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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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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
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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
in glycosaminoglycans, 157, 157f, 160,161f
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
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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
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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
communication with other metabolicorgans, 307, 307f
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
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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
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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
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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
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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
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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
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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
anatomical differences in, 350, 350fbiochemical differences in, 350
depot, 189dietary, 360–365
acceptable distribution ranges for, 360,360f
coronary heart disease and, 360–361,361f
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
coronary heart disease and, 360–361,361f
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
absorption by intestinal mucosal cells,176
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
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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
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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
absorption by intestinal mucosal cells,87
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
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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
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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
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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
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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
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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
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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 branched-chain α-ketoaciddehydrogenase, 266
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
acceptable distribution ranges for, 360,360f
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
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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
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Mucopolysaccharides, 157. See alsoGlycosaminoglycans
Mucopolysaccharidoses, 163, 164fMultiple carboxylase deficiency, 381Muscle(s)
cardiaccarnitine deficiency in, 192lipoprotein lipase in, 228myoglobin in, 26skeletal vs., 326
communication with other metabolicorgans, 307, 307f
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 branched-chain α-ketoaciddehydrogenase, 266
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
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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
anatomical differences in, 350, 350fbiochemical differences in, 350
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
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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
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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
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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
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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
acceptable distribution ranges for, 360,360f
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
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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
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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
enzymes required for, 435, 435fsite for, 434f, 435
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
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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
in glycosaminoglycans, 157, 157f, 160,161f
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
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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
enzymes required for, 435, 435fsite for, 434f, 435
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
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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
168397_P489-520.qxd7.0:34 Index 6-2-04 26p 2010.4.5 10:03 AM Page 519
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
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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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