80, 79fin tricarboxylic acid cycle, 111, 111f

NADH-cytochrome b5 reductase (NADH-methemoglobin reductase), 38

NADH dehydrogenase, 75, 75fNADH-dependent malate dehydrogenase,

186NADP+-dependent malate dehydrogenase,

152, 186NADPH

in cholesterol synthesis, 220–221, 221fcompetitive inhibition of G6PD by,

145–146concept map, 155fin cytochrome P450 monooxygenase

system, 149–150, 149fin fatty acid synthesis, 186, 186fG6PD deficiency and, 152in nitric oxide synthesis, 150–151, 151fin pentose phosphate pathway,

145–146in phagocytosis, 150, 150fproduction of, in pentose phosphate

pathway, 145–146, 146fin reduction of hydrogen peroxide,

148–149, 148fin reductive biosynthesis, 147in sphingomyelin synthesis, 206, 207fin steroid hormone synthesis, 237, 238fstructure of, 147fuses of, 147–151

NADPH-dependent 2,4-dienoyl CoAreductase, 195

NADPH oxidase, 150deficiencies in, 150

Native conformation, of protein, 23fNatural killer (NK) cells, 301Negative regulation, of gene expression,

453Neomycin, 255Neonate(s)

jaundice in, 284, 285, 285f, 289fG6PD deficiency and, 153phototherapy for, 285, 285f

PKU screening in, 270, 271premature, vitamin E deficiency in, 391vitamin K deficiency in, 390

Nephropathy, 345Nervonic acid, 182f, 207Network-forming collagen, 44, 44fNeural tube defects, 265, 375, 393f, 476Neuraminic acid, in oligosaccharides, 165Neurocan, 158Neurodegeneration, in Niemann-Pick

disease, 208Neurofibrillary tangles, in Alzheimer

disease, 21Neuroglycopenia, 315Neuropathy, diabetic, 345Neuropeptide Y (NPY), 353Neurotransmitter(s)

in metabolic regulation, 94, 94f, 95nitric oxide as, 150–151, 151f

Neutral fat, 188

Neutral fecal sterols, 224Neutrophils, 150Niacin, 54, 379–380, 392–393f

active forms of, 379, 379f, 392fclinical indications for, 380deficiency of, 380, 393f

three Ds of, 380dietary intake of, 380

Dietary Reference Intakes for, 358fsources of, 380

distribution of, 380function of, 380–381for hyperlipidemia, 380structure of, 379f, 380

Nickel, Dietary Reference Intakes for, 358fNicotinamide adenine dinucleotide (NAD+),

73, 75, 379–380, 379f, 392fas coenzyme, 54


for α-ketoglutarate dehydrogenasecomplex, 112, 112f

for pyruvate dehydrogenasecomplex, 110, 111f

in conversion of pyruvate to lactate(anaerobic glycolysis), 103,103f

in mitochondrial matrix, 74NADPH vs., 147oxidation of NADH to, 76, 77freduced form of, 380, 380f. See also

NADP+

structure of, 379fin tricarboxylic acid cycle, 113, 113f

Nicotinamide adenine dinucleotidephosphate (NADP+)

reduced form of, 380, 380fstructure of, 379f

Nicotinic acid. See NiacinNiemann-Pick disease, 208, 208f, 211,

212f, 232Night blindness, 384, 393fNinhydrin, 15Nitric oxide (NO)

actions on vascular endothelium, 151macrophage bactericidal activity and,

151, 151fas neurotransmitter, 151, 151fplatelet aggregation inhibited by, 151synthesis of, 150–151, 151f

Nitric oxide synthase, 150–151, 151fendothelial (eNOS), 151inducible (iNOS), 151neural (nNOS), 151

Nitrogenin dietary protein, 245, 247–249disposal of, 245–260

as ammonia, 256–258in protein digestion, 247–249in urea cycle, 245f, 253–256, 253f,

254f, 255fmetabolism of, 245–247

concept map, 259fremoval from amino acids, 245,

250–253, 259fNitrogen balance, 368Nitrogen-containing bases, in nucleotides,

291–292, 291fNitrogen-containing compounds, amino

acids as precursors of, 277, 277fNitroglycerin, 151Nitroprusside, 151


Index510

Nitrous acid, 412Nitrous oxide (N2O), 151N-linked glycoproteins, 142N-linked glycosides, synthesis of, 167–169,

168fN-linked oligosaccharides, 165, 166

final processing of, 168, 169fnNOS, 151Non-coding RNA (ncRNA), 417Noncompetitive inhibition, of enzymes, 61–62,

61f, 62fexamples of, 61–62Lineweaver-Burke plot, 61, 61f

Nonessential amino acids, 261, 262fbiosynthesis of, 267–269

Nonhomologous end-joining repair, 413Nonpolar amino acids, 2–4, 2f, 4f

hydrophobic interactions of, 2, 19, 19flocation in proteins, 2, 4, 4fin myoglobin, 26

Nonsense codons, 432Nonsense mutation, 432f, 433Nonshivering thermogenesis, 79Non-spherocytic hemolytic anemia,103, 153Norepinephrine

catecholamine synthesis and, 285–286,286f

in energy metabolism, 307in fasting, 331functions of, 285methyl group and, 264

Normocytic anemia, 374fNorthern blot, 473, 483, 485fNO synthase, 151NPY, 353N-terminal amino acid, 247N-terminal residue

in protein degradation, 247Nuclear localization signal, 443Nuclear receptor superfamily, 456Nucleic acids, 292. See also DNA; RNA

detection of low-abundance sequences,482

dietary, degradation of, 298, 299ftypes of, 395

Nucleofilament, 411Nucleoid, 398Nucleolus, RNA synthesis in, 422Nucleoplasm, in RNA synthesis, 422Nucleoprotein, 396Nucleoside analogs, inhibition of DNA

synthesis by, 408–409, 409fNucleoside diphosphate kinase, 112, 127, 296,

296fNucleoside diphosphate (NDP), 292

nucleoside monophosphate conversion to,296, 296f

Nucleoside monophosphate kinases, 296, 296fNucleoside monophosphate (NMP), 292

conversion to nucleoside diphosphates andtriphosphates, 296, 296f

Nucleoside 5’-phosphate, 292Nucleoside(s), 292. See also Nucleotide(s)Nucleoside triphosphate (NTP), 292

nucleoside monophosphate conversion to,296, 296f

Nucleosomes, 422fate during DNA replication, 411formation of, 409–410, 410f

5’-Nucleotidase, 2995’-Nucleotide, 292Nucleotide excision repair, 411, 411fNucleotide(s), 292

function of, 291

high-energy bond of, 292, 293fmetabolism of, 291–306

concept map, 305fpentoses added to, 292, 292fpurine

degradation of, 298–302, 300f, 305fparent, inosine monophosphates as,

293purine base conversion to, 296, 296fsalvage pathway for, 296–297, 296fstructure of, 291–292, 291f, 292fsynthesis of, 292–297, 305f

committed step of, 293, 294fdrugs targeting, 293, 294f, 305f

pyrimidinedegradation of, 304formation of, 302–303, 303fsalvage of, 304structure of, 291–292, 291f, 292fsynthesis of, 302–304, 303f, 305f

structure of, 291–292, 291f, 292fsynthesis of, 291unusual bases of, 291–292, 292f

Nucleotide sequences, 396, 396falteration of, consequences of, 432f,

433–434mapping of, 449. See also DNA analysis

Nucleotidyltransferase, 425Nutrients, 357

Acceptable Macronutrient DistributionRanges in, 360, 360f

availability of, and metabolism, 94classes of, 357, 357fhepatic distribution of, 322–324

Nutrition, 357–372cancer and, 360, 361fDietary Reference Intakes in, 357–358,

357f, 358finfluence on common causes of death,

361fmacronutrients in, 360, 360f

concept map, 370fvitamins in, 372–394

Nutritional anemias, 374, 374fNutritional rickets, 388Nutrition Facts labels, 364

OObesity, 349–356

adipose tissue in, 350–353, 353fafferent signaling molecules in, 353, 353fassessment of, 349–350body mass index in, 349, 349f, 353f, 354fcarbohydrate intake and, 365cause of, 351–352childhood, 349concept map, 355fdiabetes mellitus and, 349, 354diseases associated with, relative risk of

developing, 349, 354environmental and behavioral factors in,

352epidemic in United States, 349fat deposition in


fats cells in, 351, 351fgenetic factors in, 352health and, 354insulin resistance and, 342, 342f, 346f,

353lower body, 350, 350fmetabolic changes in, 353molecules influencing, 352–353

mortality and, 354, 354fpharmacotherapy for, 355surgical treatment of, 355upper body, 350, 350fweight reduction in, 354–355

Obstructive jaundice, 284–285, 289fOculocutaneous albinism, 272, 272fO-glycosides, 86, 86fO-glycosidic bonds, 86, 86f

in glycoproteins, 165in glycosaminoglycans, 158in glycosphingolipids, 209, 209f

Oils, 188Okazaki fragments, 403, 407Oleic acid, 182fOligo-α(1→4)→α(1→4)-glucan transferase,

130Oligomycin, 78Oligonucleotide probes

in sickle cell disease, 472, 472f, 473fsynthetic, 471–472, 472f

Oligonucleotide(s), 298Oligopeptides, digestion of, 249Oligosaccharide(s), 83, 85

carbohydrate-protein linkage in, 165ceramide, 209complex, 166, 166fdolichol-linked, 167

synthesis of, 167, 168fin glycoproteins, structure of, 165–166,

166fhigh-mannose, 166, 166fN-linked, 165, 166

synthesis of, 167–169, 168fO-linked, 165

synthesis of, 166–167Oligosaccharidoses, 169, 170O-linked glycosides, synthesis of, 166–167O-linked oligosaccharides, 165, 166–167Omega-6 fatty acids, 363Omega (ω) oxidation fatty acids, 195One-carbon units, 267

folic acid as carrier of, 267Operators, in prokaryotic transcription, 450Operons

bacterial, 450lactose, 450–452, 451ftryptophan, 452–453, 453f

Opsin, 383f, 384Optical isomers, 5, 5fOptical properties of amino acids, 5, 5fOral tolerance tests, for digestive enzyme

deficiencies, 88Organic molecules, as enzyme cofactors, 54Origin of replication, 399, 400fOrlistat, 175Ornithine

formation from arginine, 262transport of, 250in urea cycle, 255, 255f

Ornithine transcarbamoylase, 254fOrnithine transcarbamoylase deficiency, 258Orotate phosphoribosyltransferase, 302Orotic acid, synthesis of, 302, 303fOrotic aciduria, 303, 303f, 304Orotidine 5’-monophosphate (OMP), 302Orotidylate decarboxylase, 302Osmotic diarrhea, 87Osteoblasts, 45Osteocalcin vitamin K, 390Osteogenesis imperfecta (OI), 49, 49f, 51f

type II (osteogenesis imperfectacongenita), 49

type I (osteogenesis imperfecta tarda), 49


Index 511

Osteomalacia, 388, 389f, 393fOvary(ies), hormonal secretion by, 237, 240,

240fOverweight, classification of, 349Oxaloacetate (OAA)

carboxylation of pyruvate to, 105, 106f,118–119, 119f

NADPH production in, 183, 183fin citrate synthesis, 111–112, 111fcytosolic, decarboxylation of, 119f, 120formation of

in amino acid catabolism, 251fin gluconeogenesis, 118–120, 119fmalate oxidation to, 113reduction to malate, 119, 119ftransport to cytosol, 119, 119fin tricarboxylic acid cycle, 109, 109f,

111–112Oxidant drugs, 153Oxidation

of arachidonic acid, 213, 214fof fatty acids, 189–195of glyceraldehyde 3-phosphate, 101, 101fof isocitrate, 112of LDL, 234, 235fof malate, 113of palmitoyl CoA, 192, 193fof succinate, 112f, 113

Oxidative deaminationallosteric regulation of, 252of amino acids, 245, 252–253, 252fcoenzymes in, 252, 252fdirection of reactions, 252

Oxidative decarboxylationof α-ketoglutarate, 112, 112f

thiamine and, 379, 379fof branched-chain amino acids, 266

thiamine and, 379fof pyruvate, 105, 109–111, 110f

Oxidative phosphorylation, 73, 73f, 77–80in catabolic pathways, 93concept map, 81finherited defects of, 80tightly coupled with electron transport,

77–78uncoupling from electron transport, 78–79

Oxidative reactions, irreversible, 145–146,146f

Oxidizing agent (oxidant), 76Oxidoreductases, 53fOxygen

hemoglobin affinity for and binding of,27–33, 28f, 41f

allosteric effectors and, 27, 29–332,3-bisphosphoglycerate and, 31–32,

31f, 32fcarbon dioxide binding and, 32carbon monoxide binding and, 32–33,

32fcooperative, 29–30, 29fPCO2 and, 29pH and, 30, 30fPO2 and, 29, 29f, 30saturation and, 28

molecularreactive intermediates of, 148–149,

148fin steroid hormone synthesis, 237,

238fmyoglobin affinity for and binding of,

28–29as nitric oxide synthase substrate, 151partial pressure of. See PO2

Oxygen debt, 104Oxygen dissociation curve

for hemoglobin, 29, 29f, 312,3-bisphosphoglycerate and, 32,

32fsigmoidal shape of, significance of,

30for myoglobin, 29, 29f

Oxyhemoglobin, 28Oxypurinol, 301

PPABA analogs, 294fPalindromes, 466Palmitate (palmitic acid)

elongation of, 187synthesis of, 184–186, 185f

relationship with glucosemetabolism, 186, 187f

Palmitic acid, 182f, 361Palmitoleic acid, 182fPalmitoyl CoA, energy yield from oxidation

of, 192, 193fPalmitoyl thioesterase, 186Pancreas, 307, 308fPancreatic enzymes

carbohydrate digestion by, 86, 87fdeficiency of, in cystic fibrosis, 174dietary nucleic acid degraded by, 298,

299fhormonal regulation by, 176, 176flipid processing by, 175–176protein digestion by, 248–249, 249f

Pancreatic islet cellsα, glucagon secretion by, 309, 313,

313fβ

destruction, in type 1 diabetesmellitus, 338, 338f

dysfunction, in type 2 diabetesmellitus, 342, 342f, 344,344f

glucose phosphorylation in, 98insulin secretion by, 307–308, 308f,

310fPancreatic lipase, 175Pancreatitis, chronic, 248Pancreozymin. See CholecystokininPantothenic acid, 54, 184, 381, 392–393f

in coenzyme A, 381, 381fdeficiency of, 381, 393fdietary intake of, 381

Dietary Reference Intakes for, 358ffunction of, 381, 392f

Parallel β sheet, 17, 17fParathyroid hormone (PTH), 388Parenteral feeding, 369Parietal cells, 248, 377Parkinson disease, 286Paroxysmal nocturnal hemoglobinuria, 206Partial pressure of carbon dioxide. See

PCO2Partial pressure of oxygen. See PO2Pathways, 91. See also specific pathwaysPCO2

oxygen affinity of hemoglobin and, 29,29f

sickle cell disease and, 36PCR. See Polymerase chain reactionPellagra, 380, 393fPenicillin, 62Pentasaccharide, core, in

oligosaccharides, 166, 166fPentavalent arsenic (arsenate), 101Pentose phosphate pathway, 92f,

145–156, 145f, 146fin absorptive/fed state, 323, 323f, 325,

325fconcept map, 155ffatty acid synthesis and, 186, 186firreversible oxidative reactions in,

145–146reversible nonoxidative reactions in, 147

Pentoses, 291, 292fPentose(s), in nucleosides, 292, 292fPEP. See PhosphoenolpyruvatePEP-carboxykinase (PEPCK), 118, 120, 122PEP-carboxylase, in fasting, 329PEP carboxylase (PEPCK), 457Pepsin

pH optimum for, 58in protein digestion, 248, 248f

Pepsinogen, 248Peptide bonds, 1, 1f, 13–14, 14f. See also

Polypeptidecharacteristics of, 14, 14fformation of, 13, 14fnaming, 14partial double-bond character of, 14, 14fpolarity of, 14, 14frigid and planar character of, 14, 14ftrans configuration of, 14, 14f

Peptide YY (PYY), 353Peptidyltransferase, 439, 440fPeripheral tissues

ketone body use by, 196, 197ftransport of ammonia from, 253, 253f

Peristalsis, 175Pernicious anemia, 377, 393fPeroxidase, 213Peroxisome, β-oxidation in, 195Peroxynitrite, 151PEST sequences, 247pH

enzyme denaturation and, 57optimum, for enzymes, 58, 58foxygen affinity of hemoglobin and, 29,

30–31, 30fprotons lowering, source of, 30, 30freaction velocity and, 57–58, 58fsickle cell disease and, 36

Phagocytosis, 150, 150fof extracellular glycosaminoglycans, 163oxygen-dependent, 150oxygen-independent, 150

Phenobarbital, 279Phenolic compounds, 365Phenylacetate, 271Phenylacetylglutamine, 258, 258fPhenylalanine

degradation of, 263, 263finherited deficiencies in, 263side chains of, 2ftyrosine and, 268

Phenylalanine hydroxylase (PAH), 263, 268,271–272, 287

deficiency in, 270–271, 270fgene for, mutation of, prenatal detection

of, 477, 479f, 480fPhenylbutazone, 214Phenylbutyrate, 258, 258fPhenylisothiocyanate, 15Phenylketonuria (PKU), 263, 268f, 269f,

270–272, 270fantenatal diagnosis of, 271–272characteristics of, 271, 271fmaternal, 272neonatal screening and diagnosis of, 270,

271prenatal diagnosis of, using RFLPs,

477–479, 479f, 480ftreatment of, 272


Index512

Phenyllactate, 271Phenylpyruvate, 271Phenylthiohydantoin (PTH), 15Pheochromocytoma, 286pH gradient, in oxidative phosphorylation,

77–78Phosphatase, 101Phosphate

addition of. See Phosphorylationinorganic (Pi)

as activator of PRPP synthase, 293,293f

in ATP synthesis, 73removal of. See Dephosphorylationvitamin D and, 388

Phosphatidalcholine, 202Phosphatidalethanolamine, 202, 202fPhosphatidic acid, 201, 201f, 202

synthesis of, 189f, 203Phosphatidylcholine, 201f, 234

in bile, 224in lung surfactant, 204synthesis of, 203–204, 204f

from phosphatidylserine in liver, 204,204f

Phosphatidylcholine:cholesterolacyltransferase (PCAT, LCAT),234–235, 236

Phosphatidylethanolamine, 201f, 204synthesis of, 203–204

Phosphatidylglycerol, 206Phosphatidylinositol, 205–206

as arachidonic acid reservoir, 205in membrane protein anchoring, 206, 206fin signal transmission across membranes,

205–206, 205fsynthesis of, 205–206

Phosphatidylinositol 4,5-bisphosphate (PIP2),205

Phosphatidylserine, 201f, 205synthesis of phosphatidylcholine from,

204, 204f3’-Phosphoadenosine-5’-phosphosulfate

(PAPS), 162, 210, 210f, 263Phosphodiesterase, 95–963’→5’-Phosphodiester bonds, 396–397, 396fPhosphodiester bonds, in RNA, 417Phosphoenolpyruvate (PEP), 102

glucagon and, 122, 122fin gluconeogenesis, 118–120, 119fin glycolysis, 102, 102f

Phosphofructokinasein absorptive/fed state, 323glucagon and, 122, 123in glycolysis, 102, 121, 138hormonal regulation of, 105, 105finhibition of, by citrate, 63, 98, 112insulin and, 313

Phosphofructokinase-1 (PFK-1)in absorptive/fed state, 321in gluconeogenesis, 120, 120fin glycolysis, 99, 100f

Phosphofructokinase-2 (PFK-2), 996-Phosphoglucanolactone dehydrogenase,

1466-Phosphoglucanolactone hydrolase, 146Phosphoglucomutase, 126, 128f, 1306-Phosphogluconate dehydrogenase, 1466-Phosphogluconate pathway. See Pentose

phosphate pathway6-Phosphogluconolactone, in pentose

phosphate pathway, 145–146, 146fPhosphoglucose isomerase, 99Phosphoglucose isomerase deficiency, 1032-Phosphoglycerate, dehydration of, 102

3-Phosphoglycerate, 101–102, 268Phosphoglycerate kinase, 102Phosphoglycerate mutase, 102Phosphoglycerides. See

GlycerophospholipidsPhospholipase A1, 207–208, 207fPhospholipase A2, 175, 207–208, 207f, 213,

214Phospholipase C, 205, 205f, 206, 207f, 208Phospholipase D, 207fPhospholipids

amphipathic nature of, 201in cell membranes, 201concept map, 217fdegradation of, 175–176, 207–208, 207f,

208fby pancreatic enzymes, 174, 174f

fatty acids as component of, 181functions of, 201in lipoproteins, 227, 228f, 232fmetabolism of, 173–180, 201–208remodeling of, 207–208structure of, 201–203, 201f, 202fsynthesis of, 203–207, 203f, 204f, 207f

Phospholipid(s), 173f, 201–208Phosphomannose isomerase, 138Phosphoprotein phosphatase, 63, 63f, 102,

2235’-Phosphoribosylamine, synthesis of, 2935-Phosphoribosyl-1-pyrophosphate (PRPP)

in purine synthesis, 293, 293f, 294fin pyrimidine synthesis, 302synthesis of, 292–293, 293f

Phosphorus, Dietary Reference Intakes for,358f

Phosphorylase kinase, 132activated a form of, 132, 133fcalcium-calmodulin complex and, 132,

133finactivated b form of, 132–133, 133f

Phosphorylationof enzymes, 63, 63fof eukaryotic translation initiation factor,

460, 460fof fructose, 137–138, 138fof fructose-6-phosphate, 99–100, 100fof galactose, 140of glucose, 98–99, 98fof HMG CoA reductase, 223, 223finherited defects of, 80oxidative, 73, 73f, 77–80

in catabolic pathways, 93concept map, 81ftightly coupled with electron transport,

77–78uncoupling from electron transport,

78–79of proteins, 443f, 444sterol-independent, 223, 223fsubstrate level, 98, 102, 112

Photosensitivity, in porphyria, 280Phylloquinone (vitamin K1), 389Physical activity. See ExercisePhytanic acid, 195, 195fPigmentation disorders

in alkaptonuria, 274in phenylketonuria, 271

Pineal gland, 287Pituitary hormones, in steroid hormone

synthesis, 239, 239fPlacenta, hormonal secretion by, 237Plant protein, 367, 367fPlant sterols, 220Plasma assays, 65Plasma enzymes

classification of, 64as diagnostic tool, 65elevated levels of, 65

in disease states, 64f, 65in normal cell turnover, 64–65, 64f

Plasma hormones, 307Plasma lipoproteins, 227–237. See also

Lipoprotein(s)Plasmalogens, 202, 202fPlasmids, 398

prokaryotic, 467, 467f, 468fPlasminogen, apo(a) and, 237Plasmodium falciparum, 37Platelet-activating factor (PAF), 202, 202fPlatelet aggregation

n-6 and n-3 polyunsaturated fats and,363, 363f

nitric oxide as inhibitor of, 150, 151fPlatelet homeostasis, prostaglandins in, 214,

216fPlatelet(s), interaction of prothrombin with,

389Pneumonia, nutrition and, 361fPO2, oxygen affinity binding and

of hemoglobin, 29, 29fof myoglobin, 29, 29f

Pol α, 407, 407fPolar amino acids

in myoglobin, 26uncharged, 3f, 4

Polar hydroxyl group, in amino acid sidechains, 4

Polarity, of peptide bond, 14, 14fPolar side chains, 3fPol β, 407, 407fPol δ, 407, 407fPol ε, 407, 407fPol γ, 407, 407fPol 5’→3’ polymerase, 407Polyadenylate polymerase, 426Polyadenylation, 457Poly-A tail, of mRNA, 426, 426fPolycistronic mRNA, 438, 450, 452Polydipsia, in diabetes mellitus, 338, 3415’→3’ polymerase, in DNA proofreading,

404–405, 404fPolymerase chain reaction (PCR), 479–483

advantages of, 382applications of, 482–483for comparison of normal cloned gene

with uncloned mutant gene, 482in cystic fibrosis, 483, 483ffor detection of low-abundance nucleic

acid sequences, 482for forensic analysis of DNA samples,

482–483primer construction in, 480–481, 481fsteps in, 480–482

Polymorphism(s), 475, 475f. See alsoRestriction fragment lengthpolymorphism

in phenylketonuria, 477–479for prenatal diagnosis, 476–479restriction fragment length, 473–479short tandem repeat, 483in sickle cell disease, 476–477, 478fsingle nucleotide, 475in tandem repeats, 475, 476ffor tracing chromosomes from parent to

offspring, 475–476Polynucleosome, 411Polyol, 139Polypeptide chains, 431, 431f

posttranslational modification of,443–444, 443f


Index 513

Polypeptide(s), 14α-helix of, 16–17, 16famino acid composition of, determination

of, 14–15, 15f, 16famino acid residue or moiety in, 14β bends of, 17β-sheets of, 17, 17fcleavage into smaller fragments, 15, 16fdomains of, 19elongation of, 439–442, 439fmRNA translation into, 431–438posttranslational modification of, 443–444,

443–444fprimary structure of, 14–16secondary structure of, 16–18

nonrepetitive, 18sequencing of, from N-terminal end, 15,

15ftertiary structure of, 18–20

interactions stabilizing, 19Polyphagia, in diabetes mellitus, 338, 341Polyphosphorylated guanosine (ppGpp), 454Polysaccharide(s), 83, 85

dietary, 365digestion of, 86

Polysomes, 442, 442fPolyubiquitin chain, 247Polyunsaturated fatty acids (PUFA), 188, 364fPolyuria, in diabetes mellitus, 338, 341Pompe disease, 129f, 131, 472Porphobilinogen, 278, 278f, 279, 279fPorphyria cutanea tarda, 280, 280f, 281fPorphyria(s), 279–282

acute intermittent, 280, 281fchronic, 280, 281fclinical manifestations of, 280erythropoietic, 280, 281f

congenital, 280, 281fhepatic, 280

acute, 280hereditary coproporphyria, 280, 281ftreatment of, 282variegate, 280, 281f

Porphyrinogens, 278Porphyrin(s)

degradation of, 282–284, 282f, 283f, 284fmetabolism of, 277–278side chains of, 277

distribution of, 278, 278fstructure of, 277–278, 278fsynthesis of, 278–279, 278f, 279f, 280f,

281fdefects in, 279–282, 280fend product inhibition by hemin,

278–279rate-controlling step of, 278

type I, 278, 278ftype II, 278, 278f

Positive regulation, of gene expression, 452,453

Postprandial hypoglycemia, 316Posttranscriptional modification, 424–427

of ribosomal RNA, 424–425, 424fof transfer RNA, 425, 425f

Posttranslational modificationof collagen, 45of polypeptide chains, 443–444, 443f

Pravastatin, 61, 224Prednisone, 301Pregnancy

folic acid supplementation in, 375retinoid/vitamin A toxicity in, 386

Pregnenolone, 237f, 238Premature atherosclerosis, 232Prenatal diagnosis, 476–479

of cystic fibrosis, 483, 483fDNA sources, 476, 477fmethods, 476of phenylketonuria, 477–479, 479f, 480fof sickle cell disease, 476–477, 478f

Prenylation, 221Prepriming complex, for DNA replication, 399,

403Preproglucagon, 313Preproinsulin, 308, 308f, 309fPreribosomal RNA, 424Pribnow box, 420, 420fPrimaquine, 153Primary hyperoxaluria Type 1, 253Primase, 402–403, 402fPrimosome, 403Prion disease, 22, 22fPrion protein (PrP), 22, 22fPro-α-chains, in collagen synthesis, 45, 46fProbenecid, 301Probes, DNA, 470–472

antibodies, 472biotinylated, 472hybridization to DNA fragments, 470oligonucleotide, 471–472, 472f

in sickle cell disease, 472, 473fProcollagen, 46f, 47

extracellular cleavage of, 46–47f, 47Procollagen peptidases, 47, 47f

deficiency of, and Ehlers-Danlossyndrome, 48

N-Procollagen peptidases, 47Product inhibition, 64fProgesterone, 237f, 240fProgestins, 237Proinsulin, 308, 308f, 309fProkaryotic DNA, 395

chain elongation in, 403–405, 403flagging strand of, 402, 403fleading strand of, 402, 403fproofreading of, 404–405, 404fproteins required for strand separation in,

399–400, 400freplication fork of, 399–400, 400freplication of, 399–406

bidirectional, 399, 400fcontinuous, 402direction of, 402discontinuous, 402, 402forigin of, 399, 400fprepriming complex for, 399, 402processive, 403RNA primer for, 402–403, 402f

excision and replacement of, 405,405f, 406f

semiconservative, 399, 399fsupercoil problem in, 400–401, 401f

Prokaryotic gene expression, regulation of,449f, 450–454, 463f

coordination of transcription andtranslation, 453–454, 454f

lactose operon in, 450–452, 451fmRNA transcription from bacterial

operons, 450role of operators, 450, 451ftryptophan operon in, 452–453, 453f

Prokaryotic gene transcription, 419–421antibiotics targeting, 421, 422felongation in, 420–421, 420fhairpin turn in, 421, 421finitiation of, 419–420, 420fregulation of, 449f, 450–454termination of, 421, 421f

rho-dependent, 421rho-independent, 421, 421f

Prokaryotic plasmids, 467, 467fProlactin, 142Proliferating cell nuclear antigen (PCNA), 407Proline, 4, 4f, 262

α-helix disrupted by, 16–17in β-bends, 17catabolism of, 262in collagen, 45

hydroxylation of, 45, 45f, 46f, 47degradation of proteins containing, 247in elastin, 49side chains of, 2f, 4, 4fsynthesis of, 268

Prolyl hydroxylase, hydroxylation in collagenby, 45f, 47

Promoter activation, hormone responseelements and, 240, 241f

Promoter region, 419–420, 420fPromoters, 422–423, 423fPropeptides, in collagen biosynthesis, 47, 47fPropionate, 277Propionic acid, 182fPropionyl CoA, 265

amino acid catabolism forming, 265, 266fconversion to succinyl CoA, 265metabolism of, 194–195, 195f

Propionyl CoA carboxylase, 194Prostacyclin, 213fProstaglandin endoperoxide synthase (PGH

synthase), 213Prostaglandin(s), 213–214

concept map, 217ffatty acids as precursors of, 181function of, 215fn-6 and n-3 polyunsaturated fats and, 363PGE2, 213f, 215fPGF2α, 213f, 215fPGG2, 214fPGH2, synthesis of, 213, 214fPGI2, 213, 213f, 214, 215fin platelet homeostasis, 214structure of, 213fsynthesis of, 213–214, 215f

inhibition of, 214substrates for, 202

Prosthetic group, 54Proteases, 50Proteasomes, 246–247, 444Protein-calorie malnutrition (PEM), 369Protein C vitamin K, 390Protein Digestibility Correct Amino Acid Score

(PDCAAS), 367, 367fProtein factors, 437Protein kinase A, 95, 134Protein kinase A-mediated covalent

modification, 456–457Protein kinase C, 95, 134, 208

in intracelluar signaling, 205f, 206Protein kinase G, 151Protein kinase(s)

cAMP-dependent, 95, 95fglucagon and, 314in glycogen degradation, 132, 133,

133fin pyruvate kinase regulation, 102,

102fin phosphorylation, 63, 63fpyruvate as inhibitor of, 111in pyruvate dehydrogenase complex, 111f

Protein-oligosaccharide transferase, 167Protein phosphatase 1, 132, 133, 134Protein phosphatase(s), 95Protein(s)

α-helix of, 16–17, 16famino acid sequence, 14–16


514

determination of, 14–15, 15fDNA analysis of, 15–16

amino acid sequence in, 14–16determination of, 14–15, 15fDNA analysis of, 15–16

analysis of, 484–485, 485fβ-bends of, 17β-sheets of, 17, 17fcarboxylation of, 444, 444fcovalent modification of, 444degradation of, 246–247, 444

chemical signals for, 247ubiquitin-proteasome mechanism for,

246–247, 247fdenaturation of, 20

agents for, 20reversibility of, 20

dephosphorylation of, 95dietary, 246f, 357, 357f, 367–369


from animal sources, 367, 367fdeficient intake of, 369, 369fwith differing limiting amino acids, 368,

368fdigestion of, 247–249

abnormalities in, 248–249by gastric secretion, 248, 248fby pancreatic enzymes, 248–249,

249fenergy content of, 359, 359fexcessive intake of, 368nitrogen balance and, 368from plant sources, 367f, 368quality of, 367–368, 367f, 368frequirement for, 368–369sparing effect of carbohydrates and,

369DnaA, 399DNA helicases, 400, 400fdomains of, 19farnesylated, 444, 444ffibrous, 43–52, 51f. See also Collagen;

Elastinsummary, 52

folding of, 20, 20fchaperones in, 20errors or mutations in

function of, 1γ-carboxyglutamate in, 389–390globular, 18, 25–42. See also Hemoglobin;

Myoglobinglycosylation of, 443f, 444hydroxylation of, 444, 444flocation of nonpolar side chains in, 2, 4, 4fmetabolism of

in fasting, 332, 332fglucagon and, 314

monomeric, 20native conformation of, 23fpeptide bonds of, 13–14, 14fphosphorylation of, 443f, 444posttranslational modification of, 443–444,

443f, 444fribosomal, 436

regulatory, 454, 454fsingle-stranded DNA-binding (SSB), 400,

400ffor strand separation, 399–400, 400fstructure of, 13–24

in aqueous solution, 18concept map, 23fhierarchy of, 13, 13f, 23fmisfolding, 21–22primary, 13–16, 13f, 14f, 15f, 23f

quaternary, 13f, 20–21, 23fsecondary, 13f, 16–18, 16f, 17f, 23f

nonrepetitive, 18supersecondary (motifs), 18, 18ftertiary, 13f, 18–20, 18f, 19f, 20f, 23f

interactions stabilizing, 19synthesis of, 395, 431–448, 440–441f.

See also Gene expressionin absorptive/fed state, 323f, 324, 326,

326fcomponents required for, 434–437concept map, 446felongation in, 439–442, 439f, 440finhibitors of, 442initiation of, 438–439, 440finsulin and, 311regulation of, 443steps in, 438–443termination of, 441f, 442

trimming of, 443uncoupling, 79

Protein-sparing effect, 369Protein targeting, 45, 166, 443Protein turnover, 246–247, 246f, 259f

rate of, 246Proteoglycan aggregates, 158, 160fProteoglycan monomers, 158

brush-bottle model of, 158, 160fstructure, 158, 160f

Proteoglycan(s), 157cartilage, 158, 160fglycoproteins vs., 165linkage region of, 158, 160fstructure of, 158, 160f

Proteolytic enzymes, 248, 248fProteomics, 484, 485, 485fProthrombin, 389Proton acceptors, amino acids as, 5Proton donors, amino acids as, 5“Proton leak,” 79Proton pump, 77–78Proton transport, coupled with electron

transport, 77–78, 78fProtoporphyria, erythropoietic, 280, 281fProtoporphyrin, 62, 277Protoporphyrin IX, 279fProtoporphyrinogen oxidase, 281fPRPP synthetase, 293, 299Pruritus,

in porphyria, 280treatment of, 385

PS decarboxylase, 204Pseudogenes, 34Pseudouridine, 425fP sites, on ribosome, 436Psoriasis, retinoic acid for, 385Purine nucleoside phosphorylase, 299

deficiency in, 300Purine nucleotides

degradation of, 298–302, 300f, 305fdiseases associated with, 299–302,

300f, 301fparent, inosine monophosphates as, 293purine base conversion to, 296, 296fsalvage pathway for, 296–297, 296fstructure of, 291–292, 291f, 292fsynthesis of, 292–297, 305f

committed step of, 293, 294fdrugs targeting, 293, 294f, 305f

Purine ring, atom sources for, 292, 293fPurine(s)

ammonia from, 257bases

conversion to nucleotides, 296, 296fin DNA and RNA, 291–292, 291f, 305f

de novo synthesis of, 291Puromycin, 440fPyranose, 84Pyridoxal, 377f, 378Pyridoxal phosphate, 251, 251f, 377f

in glycogen degradation, 128in histamine synthesis, 287in sphingomyelin synthesis, 206in transamination of amino acids, 251,

251fPyridoxamine, 377f, 378Pyridoxine, 273, 377f, 378, 378. See also

Vitamin B6Pyrimidine nucleotides

degradation of, 304formation of, 302–303, 303fsalvage of, 304structure of, 291–292, 291f, 292fsynthesis of, 302–304, 303f, 305f

Pyrimidine ring, sources of individual atomsin, 302, 302f

Pyrimidine(s)ammonia from, 257bases, in DNA and RNA, 291–292, 291f,

305fdegradation of, 304de novo synthesis of, 291salvage of, 304structure of, 291–292, 291f, 292fsynthesis of, 302–303, 303f

Pyrophosphatase, 126, 296, 437Pyrophosphate (PPi), 404Pyruvate, 96

alternate fates of, 105amino acids that form, 263, 263fcarboxylation to oxaloacetate, 105,

118–119, 119fNADPH production in, 186, 186f

formation ofin amino acid catabolism, 261, 263,

263fATP-producing, 102–103

glucose conversion to (aerobic glycolysis),96–102, 96f

glucose synthesis from (gluconeogenesis),118–119, 119f

oxidative decarboxylation of, 105, 106f,109–111, 110f

thiamine and, 378f, 379, 379fphosphoenolpyruvate conversion to, 102reduction to ethanol, 105, 106freduction to lactate (anaerobic glycolysis),

103–104, 103fin tricarboxylic acid, 109–111

Pyruvate carboxylase, 105, 106f, 118, 120,122, 123

in absorptive/fed state, 323allosteric regulation of, 119in fasting, 330

Pyruvate carboxylase/PEP carboxykinase,121

Pyruvate decarboxylase, 147Pyruvate dehydrogenase complex, 105, 106f,

109–111, 110fcoenzymes in, 110component enzymes in, 110deficiency in, 111mechanism of action, 110, 110fregulation of, 110–111, 111fin tricarboxylic acid cycle, 109–111

Pyruvate dehydrogenase kinase, 110, 323Pyruvate dehydrogenase (PDH), 105, 110,

110f, 119in absorptive/fed state, 323in arsenic poisoning, 101, 111

Index


Index 515

deficiency of, 111in fasting, 196, 330inhibition of, by acetyl CoA, 122irreversibility of action, 118

Pyruvate dehydrogenase phosphatase,110–111

Pyruvate kinase, 98, 102, 118in absorptive/fed state, 323activation of, 102covalent modification of, 102deficiency in, 102–103dephosphorylation of, 102glucagon and, 121, 122fhormonal regulation of, 105insulin and, 313mutant forms of, 103

QQuinolones, 401

RRacemases, 84Random coil, 18Rate of reaction, 55Reactive oxygen species, 148–149, 148f

in porphyria, 280Receptor-mediated endocytosis, 232, 233fRecombinant DNA, 472

joining of sticky ends, 467fRecommended Dietary Allowance (RDA),

357, 358ffor carbohydrates, 367for protein, 368for vitamin D, 388for vitamin E, 391

Red blood cells2,3-bisphoglycerate synthesis in, 101G6PD in, 152, 152f

deficiency of, 152, 152fhemoglobin in, 27NADPH in, 148

Redox pairs, 76Reducing agent (reductant), 76Reducing equivalents, transport of, 79–80,

79fReducing sugars, 84–85Reduction potential, standard (Eo), 77, 77f

relationship with free energy change, 77Redundancy, 433Refsum disease, 195Regulatory sequences, in transcription,

449–450RelA, 454Release factor (RF), 441f, 442Renal osteodystrophy, 389Renal rickets, 389Renaturation (reannealing), 398Renin, 239Replication fork, 399–400, 400fReproductive tissues

cholesterol synthesis in, 220vitamin A and, 384

Respiratory burst, 150Respiratory control, of energy production, 78Respiratory distress syndrome, 204, 236Resting metabolic rate (RMR), 359Restriction endonucleases, 465–466, 465f

nomenclature for, 466restriction sites, 466specificity of, 465–466, 466f“sticky” and “blunt” ends, 466, 466f, 467f

Restriction fragment length polymorphism(RFLP), 473–479

close linkage in, 477DNA variation resulting in, 475, 475f, 476f

in phenylketonuria, 477–479, 479ffor prenatal diagnosis, 476–479, 477fin sickle cell disease, 476–477, 478fof single DNA base changes, 474, 475of tandem repeats, 475, 476ffor tracing chromosome from parent to

offspring, 475–476Restriction fragment(s), 465–466

sticky and blunt ends of, 266, 266fRestriction map, 467Restriction sites, 466Reticuloendothelial (RE) system, heme

degradation in, 282, 282fRetinal, 382, 382f, 392f

11-cis, 382f, 383f, 38411-cis-Retinal, 382f, 383f, 384Retinoic acid, 381–382, 382f, 392f

mechanism of action, 382, 384freproduction and, 384retinol oxidation to, 384fin transcriptional regulation, 456use in dermatology, 385, 385f, 386

Retinoids, 381–384clinical indications for, 384–385function of, 384mechanism of action, 382, 383f, 384f,

385fstructure of, 382, 382ftoxicity of, 385–386, 393f

Retinol, 382, 382f, 392fas dietary supplement, 384, 391oxidation to retinoic acid, 384f

Retinol-binding protein (RBP), 382cellular, 382plasma, 382, 384f

Retinopathy, 140Retinopathy, diabetic, 345, 346fRetrotransposons, 408, 461Retroviruses, 459, 468Reverse transcriptase, 408, 469, 469fReyes syndrome, 193RFLP. See Restriction fragment length

polymorphismR-group. See Side chains, of amino acidsRho-dependent termination, 421Rhodopsin, 384Rho factor, 419Rho-independent termination, 421, 421fRiboflavin, 54, 380–381, 392–393f

active forms of, 380–381, 380f, 392fdeficiency of, 381, 393fDietary Reference Intakes for, 358ffunction of, 381, 392f

Ribonucleases, 397, 424Ribonucleoside 5’-diphosphate (NDP), 293fRibonucleoside 5’-monophosphate (NMP),

293fRibonucleoside phosphates, 291. See also

Nucleotide(s)Ribonucleoside 5’-triphosphate (NTP), 293fRibonucleotide reductase, 297, 300f

activity site of, 297–298, 298freduced, regeneration of, 297regulation of, 297–298, 298fsubstrate specificity of, 298

Ribonucleotide(s)conversion to deoxyribonucleotides,

297–298, 297fas end product of purine synthesis, 293

Ribose, 292, 292fRibose 5-phosphate, 145

formation of, in pentose phosphatepathway, 147, 147f

Ribosomal proteins, 436regulatory, 454, 454f

Ribosomal RNA (rRNA), 418, 418fposttranscriptional modification of,

424–425, 424fstringent response and, 454

Ribosomes, 436–437cellular locations of, 436–437eukaryotic, 436–437, 436fprokaryotic, 436–437, 436f

Ribozymes, 54, 434, 439Ribulose 5-phosphate, 145, 147

formation of, 146, 146fRicin, 442Rickets, 393f

nutritional, 388renal, 389

Rifampin, 421, 422fRNA, 395, 417–430

alkali cleavage of, 396analysis of, 485fbases of

purine, 291, 291f, 305fpyrimidine, 291, 291f, 305funusual, 291–292, 292f, 418

concept map, 429fDNA information for, 395, 395felongation of, 420–421, 420fheterogeneous nuclear, 425messenger (mRNA), 417, 418, 419f

alternative splicing patterns of, 427,428f

coding for protein synthesis, 434codons of, 431–432, 432f

mutations of, 432f, 433–434recognition by tRNA, 435

editing, 457–458, 457feukaryotic, 418, 419f

posttranscriptional modification of,425–427, 426f, 454,457–460

exons of, splicing of, 426–427, 427fframe-shift mutation of, 434, 434fintrons of, 426

removal of, 426–427, 427flevels of, determination of, 483–484,

484fmissense mutation of, 432f, 433monocistronic, 438non-coding (ncRNA), 417nonsense mutation of, 432f, 433nucleotide sequence of, alternation of,

432f, 433–434polycistronic, 438, 450, 452silent mutation of, 432f, 433splice site mutation of, 434stability of, 458–460, 458f, 460ftranscription of, 450translation of, 431f, 432–443,

440–441f, 460, 460fcomponents required for, 434–437regulation of, 443steps in, 438–444, 440–441f

trinucleotide repeat expansion of, 433,433f

posttranscriptional modification of,424–427

preribosomal, 424ribosomal (rRNA), 417, 418, 418f

posttranscriptional modification of,424–425, 424f

in regulation of gene expression, 454,454f

small nuclear (snRNA), 418, 426–427,427f

structure of, 417–418, 429fsynthesis of (transcription), 429f. See also


516 Index

Gene expressionantibiotics targeting, 421, 422ffrom bacterial operons, 450–453, 451fDNA palindrome and, 466, 466felongation in, 420–421, 420feukaryotic, 420–422, 454–461hairpin turn in, 421, 421f, 453initiation of, 419–420, 420fnegative regulation of, 453positive regulation of, 452, 453primary transcript inprokaryotic, 419–421, 450–454termination of, 421, 421f

transfer (tRNA), 417, 418, 418fas adaptor molecules, 435anticodon of, 435antiparallel binding with codon, 437,

437fattachment of amino acids to


codon recognition by, 435initiator, 438, 440fintrachain base pairing of, 418, 418fposttranscriptional modification of, 425,

425fin protein synthesis, 435ribosomal binding sites for, 436synthesis of, 425unusual bases of, 417f, 418, 425

RNA-induced silencing complex (RISC), 459RNA interference (RNAi), 459, 459f

therapy using, 459–460RNA polymerase, 417

antibiotics targeting, 421, 422fcore enzyme of, 419, 419fDNA unwinding by, 420–421, 420fin eukaryotic transcription, 422–424, 423fholoenzyme (sigma factor, unit) of, 419,

419fmitochondrial, 424nuclear, of eukaryotic cells, 422–424, 423fin prokaryotic transcription, 419–421, 419f,

450–452, 451frho factor of

consensus nucleotide sequencesrecognized by, 419–420, 420f

transcription termination dependent on,421, 421f

5’→3’ RNA polymerasein transcription, 419–421, 420f

RNA polymerase I, 422RNA polymerase II, 422–424, 425

inhibitors of, 424RNA polymerase III, 424RNA primers, 402–403, 402f

excision of, 405, 406fRNase H, 406RNA silencing, 459Rosuvastatin, 224Rotenone, 76fRT-PCR (reverse transcriptase-PCR), 483

SS-adenosylhomocysteine, 264S-adenosylmethionine (SAM), 204, 263,

425–426activated methyl group of, 264as carrier of one-carbon units, 263, 267hydrolysis of, 264–265, 264fmethylation of, 460, 461fsynthesis of, 264, 264f

Salicylates, 282Salt bridges, 31

Salvage enzymes, 409Sandhoff’s disease, 212fSanfilippo syndrome, 164fSanger dideoxy method, 470, 471fSaturated fat, 361, 362f, 364fSaturnine gout, 299Scaly dermatitis, 182Scavenger receptor class A (SR-A), 234Scavenger receptor class B type 1 (SR-B1),

236Sclera,

blue, 49yellow, 284

Scrapie, 22Scurvy, 47, 47f, 377, 377f, 393fSecond messenger systems, 94Secretin, 176, 248Sedimentation coefficients, of ribosomes, 436Selenium, Dietary Reference Intakes for, 358fSemiconservative replication, of DNA, 399,

399fSenescence, cellular, 408, 408fSerine, 4, 19f

catabolism of, 263, 263fin cysteine synthesis, 265, 268degradation of proteins containing, 247interconversion with glycine, 263, 263f, 268in phospholipids, 201f, 202in proteoglycans, 158side chains of, 3f, 4in sphingomyelin synthesis, 206, 207fsynthesis of, 268

Serine dehydratase, 263Serine hydroxymethyl transferase, 268Serotonin

functions of, 287monoamine oxidase inhibitors and, 287synthesis of, 270f, 287, 287f

Serum assays, 65Set point, for body weight, 351Settling point, for body weight, 351Severe combined immunodeficiency disease

(SCID)gene therapy for, 485, 486fX-linked, 485

Severe combined immunodeficiency (SCID),300f, 301–302

Sex-hormone binding protein, 237Sex hormone(s), 237Shine-Dalgarno sequence, 438f, 439, 454Short-chain fatty acids, 192Short tandem repeat polymorphisms (STRs),

483Sialic acid. See N-Acetylneuraminic acidSickle cell anemia

jaundice and, 284Sickle cell disease, 4, 35–37, 42f

amino acid substitution in HbS and, 36, 36fanoxia caused by, 36, 37fdiagnosis of, using RFLPs, 476–477, 478felectrophoresis in, 36, 36fethnicity and, 35oligonucleotide probes and, 472, 472f, 473fpoint mutation in β-globin gene causing, 35,

37fselective advantage of heterozygous state,

37, 38ftreatment of, 36, 298variables increasing sickling in, 36

Side chainsof amino acids, 1–5, 1f, 2–3f

acidic, 3f, 5as attachment site for other

compounds, 4

basic, 3f, 5in disulfide bonds, 4hydrogen bonding by, 4, 19, 19fhydrophilic, 18hydrophobic, 18hydrophobic interactions of, 4, 19, 19fionic interactions of, 19, 19fnonpolar, 2–4, 2f, 4f

location in proteins, 2, 4, 4fpolar, 3f, 4uncharged polar, 3f, 4

of porphyrins, 277–278distribution of, 278, 278f

Sigma factor, 419Signal transmission

ceramides in, 208insulin in, 311f, 312phosphatidylinositol in, 205–206, 205fsecond messengers in, 94–96, 291sphingosine in, 208, 208f

Sildenafil citrate, 151Silencers, 424Silent mutation, 432f, 433Simvastatin, 61, 224, 224fSingle nucleotide polymorphisms (SNPs), 475Single-stranded DNA-binding (SSB) proteins,

400, 400fβ-Sitosterol, 220Skeletal muscle

calcium and, 131–132, 132fcarnitine deficiency in, 192contraction of, 131exercising, glycogen as fuel source for, 332glycogen in, 125–126, 126f, 131–132, 131f,

133flactate formation in, 103, 118lipoprotein lipase in, 228myoglobin in, 26resting

in absorptive/fed state, 325–326, 326famino acid metabolism in, 326, 326fcarbohydrate metabolism in, 326,

326ffat metabolism in, 326, 326fintertissue relationships of, 328f

in fasting, 331–332, 332fcarbohydrate metabolism in, 331,

332flipid metabolism in, 332, 332fprotein metabolism in, 332, 332f

fatty acids as fuel source for, 332oxygen consumption of, 326

Sly syndrome, 164fSmall intestine

dietary lipid processing in, 175dietary nucleic acid degradation in, 298,

299foligopeptide digestion in, 249

Small interfering RNA (siRNA), 459Small nuclear ribonucleoprotein particles

(snRNPs), 427, 427fSmall nuclear RNA (snoRNA), 418, 422,

424–425, 427fSmith-Lemli-Opitz syndrome (SLOS), 221Smooth muscle, nitric oxide and relaxation of,

150–151, 151fSodium azide, 76fSodium-dependent glucose co-transporter 1

(SGLT-1), 87Sodium-glucose linked transporter (SGLT), 97Sodium (Na+)-independent facilitated diffusion

transport, of glucose, 96–97, 97fSodium (Na+)-monosaccharide


Index 517

cotransporter system, 96, 97Sorbitol, 345

and diabetes, 345glucose conversion to fructose via,

139–140, 140fhyperglycemia and, 140synthesis of, 139–140

Sorbitol dehydrogenase, 139, 140Southern blotting, 473, 485f

detection of mutations, 473experimental procedure, 473, 474fvariants of, 473

Soy protein, coronary heart disease and, 364Sperm cells, fructose metabolism in, 139–140S phase, of cell cycle, 407, 407fSphinganine, 203fSphingolipidoses, 210–213, 211–213, 211f,

212fSphingolipids. See GlycosphingolipidsSphingomyelin, 202–203, 203f

degradation of, 208, 208fdisorders of, 208, 208f

ratio with phosphatidylcholine, inrespiratory distress syndrome, 204

synthesis of, 206–207, 207fSphingomyelinase, 208Sphingophospholipids, 202–203Sphingosine, 201Spina bifida, 265, 375Spleen, heme degradation in, 282, 282fSpliceosome, 426Splice site mutations, 427, 434Splicing, 426

alternative, 457, 457fmechanism of, 427, 427fsplice-site choice, 457

Squalene, 221Starch

dietary intake of, 365digestion of, 85

Starvation. See Fast/fastingStatin drugs, 224, 361

competitive inhibition by, 61, 61fStearic acid, 182f, 361Steatorrhea, 177, 178f, 248Stercobilin, 283Steroid, 173fSteroid hormones, 237–240, 237f

action mechanism of, 240, 240f, 241fadrenal cortical

secretion of, 239, 239fdeficiencies of, 238, 238fdegradation of, 240excretion of, 240gonad secretion of, 240metabolism of, 240synthesis of, 237–238, 238f

cholesterol in, 237–238rate-limiting step of, 237

transport of, 237Steroid nucleus, 219

hydroxylation of, 237Steroidogenic acute regulatory protein (StAR),

238Sterol regulatory element-binding protein

cleavage activating protein (SCAP),223

Sterol regulatory element-binding protein(SREBP), 222–223, 223f, 232

Sterol regulatory element (SRE), 222–223,223f, 232

Sterol(s), 219–220in HMG CoA reductase regulation,

222–223, 223f

neutral fecal, 224plant, 220

Sticky ends, of DNA fragment, 466, 466f, 467fStoichiometry, of urea cycle, 255–256Stomach

digestion of proteins in, 248lipid processing in, 173–174

Stop codons, 432Strand-directed mismatch system, for DNA,

411, 411fStreptomycin, 440fStress response, ACTH in, 239Stringent factor, 454Stringent response, 454, 454fStroke, nutrition and, 361fStructural motifs, 450Substrate concentration

in absorptive/fed state, 321, 321fin fasting, 329reaction velocity and, 57, 57f

Michaelis-Menten equation for, 58–59,58f, 59f

Substrate-level phosphorylation, 98, 102, 112Succinate, 112f

oxidation of, 112f, 113Succinate dehydrogenase, 76, 80, 80f, 113Succinate thiokinase (succinyl CoA synthase),

112–113Succinyl CoA, 265

α-ketoglutarate conversion to, 112, 112fcleavage of, 112–113, 112fformation of, in amino acid catabolism,

263–265, 264fin porphyrins, 278propionyl CoA conversion to, 265synthesis of, 194–195

Succinyl CoA:acetoacetate CoA transferase(thiophorase), 197

Sucrase, 87Sucrose, 85, 365, 367Sudden infant death syndrome (SIDS), 193Sugar(s). See also Disaccharide(s);

Monosaccharide(s);Oligosaccharide(s); Polysaccharide(s)

acidicin glycosaminoglycans, 157, 157f, 161,

162fsynthesis of, 161, 162f

added, 365amino


synthesis of, 160, 161fD- and L-, 84, 84fdietary intake of, 365

disease and, 367reducing, 84–85

Sulfamethoxazole, 153Sulfate groups

addition of, in glycosaminoglycans, 162addition of, in glycosphingolipids, 210, 210fin sulfatides, 210

Sulfatides, 210Sulfhydryl groups, 18f, 19Sulfinpyrazone, 301Sulfoglycosphingolipids, 210Sulfonamides, 282

purine synthesis inhibited by, 293, 294ftetrahydrofolate synthesis inhibited by, 374f

Sulfonylureas, 310Sulfotransferases, 162, 210Supercoils (supertwists), 400–401, 401fSupermouse, 486Superoxide, converted into hydrogen peroxide,

150Superoxide catalase, 148Superoxide dismutase (SOD), 74, 148, 150Superoxide radicals, 151Supersecondary structures, 18, 18fSurfactant, 207

phosphatidylcholine and, 204in respiratory distress syndrome, 204

Surgery, weight-reduction, 355Svedberg units, of rRNA, 418Symbols, for amino acids, 5, 5fSympathetic ganglia, tyrosine hydroxylase in,

286Synaptic signaling, 94fSyndecan, 158Synthetic uncouplers, 79Systemic lupus erythematosus, 427

TTAG synthase, 176Tandem repeats, 475, 476fTangier disease, 236Taql, specificity of, 466, 466fTaq polymerase, 482TATA box, 423Tau protein, 21Taurine, bile acids conjugated to, 225, 225fTaurochenodeoxycholic acid, 225, 225fTaurocholic acid, 225Tay-Sachs disease, 211, 212fTelomerase, 407–408, 408fTelomeres, 407–408Temperature

enzyme denaturation and, 57melting

of DNA, 398, 398fof fatty acids, 182

reaction velocity and, 57, 57fTermination codons, 432, 432fTermination factor, 419Testes, hormonal secretion by, 237, 239–240,

239fTestosterone, 237, 237f, 239, 240fTetanus toxin, cell surface receptors for, 209Tetracyclines, 440fTetrahydrobiopterin (BH4), 151, 268, 270fTetrahydrofolic acid (THF). See also Folic acid

in one-carbon metabolism, 267, 267fsynthesis of, inhibition of, 374f, 375in thymidine monophosphate synthesis,

303, 304fvitamin B12 deficiency and, 376

Thalassemia(s), 38–39α, 39, 39f, 42f

hemoglobin H disease and, 39, 39fhydrops fatalis and, 39, 39fsilent carriers of, 39

β, 38–39, 38f, 42f, 427major, 39minor, 39

Thermogenin, 79Thermus aquaticus, 482Thiamine, 378–379, 392–393f

active form of, 378, 378f, 392f. See alsoThiamine pyrophosphate

clinical indications for, 379as coenzyme, 378, 379fdeficiency of, 379, 393fDietary Reference Intakes for, 358ffunction of, 378structure of, 378, 378f

Thiamine pyrophosphate (TPP)as coenzyme

for α-ketoglutarate dehydrogenase


Index518

complex, 112, 378, 378f, 379ffor branched-chain α-ketoacid

dehydrogenase, 266ffor pyruvate dehydrogenase complex,

110, 378, 378f, 379fThiamine pyrophosphate (TPP)-requiring

enzymes, 147Thiazide diuretics, 299Thiogalactoside transacetylase, 450Thiokinases, 176, 189, 190Thiophorase, 197Thioredoxin, 297, 297f

reduced, regeneration of, 297, 297fThioredoxin reductase, 297, 297f-35 sequence, 420, 420fThreonine, 4

catabolism of, 263, 265degradation of proteins containing, 247side chains of, 3f, 4

Thrombogenesisn-6 and n-3 polyunsaturated fats and, 363,

364fprostaglandins and, 214

Thromboxane(s), 213–214n-6 and n-3 polyunsaturated fats and, 363,

364fsynthesis of, 213–214, 215fTXA2, 213f, 214, 215f

production by activated platelets, 214Thymidine, 409f

salvage of, 304synthesis of, drug inhibiting, 374f

Thymidine monophosphate (TMP), synthesisof, 303–304, 304f, 374

Thymidylate synthase, 303Thymine, 291, 291f, 305f, 396f

damage to and repair of, 412pairing with adenine, 397, 397f, 398f

Thymine dimers, 412Tightly coupled reactions, electron transport

and oxidative phosphorylation, 78Tissues, use of dietary lipids by, 178Titration, of amino acids, 6f, 7–9, 8fTocopherol, α-, 391, 392fTolerable Upper Intake Level (UL), 358, 359fTophaceous gout, 299, 301fTophi, 299Trans-acting elements, 449–450, 450f

in eukaryotic transcription, 455Transaldolase, 147Transamination, of amino acids, 245, 250–252,

250f, 251fbranched-chain, 266equilibrium of reactions, 251

Transcortin, 237Transcription, 395, 417, 417f

concept map, 429feukaryotic, 422–424

combinatorial control of, 455, 455fenhancers in, 424, 424fpromoters in, 422–423, 423fregulation of, 449f, 454–461

prokaryotic, 419–421antibiotics targeting, 421, 422felongation in, 420–421, 420fhairpin turn in, 421, 421finitiation of, 419–420, 420fregulation of, 449f, 450–454termination of, 421, 421f

regulation of, 449–450Transcription factors, 422–423, 423f, 449Transcription unit, 419Trans fatty acids, 363–364, 363fTransfection, 467

Transferases, 53fTransferrin receptor (TfR), synthesis of,

458–459, 458fTransfer RNA (tRNA), 418, 418f

as adaptor molecules, 435anticodon of, 435antiparallel binding with codon, 437, 437fattachment of amino acids to


codon recognition by, 435initiator, 438, 440fposttranscriptional modification of, 425,

425fin protein synthesis, 435ribosomal binding sites for, 436synthesis of, 425unusual bases of, 417f, 418, 425

Transformation, 467Transformylase, 439Transgenic animals, 486Transition state, in enzyme-catalyzed

reactions, 55f, 56stabilization of, active site and, 56visualization of, 56, 56f

Transketolase, 146f, 147, 379fTranslation, of mRNA, 431–443, 431f, 460,

460fcomponents required for, 434–437initiation of, 438–439, 440fsteps in, 438–442, 440–441f

Translocation, 439Transmissible spongiform encephalopathies

(TSEs), 22Transposons (Tn), 408, 461Trehalase, 87Trehalose, 87Treponema pallidum, 202Tretinoin, 385, 385fTriacylglycerol (TAG), 173, 173f

in absorptive/fed state, 321in adipocytes, 350in chylomicrons, 228–231, 229f, 232fdegradation of, 92f, 175, 181f, 199f

in absorptive/fed state, 325in fasting, 331, 331fhormone regulation of, 190, 190finsulin and, 311by lipoprotein lipase, 228–229

in diabetes mellitustype 1, 339, 339fin type 2, 344, 345f

dietary, 361–364coronary heart disease and, 360–361,

361felevated levels of, 228–229, 339f, 340,

344, 345femulsification of, 175, 224in fasting, 329, 331, 331ffates of, in liver vs. adipose tissue, 189fatty acid component of, 181–183, 188–189

release of, 189–190, 190finsulin and, 189, 190fmetabolism of, 173–178, 180fniacin and, 380in obesity, 353in plasma lipoproteins, 227, 227fprocessing in stomach, 173–174, 174fresynthesis of, 176–177secretion from enterocytes, 177, 177fstorage of, 188–189stored, mobilization of, 189–195structure of, 188, 188fsynthesis of, 92f, 181f, 188–189, 188f,

189f, 199fin absorptive/fed state, 324, 325, 325f

transfer from VLDL to HDL, 231, 231fuse by tissues, 178

Tricarboxylic acid (TCA) cycle, 92f, 93,109–116, 109f

as aerobic pathway, 109ATP production in, 109, 113, 113f, 114fconcept map, 115fenergy produced by, 113–114, 113ffunction of, 107, 115fintermediates of, amino acid catabolism

yieldingrate limiting steps of, 112reactions of, 109–113regulation of, 114, 114f, 115f

by activation and inhibition of enzymeactivities, 114, 114f

by availability of ADP, 114Trimethoprim, 293

tetrahydrofolate synthesis inhibition by,374f

Trimming, 443, 443fTrinucleotide repeat expansion, 433, 433fTriose phosphate isomerase, 1011,4,5-Triphosphate (IP3), 205–206Triple helix, in collagen, 43f, 45, 46fTropocollagen, 47f, 48Tropomyosin (TM), 427, 457Troponin I and T, 66Trypanosomes, 206Trypsin, 16f, 443

inhibition of, 50in lipid digestion, 175pH optimum for, 58fin protein digestion, 248, 249f

Trypsinogen, 443Tryptophan

α-helix disrupted by, 17catabolism of, 266in serotonin synthesis, 287, 287fside chains of, 2f

Tryptophan hydroxylase, 271Tryptophan operon, 452–453, 453fTryptophan pyrrolase, 277TSEs. See Transmissible spongiform

encephalopathiesTTP, synthesis of, 460–461Tuberculosis, isoniazid for, 377f, 378Tunicamycin, 167Turnover number (kcat), 54Two-fold rotational symmetry, 466, 466fType 1 hyperlipoproteinemia, 229Type Ia glycogen storage disease, 121Type I DNA topoisomerases, 401, 401fType II DNA topoisomerases, 401, 401fType II hyperlipidemia, 232Tyrosinase-negative oculocutaneous albinism,

272, 272fTyrosinase (tyrosine hydroxylase)

in catecholamine synthesis, 285deficiency of, 271in phenylketonuria, 271

Tyrosine, 4, 4fcatabolism of, 263, 263f

disorder of, 263in catecholamine synthesis, 285, 286fin melanin synthesis, 288metabolic defect in albinism, 273phenylketonuria and, 272side chains of, 3f, 4synthesis of, 268, 270f

Tyrosine kinase, 312Tyrosinemia type I, 268f, 269f


Index 519

UUbiquinone. See Coenzyme QUbiquitin, 247, 444Ubiquitination, 444Ubiquitin-proteasome proteolytic pathway,

246–247, 247fUCP1 (thermogenin), 79UDP-galactose, 166

in biosynthetic reactions, 141as carbon source for

glycolysis/gluconeogenesis,140–141

formation of, 140, 141fstructure of, 141f

UDP-galactose:glucose galactosyltransferase,142

UDP-glucose, 166structure of, 127fsynthesis of, 126

UDP-glucose pyrophosphorylase, 126UDP-glucuronic acid, 161, 162fUDP-hexose 4-epimerase, 140, 141UDP-N-acetylgalactosamine, 166UDP-N-acetylglucosamine, 166Ultraviolet light, repair of damage caused by,

412, 412fUncharged polar amino acids, 3f, 4Uncoupling proteins (UCP), 79Upper body obesity, 350, 350fUpstream, 420Uracil, 291, 291f, 292f, 305f

in codons/genetic code, 431, 432fUrate oxidase, 298Urea, 253

ammonia disposal in, 253, 257, 257ffate of, 255

Urea cycle, 92f, 245f, 253–256ammonia disposal in, 253, 256–258deficiency in, 257–258, 258foverall stoichiometry of, 255–256reactions of, 253–255, 254fregulation of, 255f, 256

Urease, 255, 257Uric acid

conversion of dietary nucleic acids to, 298,299f

as end product of purine degradation,298–299, 300f

formation of, 298–299in gout, 299–301, 301fin Lesch-Nyhan syndrome, 296–297, 296f,

300overproduction of, 299–301underexcretion of, 299

Uridine diphosphate (UDP)galactose attached to, 140–141, 141fglucose attached to, 126, 127f

Uridine monophosphate synthase, 302–303Uridine monophosphate (UMP)

deoxy form of (dUMP), 302–303, 304fin pyrimidine synthesis, 302, 303f

Uridine triphosphate (UTP)in glycogen synthesis, 126, 127fsynthesis of, 303, 303f, 304f

Uridyltransferase, 141Urobilinogen, 283f, 284

in jaundice, 284Urobilins, formation in intestine, 283–284Urocanic acid, 262, 263fUrolithiasis, 298Uronic acid pathway, 161, 162fUronosyl 5-epimerase, 161Uroporphyrin, 277

Uroporphyrin I, 278, 278fUroporphyrin II, 278, 278fUroporphyrinogen, 279Uroporphyrinogen decarboxylase, deficiency

of, 280, 281fUroporphyrinogen III, 279fUroporphyrinogen III synthase, 281fUroporphyrinogen II synthase, 279UTP diphosphatase (dUTPase), 303uvrABC excinuclease, 412UV-specific endonuclease, 412

VValine, 265

in absorptive/fed state, 324α-helix disrupted by, 17catabolism of, 266–267, 266fglutamate replaced by, in sickle cell

disease, 36, 36fpeptide bond with alanine, 13, 14fside chains of, 2f

Valine therapy, for maple syrup urine disease,273

Valyalanine, 14, 14fValyglycylleucine, 14Vanadium, Dietary Reference Intakes for, 358fvan den Bergh reaction, 285Vanillylmandelic acid (VMA), 286Variable number of tandem repeats (VNTR),

475, 476fVariegate porphyria, 280, 281fVascular disease, homocysteine and, 263,

265, 265fVascular endothelial growth factor (VEGF),

459Vectors, 467–468

cloning, 468expression, 470, 470fprokaryotic plasmids, 467, 467f

Velocity, of enzymatic reactionscompetitive inhibition and, 60–61, 60fenzyme concentration and, 59factors affecting, 56–58hyperbolic kinetics curve of, 57, 57finitial, 57, 59maximal (Vmax), 57, 57fnoncompetitive inhibition and, 61–62, 61fpH and, 57–58, 58fsubstrate concentration and, 57, 57f,

58–59, 59ftemperature and, 57, 57f

Versican, 158Very-long-chain fatty acids (VLCFA), 187, 195Very-low-density lipoproteins (VLDLs), 189,

227, 227f, 228f, 231, 231f, 232fin absorptive/fed state, 323f, 324circulating, modification of, 231, 231fcomposition of, 232fconversion to low-density lipoprotein, in

plasma, 231in diabetes mellitus

type 1, 339–340, 339ftype 2, 344

electrophoretic mobility of, 227, 228fmetabolism of, 230f, 231niacin and, 380in obesity, 353release of, 230f, 231size and density of, 227, 227f

Vibrio cholerae, 94Vidarabine, 409Vision, vitamin A and, 382, 383f, 384Vitamin A, 373, 381–386, 392–393f

absorption of, 382, 383fclinical indications for, 384–385, 385fdeficiency of, 384–385, 385f, 393fdermatologic use of, 385, 385f, 386dietary intake of

cancer risk and, 391excessive, 375, 385–386requirement for, 358f, 384sources of, 383f, 384

distribution of, 384epithelial cells and, 384functions of, 382–384, 383f, 392fgrowth and, 384mechanism of action, 382, 383f, 384f, 385fprevention of chronic disease and,

384–385, 385freproduction and, 384storage of, 383fstructure of, 382, 382fsupplementation of, 384, 391toxicity of, 385–386, 393ftransport of, 382, 383fvision and, 382, 383f, 384

Vitamin B1. See ThiamineVitamin B2. See RiboflavinVitamin B6, 378, 392–393f

active form of, 377f, 378, 392fclinical indications for, 378cysteine synthesis and, 265deficiency of, 378, 393fdietary intake of

cardiovascular risk and, 265Dietary Reference Intakes for, 358f

function of, 392ffor homocystinuria, 273in homocystinuria, 273structure of, 377f, 378supplementation of, 391toxicity of, 378

Vitamin B12for homocystinuria, 273

Vitamin B12, 265, 375–377absorption of, 376f, 377active forms of, 375, 376f, 392fclinical indications for, 376–377as coenzyme, 375, 375f, 376f

in succinyl CoA synthesis, 194–195,195f

deficiency of, 375, 377, 393fanemia and, 374, 377folate trap hypothesis of, 376

dietary intake ofcardiovascular risk and, 265, 265fDietary Reference Intakes for, 358fsources of, 376

distribution of, 376function of, 392fin homocystinuria, 273megaloblastic anemia and, 375structure of, 375, 376fsupplementation of, 391synthesis of, 376

Vitamin B12 (deoxyadenosylcobalamin), 194Vitamin C, 377–378, 392–393f

active form of (ascorbic acid), 377, 377f,392f

as antioxidant, 148–149, 377–378, 391as coenzyme, 377collagen biosynthesis and, 47, 47f, 377deficiency of, 377, 377f, 393fdietary intake of

cancer risk and, 378, 391Dietary Reference Intakes for, 358f


function of, 377prevention of chronic disease and,

377–378structure of, 377, 377fsupplementation of, 391

Vitamin D, 373, 386–389, 392–393fbone action of, 388calcium and, 386, 388, 388fcholesterol as precursor of, 219clinical indications for, 388–389deficiency of, 388–389, 389f, 393fdietary intake of

Dietary Reference Intakes for, 358fexcessive, 373, 389sources of, 386

distribution of, 386, 388endogenous precursor of, 386function of, 387f, 388, 392fhydroxylation of, 149intestinal action of, 388metabolism of, 386–388, 387f

regulation of, 386–388supplementation of, 391toxicity of, 389, 393fin transcriptional regulation, 456

Vitamin E, 148, 391, 392–393factive form of, 392fas antioxidant, 148–149, 377, 391clinical indications for, 391deficiency of, 391, 393fdietary intake of

cancer risk and, 391Dietary Reference Intakes for, 358frequirement for, 391sources of, 391

distribution of, 391function of, 391, 392fstructure of, 391, 391fsupplementation of, 391

toxicity, 391, 393fVitamin K, 373, 389–391, 392–393f

blood coagulation and, 389, 390fclinical indications for, 390deficiency of, 390, 393f

in newborn, 390dietary intake of

requirement for, 358f, 390sources of, 390

distribution of, 390in formation of γ-carboxyglutamate, 389,

389ffunction of, 389–390, 392ftoxicity of, 391, 393f

Vitamin K-dependent carboxylation, 444Vitamin(s), 373–394, 392–393f

classification of, 373, 373fcoenzymes and, 54fat-soluble, 373, 373f, 392–393fsupplements of, 391water-soluble, 373, 373f, 392–393f

VLDL. See Very-low-density lipoproteinsvon Gierke disease, 130f, 301

WWaist to hip ratio in obesity, 349Waist size in obesity, 349Warfarin, 389Water-soluble vitamins, 373, 373f, 392–393fWeight. See Body weight, Obesity

Wernicke-Korsakoff syndrome,110, 379, 393f

Western blot, 473, 484, 485fWestern diet, 362fWhite blood cells

as DNA source, 476phagocytosis by, 150, 150f

Wilson disease, 48

Wobble hypothesis, 437, 437fWolman disease, 232

XXanthine, 299Xanthine oxidase, 299, 300f, 301Xenobiotics, 149Xeroderma pigmentosum, 412, 412fXerophthalmia, 384–385, 393fX-linked adrenoleukodystrophy, 195X-linked sideroblastic anemia, 278X-linked severe combined immunodeficiency

(SCID-X), 485Xylosyltransferase, 162D-Xylulose 5-phosphate, 161

YYeast artificial chromosomes (YACs), 468

ZZ-DNA, 398, 399f, 460Zellweger syndrome, 195Zero-order reactions, 59, 59fZidovudine (AZT), 409, 409fZinc, Dietary Reference Intakes for, 358fZinc finger motif, 18, 423, 450, 450fZwitterion, 7, 7fZymogens, 64, 443

activation of, 248gastric, 248pancreatic, 248, 249fin protein digestion, 248

520

Figure Sources

Figure 2.12: Modified from Garrett, R. H. andGrisham, C. M. Biochemistry. SaundersCollege Publishing, 1995. Figure 6.36, p. 193.Figure 2.13 (panel C, top): Abdulla, S.Basic mechanisms of protein folding disease.Nature Publishing Group. Figure 3.1A: Illustration: Irving Geis. Rightsowned by Howard Hughes Medical Institute.Not to be used without permissionFigure 3.20: Photo curtesy of PhotodyneIncorporated, Hartland, WI.Figure 3.21: CorbisFigure 4.3: Electron micrograph of collagen:Natural Toxin Research Center. Texas A&MUniversity-Kingsville. Collagen moleculemodified from Mathews, C. K., van Holde, K.E. and Ahern, K. G. Biochemistry. 3rd Ed.,Addison Wesley Longman, Inc. 2000. Figure6.13, p.175.Figure 4.4: modified from Yurchenco, P. D.,Birk, D. E., and Mecham, R. P., eds. (1994)Extracellular Matrix Assembly and Structure,Academic Press, San Diego, CaliforniaFigure 4.8: Kronauer and Buhler, Images inClinical Medicine, The New England Journalof Medicine, June 15, 1995 , Vol. 332, No. 24,p.1611.Figure 4.10: Photo from Web site Derma.deFigure 4.11: Jorde, L. B., Carey, J. C.,

Bamshad, M. J. and White, R. L. MedicalGenetics, 2nd Ed.http://medgen.genetics.utah.edu/index.htmQuestion 4.3: from Berge LN, Marton V,Tranebjaerg L, Kearney MS, Kiserud T, OianP. Prenatal diagnosis of osteogenesisimperfecta. Acta Obstetricia et GynecologicaScandinavica. 74(4):321-3, 1995 Apr.Figure 13.11: The Crookston Collection,University of Toronto.Figure 17.13: Urbana Atlas of Pathology,University of Illinois College of Medicine aturbana-champaign. Image number 26.Figure 17.19: Interactive Case StudyCompanion to Robbins Pathologic Basis ofDisease.Figure 18.12: Custom Medical Stock Photo.Figure 20.20: Success in MRCO phth.http://www.mrcophth.com/iriscases/albinism.htmlFigure 20.22 (top): Rubin, E. and Farber, J.L. Pathology (2nd edition). J. B. Lippinoctt.194.Figure 6-30, p. 244.Figure 20.22 (bottom): Gilbert-Barness, E.and Barness L. Metabolic Disease. EatonPublishing, 2000. Figure 15, p.42.Figure 21.6: Rich, M. W. Porphyria cutaneatarda, Post graduate Medicine, 105: 208-214(1999).

Figure 21.5: Department of Dermatlogy,University of Pittsburgh.http://www.upmc.edu/dermatology/MedStudentInfo/introLecture/enlarged/vespct.htm.Figure 21.10: Custom Medical Stock Photo,Inc.Figure 21.13: Phototake.Figure 22.16: Wuthrich, D. A., and Lebowitz.Tophaceous gout. Images in clinical Medicine.N Engl J Med, 332:646, 1995.Figure 22.17: WebMD Inc.http://www.samed.com/sam/forms/index.htmFigure 22.18 : Corbis.Figure 23.2: Childs, G.http://www.cytochemistry.net/.Figure 24.4: Phototake.Figure 26.6: Corbis.Figure 27.20: Joseph E. ArmstrongIllinois State University.Figure 28.4: Matthews, J. H. Queen’sUniversity Department of Medicine, Division ofHematology/Oncology, Kingston, Canada.Figure 29.7: Nolan, J., Department ofBiochemistry, Tulane University, New Orleans,LA.Figure 23.13: Modified from Cryer, P. E.,Fisher, J. N. and Shamoon, H. Hypoglycemia.Diabetes Care 17:734-753, 1994.


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