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Navigating Metabolism This is a free sample of content from Navigating Metabolism. Click here for more information on how to buy the book. Index Page references followed by b denote boxes; those followed by f denote figures; those followed by t denote tables. A Acyl-CoA synthetase, 110 Acyl transacylase, 107, 109f ACC (acetyl-CoA carboxylase), 105, 107, Adenine, 148, 149f, 155, 157f. 109f, 113, 115, 117, 173 See also Purines Acetate, 182, 193 Adenine nucleotide transporter (ANT), 38, Acetoacetate, 116b, 117b 47f, 53, 56–57 Acetone, 116b, 117b Adenosine, 142, 143f, 164–165, 164f Acetylation, 181–183, 184f Adenosine deaminase, 165 acetyl-CoA and, 9, 10f, 181–183, 184f Adenosine phosphoribosyltransferase (APRT), of lysine residues, 2, 183 155, 157f Acetyl-CoA, 2 Adenylate kinase, 16, 32, 112, 152, 154f allosteric regulation of pyruvate Adenylosuccinate, 152, 154f–155f carboxylase, 93 ADP from citrate, 43, 53, 56f, 59, 60f, 71, 72f, adenine nucleotide transporter (ANT), 38, 47f, 107, 108f 53, 56–57 citrate transporter and, 53–54, 56f adenylate kinase reaction, 16, 32, 112 entry into TCA cycle, 41, 42f energy charge, 18 in fatty acid synthesis, 107–110, 108f–109f P2 purinoreceptor activation, generation of, 39, 41, 42f, 43, 45, 45f, 164, 164f 53–54, 56f, 59 Aerobic glycolysis, 34–35, 190, 220 metabolic functions, 9, 10f, 53 Aging posttranslational modifications and, free radical theory of, 83b 181–183, 184f metabolism and, 212 Acetyl-CoA carboxylase (ACC), 105, 107, AKT, 120, 168f, 169–170, 199 109f, 113, 115, 117, 173 Alanine Acetylserotonin O-methyltransferase, β-alanine, 161–162, 163f 139, 140f conversion to pyruvate, 93 Aconitase, 60, 70 generation of, 130, 132f Activation energy, 13, 13f, 18 from pyruvate, 26 Active site, 20 urea cycle and, 134 Acyclglycerophosphate acyltransferase, 110, 111f Alanine aminotransferase, 134 ACYL (ATP-citrate lyase), 53, 56f, 59, 71, Albinism, 41 72f, 107, 108f, 182, 192 Alcohol dehydrogenase, 31f 233 © 2015 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Navigating Metabolism. Click here for more information on how to buy the book. 234 Index Aldolase B, 100, 101f fatty acid regulation, 117 Aldosterone, 121, 122f metformin and, 2, 209b Allopurinol, 156f, 157b nutrient sensing, 216–217 Allosteric enzymes, 20 salicylate inactivation of, 120 Allosteric regulation, 26, 27f, 32, 45, 93 SIRT1 phosphorylation by, 184 Allosteric site, 20, 21 Amphibolic pathway, 41 α-ketoglutarate Amylo-(1,4–1,6)-transglycosylase, 96 amino acid generation from, 130, 132f, 134 Anabolism from cystathionine, 142, 143f aberrant activation of signaling pathways in from glutaminolysis, 39, 44, 44f, 45, 59, 94–95 proliferating cells, 197–203, isocitrate conversion to, 70, 71f 198f–199f, 201f in TCA cycle, 39, 42f–45f, 43–45, 59–60, 60f acetyl-CoA role in, 10f α-ketoglutarate dehydrogenase, 41, 42f, 45, 45f, 77 entropy change in anabolic reactions, 11 α-ketoglutarate-dependent dioxygenase family, overview, 1, 2f, 9 4–5, 177, 186, 203, 221 Anaerobic glycolysis, 31 α-proteobacteria Analyzing metabolism, 223–231 endosymbiont theory and, 37 Anaplerosis, 43–44 proton pumps, 47 Anemia, 68, 70b Amino acids, 127–145 Angiogenesis, 202 arginine metabolism, 129, 144, 145f ANT (adenine nucleotide transporter), 38, 47f, 53, conversion to TCA cycle intermediates, 132, 56–57 133f Antimetabolite drug, 206 cysteine production, 142, 143f, 144 Antioxidants, 207, 209 degradation, 131–136, 133f, 135f, 137f Antiporters, 58 epigenetics and, 142 Apoptosis, 58 essential, 127, 128f, 129 APRT (adenosine phosphoribosyltransferase), feeding into TCA cycle, 39 155, 157f methionine metabolism, 128, 142–144, 143f Archaea for neurotransmission, 138–140, 139f–141f endosymbiont theory and, 37 overview of metabolism, 128f proton pumps, 47 production of nonessential, 129–131, 130f–132f Arginase, 134, 137f quick guide, 127–129, 128f Arginine tryptophan metabolism, 129 L-arginine, 144, 145f tyrosine metabolism, 128, 129, 139–142, 141f nitric oxide production, 144, 145f 4-Aminobutyrate aminotransferase, 138, 139f in urea cycle, 129, 134, 136b, 137f Amino sugars, 26, 27f Arginosuccinase, 134, 137f Ammonium ions, 128, 130, 131, 132f–133f, 134 Arginosuccinate, 134, 137f AMP Arginosuccinate synthetase, 134, 137f from adenine, 156, 157f Artificial sweeteners, 101b cAMP, 95, 97b, 162 Asparagine, 130 catabolism, 152, 156f Asparagine synthetase, 130, 132f energy charge, 18 Aspartate, 43, 44f increasing levels of, 16, 32, 45, 61, 95, 156, 172 in pyrimidine biosynthesis, 158, 159f from inosine 50-monophosphate, 152, 154f urea cycle and, 134, 135f, 136, 137f PFK1 regulation, 32 Aspartate aminotransferase, 130, 132f, 134 regulation of gluconeogenesis, 95, 96f Aspartate transcarboylase, 158 AMP-activated protein kinase (AMPK) Aspirin, 2 activation of, 16, 172–173, 173f, 181 Atkinson, Daniel, 18 autophagy regulation, 177 ATM, 218 in cancer cells, 200 ATP, 9, 11 catabolism induction by, 61, 172–173, adenine nucleotide transporter (ANT), 38, 47f, 173f–174f 53, 56–57 cholesterol regulation, 121, 123 allosteric regulation of TCA cycle, 45 © 2015 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Navigating Metabolism. Click here for more information on how to buy the book. Index 235 amount generated by complete oxidation of 2,3-Bisphosphoglycerate, 25f, 26, 27f glucose, 54–55, 57f Body mass index (BMI), 103 discovery of, 24b Bond energy, 11, 12, 14 energy charge, 18 Branching enzyme, 96, 98f extracellularas signaling molecule, 162, 164, 164f Breast cancer, 100, 205 generation Brown, Michael, 124–125 in amino acid degradation, 132, 134 Brown fat cells, uncoupled respiration in, 49 in cancer cells, 198, 202 Butyric acid, 105, 106f in glycolysis, 23, 24, 25f, 26 in lipid catabolism, 111–113 C in NADH and FADH2 oxidation, 51 in proliferating cells, 193 Caffeine, 165b – oxidative phosphorylation, 38, 39, 46 51, 47f Calcium production by adenylate kinase, 16, 32 AMP-activated protein kinase (AMPK) – production in mitochondria, 23, 26, 38 39, 41 activation, 173, 173f – for proliferating cell metabolic needs, 189 190, homeostasis regulation by mitochondria, 57–58, 189f 59f – respiratory rate controlled by, 55 57 stimulation of TCA cycle by, 45–46, 45f uncoupling biosynthetic activity from ATP Calorie, 11 – generation in mitochondria, 58 60, 60f cAMP, 95, 97b, 162 use in glycolysis, 29 cAMP-dependent protein kinase A (PKA), 95, 97b ATP-citrate lyase (ACLY), 53, 56f, 59, 71, 72f, Cancer. See also Cancer metabolism 107, 108f, 182, 192 aberrant activation of signaling pathways, – ATP-coupled reaction, 15 16, 15f 197–203, 198f–199f, 201f ATP synthase, 39, 46, 47f, 49 breast, 100, 205 Autoimmunity, 215 genetic alterations driving tumorigenesis, – Autophagosome, 175 176, 175f 203–206, 204f – – Autophagy, 167, 174 177, 175f 176f glucose metabolism in cancer cells, 34–35, 34f hyaluronic acid expression in breast cancer stem B cells, 100 hypoxia and, 202–203 Beclin 1 interacting complex, 175–176, 176f metabolic plasticity, 206 Beer, 31 metformin as anticancer agent, 208b–209b, 208f β-alanine, 161–162, 163f non-small cell lung cancer, 206 β-aminoisobutyrate, 161–162, 163f prostate, 231 β-hydroxybutyrate, 116b, 117b therapeutic targets, 206–209, 220–221 Betaine-homocysteine S-methyl transferase, 142, Warburg effect, 190, 231 143f Cancer metabolism, 4–5 β-ketoacyl carrier protein reductase, 107, 109f fructose metabolism by tumor cells, 100b β-ketoacyl synthase, 107, 109f future perspectives, 213–214 β-oxidation, 103, 105, 111, 113, 114f glucose metabolism, 34–35, 34f Bicarbonate, 90 heterogeneity of, 197, 199, 206 Bile acid, 121 modern understanding of, 219–220 Biochemistry, defined, 7 oncometabolites, 226 Biosynthesis one-carbon metabolism, 73, 205 biosynthetic capacity of glycolytic rebirth of, 218–219 intermediates, 24, 26, 27f, 29, 32, 35 as therapeutic target, 206–209, 220–221 NADPH and, 65, 66 Carbamoyl phosphate, 134, 135f, 137f, 158, 159f TCA cycle as biosynthetic hub, 42–44, 43f Carbamoyl phosphate synthetase I, 134, 137f uncoupling biosynthetic activity from ATP Carbamoyl phosphate synthetase II, 158, 160, 162f generation in mitochondria, 58–60, 60f Carbohydrate response elements, 180–181, 180f Biotin, 90 Carbohydrates, 85–101 1,3-Bisphosphoglycerate, 25f, 26, 27f, 29, 93 complex, 85 © 2015 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Navigating Metabolism. Click here for more information on how to buy the book. 236 Index Carbohydrates (Continued) generation by glutamine-dependent reductive metabolism of simple sugars, 87–90, 87f–89f carboxylation, 60, 60f overview of metabolism, 86f from glutamine-dependent reductive quick guide to, 85, 87 carboxylation, 203 signaling and, 87, 97–100 in TCA cycle, 39, 41, 42f, 43, 43f, 45 Carbon transport into cytosol, 43, 53–54, 54f, 59, 107, carbon substrate, cell choice of, 213 108f, 192 isotope tracing, 227–231, 228f Citrate synthase, 41, 42f, 45, 45f Carbon dioxide, release in TCA cycle, 41, 42f, 55 Citrate transporter, 53–54, 54f Carbonyl cyanide-p-trifluoromethoxyphenyl- Citric acid cycle. See TCA cycle hydrazone (FCCP), 49, 50b, 58 Citrulline, 134, 136b, 137f, 144, 145f Carnitine-acylcarnitine translocase, 103, 112f, 113 Coenzymes, 19 Carnitine acyltransferase I (CPTI), 103, 105, 112f, Cofactors, 19 113, 117 Common cold, 82 Carnitine acyltransferase II (CPTII), 103, 112f, 113 Competitive inhibition, 20, 21f Carnitine transport cycle, 103, 112f, 113 Concentration, affect on reaction rate, 19–20, 20f Catabolism Conservation
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