Index

Page numbers in bold denote tables.

AANAT see arylalkylamine N‐acetyltransferase adrenal leucodystrophy protein (ALDP) 79 antimycin A 7 ABCC8, β‐cell KATP channel gene mutation 120 see also ABCD1 transporter and X-ALD antipurines, mechanisms 110 ABCD1 transporter and X-ALD 78 adrenaline 98 antipyrimidines, mechanisms 110 ABCD3 transporter 78 biosynthesis 99, 108 arachidic acid 78 acetaldehyde, metabolism 48 fight or flight response 20, 22, 26 arachidonic acid, as eicosanoid hormone precursor 68, 78 acetoacetate 66, 118 glycogenolysis stimulation 22, 24, 25, 26, 27 arachidonoyl CoA, biosynthesis 68 in ketogenesis 72, 73, 74, 75, 90, 91 glycolysis stimulation 14, 32, 34 arginase 103, 105 acetoacetyl CoA, biosynthesis 72, 73 lipolysis stimulation 60, 61 arginine 88 acetoacetyl CoA thiolase, catalysis 72, 73, 74, 75 phaeochromocytoma 98 biosynthesis 102, 104 acetone 72, 73 adrenoleukodystrophy, X‐linked, aetiology of 78–9 catabolism 92 acetylcholine, insulin secretion stimulation 120, 121 aerobic ATP synthesis 10–13, 18, 19, 34, 35 argininosuccinate, biosynthesis in urea cycle 102, 105 acetyl CoA affective disorders argininosuccinate synthetase 105 biosynthesis 40, 43, 54, 72, 92 aetiology 100 argininosuccinic aciduria 117 gluconeogenesis in fasting 94 amine hypothesis 100 aromatase inhibitors 87 in ketogenesis 72 AICAR and rheumatoid arthritis 110 arylalkylamine N-acetyltransferase (AANAT) 100 oxidation 40 AICARiboside and rheumatoid arthritis 110 ASase (adenylosuccinase) deficiency 39, 109, 113 pyruvate dehydrogenase inhibition 36, 38, 39, 56, 94 A-kinase anchoring protein 26 ascorbate, biosynthesis 44 roles 50, 66 Akt see protein kinase B (PKB) asparagine, biosynthesis 88 acetyl CoA carboxylase 52, 56 ALA see 5‐aminolevulinic acid (ALA) aspartate activation 54 alanine biosynthesis 88, 102 N‐acetylglutamate (NAG), biosynthesis 102 biosynthesis in diabetes 90, 122, 123 malate/aspartate shuttle 9 N‐acetylglutamate synthase, catalysis 102 from muscle 90 and purine biosynthesis 108 acetyl 38 catabolism 92 and purine nucleotide cycle 39 ackee fruit 71 as gluconeogenic precursor 36 aspartate aminotransferase (AST), malate/aspartate shuttle 9 ACP (acyl carrier protein) 54, 106 glucose alanine cycle 90, 91 and urea cycle 102, 103 acyl carrier protein (ACP), roles, in fatty acid biosynthesis 54, 106 pyruvate kinase inhibition 32 aspirin, and Reye’s syndrome 116, 117 acyl CoA dehydrogenases 70, 71, 76, 77 alanine cycle (glucose alanine cycle) 90, 91 AST see aspartate aminotransferase (AST) localization 70 albinism, aetiology 96 atorvastatin 85 acyl CoA esters, transport 60 alcohol, metabolism 48–9 ATP see adenosine triphosphate (ATP) acyl CoA oxidase, catalysis 78, 79 alcohol dehydrogenase, roles, in ethanol metabolism 15, 48, 49 ATP/ADP 4 acyltransferase 56 alcoholic fermentation 15 inhibition 7 adenosine alcoholism, treatment 48 ATP synthetase 7 accumulation following AICAR 110 ALD (adrenoleukodystrophy) 78–9 ATP synthetase complex 6 biosynthesis 34 aldehyde dehydrogenase, deficiency 48 atractyloside 7 adenosine diphosphate (ADP), phosphorylation 4 aldolase, deficiency 16, atrial natriuretic factor 60 adenosine monophosphate (AMP) aldolase A 25, 31, 45, 46, 47 axons 74 biosynthesis 18 aldolase B 46, 47 azaserine, inhibitory activity 110 fatty acid oxidation 18, 19, 70, 71 aldose reductase azide, electron transport inhibition 7 phosphorylation 4 catalysis 44, 45 azidothymidine (AZT), phosphorylation 110 see also cyclic AMP in diabetes mellitus 44, 45 azidothymidine triphosphate (AZTTP), inhibitory activity 110 adenosine monophosphate deaminase, deficiency 38 inhibitors 44 AZT (azidothymidine), phosphorylation 110 adenosine triphosphate (ATP) 2, 4, 10 aldosterone, biosynthesis 86, 87 AZTTP (azidothymidine triphosphate), inhibitory activity 110 aerobic, production 34, 35 ALDP see adrenal leucodystrophy protein (ALDP) anaerobic, production, 34 alkaptonuria, aetiology 96, 97 Bai and Paik shunt 84 biosynthesis 4–7, 12–13 allantoin 112 barbiturates in glucose metabolism 14 amine hypothesis 100 potentiation of ALA synthase 114 d‐3‐hydroxybutyrate oxidation 74 aminoacetone pathway for threonine metabolism 92 interaction with ethanol 48 β‐oxidation 18, 19 see also chart, back cover BCAAs see branched‐chain amino acids (BCAAs) phosphoanhydride bonds 4 amino acids BCKADH (α‐ketoacid dehydrogenase) 90 phosphofructokinase‐1 inhibition 30 branched‐chain 90 behenic acid 78 structure 4 catabolism 90–3 betaine, and homocysteine metabolism 109 as substrate 4 in diabetes 118 bicarbonate ion, 14C‐labelled and metabolic channelling 104, 105 S‐adenosylmethionine (SAM) 92 glucogenic 94–5 bifunctional PFK‐2/F2,6 bisPase 32, 33 biosynthesis 92, 93 in ketogenesis 72, 90 bile acids/salts 84, 86–7 as methyl donor 108 ketogenic 90 biosynthesis 86 adenylate cyclase, activation 26 metabolism disorders 96–7 bilirubin adenylate kinase, catalysis 34 non‐essential, biosynthesis 88–9 biosynthesis 114 adenylosuccinase (ASase) 108, 109, 113 in purine and pyrimidine biosynthesis 108, 109, 110–11 glucuronate conjugates 44 deficiency 39 COPYRIGHTEDin urea biosynthesis 50, 51, 92, 93 MATERIAL biliverdin, biosynthesis 114 adipic acid (hexanedioic acid) 70 see also individual amino acids biological clock 100 adipocytes aminoimidazole‐carboxamide ribonucleoside see AICAR and rheumatoid biotin, as 52 fatty acids 62, 63 arthritis bipolar disease, amine hypothesis 100 fructose transport 46 5‐aminolevulinic acid (ALA) 99 1,3‐bisphosphoglycerate, reduction 45 glucose transport 32, 64, 118 biosynthesis 114, 115 2,3‐bisphosphoglycerate (2,3‐BPG) 16–17 glycerol kinase expression 62 structural resemblance to succinyl acetone 99 adaptation to high altitude 16 insulin receptors 32 5‐aminolevulinic acid synthase, catalysis 114 importance in medicine 16 lipolysis 122 aminopterin 109, 111 bisphosphoglycerate mutase, deficiency 16 lipoprotein 59 aminotransferase, transamination 102 2,3‐bisphosphoglycerate (2,3-BPG phosphatase) triacylglycerol biosynthesis 52 ammonia 16, 17 adipose triacylglycerol lipase (ATGL) 60 biosynthesis 66 deficiency 16 regulation of 60 incorporation into glutamine 102 2,3‐bisphosphoglycerate shunt 16 adipose tissue ammonium chloride 104 Bloch pathway 84 brown 7, 64 ammonium ions 102, 112 blood glucose fatty acid mobilization 34, 60–3 ammonotelism 112 during fasting (gluconeogenesis) 90 free fatty acids 40 AMP see adenosine monophosphate (AMP) in type 2 diabetes (glyceroneogenesis) 64 glyceroneogenesis 64 AMP-dependent protein kinase 60 blood transfusions, and 2,3‐BPG 16 hormone‐sensitive lipase 18, 60, 61 amytal, electron transport inhibition 7 bombesin, insulin secretion stimulation 121 lipogenesis 30 anaerobic ATP synthesis 34 bongkrekic acid 7 lipolysis 60–3 anaerobic glycolysis 14–15, 22 2,3‐BPG see 2,3‐bisphosphoglycerate (2,3‐BPG) pentose phosphate pathway in 30 anaplerotic reactions 34, 38, 43 brain pyruvate dehydrogenase phosphatase in 38 anastrozole, aromatase inhibitor and breast cancer 87 fuel requirements 10, 20, 36, 40 thermogenesis 64 androstane 84 kernicterus 44 triacylglycerol biosynthesis 52 androstenedione, biosynthesis 87 branched‐chain amino acids (BCAAs), catabolism 90, 96 triacylglycerol storage 18 Antabuse, in alcoholism treatment 48 branched‐chain α‐ketoacid dehydrogenase (BCKADH), activity 96 white 5, 59, 60, 61, 62 antidiabetic drugs, glitazones 64 branched‐chain fatty acids 80 ADP see adenosine diphosphate (ADP) antimetabolites 110 branching enzyme, catalysis 3, 119

Metabolism at a Glance, Fourth Edition. J. G. Salway. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd. 125

0002858194.indd 125 11/26/2016 10:23:31 AM brown adipose tissue 64 clupanodonic acid 78 Δ4-desaturation of fatty acids 68, 69 thermogenesis 64 cofactors 10 14‐desmethyllanosterol 84 biotin 52 desmolase, catalysis 86, 87 calcium channels, voltage‐dependent 120 pyruvate dehydrogenase reaction 10 desmosterol, biosynthesis 85 calmodulin‐dependent protein kinase‐2, activation 120 vitamins as 10 desmosterolosis, aetiology 84 cancer comparative gene identification 58 (CGI-58) 60 dexamethasone, effect on PEPCK 64 chemotherapy 110 complexes I–IV 6 dGTP (deoxyguanosine triphosphate), biosynthesis 108 photodynamic therapy 114 proton transport 7 DHA (docosahexaenoic acid) 78 capric acid 78 COMT (catechol‐O‐methyltransferase) 99 DHF (dihydrofolate) 110 caproic acid 78 congenital adrenal hyperplasia 87 DHT (dihydrotestosterone) 86, 87 caprylic acid 78 congenital erythropoietic porphyria 115 diabetes mellitus carbamoyl aspartate, biosynthesis 103 coproporphyria, hereditary, aetiology 115 aetiology 10 carbamoyl phosphate 93, 95, 97, 102, 105 coproporphyrinogens, biosynthesis 115 antidiabetic drugs accumulation 103 core protein of fatty acid synthase 106 glitazones and glyceroneogenesis 56 biosynthesis (CPS) 102 Cori cycle glucokinase activators as candidate drugs 64 biosynthesis (CPS II) 111 muscle/liver 14 cataracts 44 carbamoyl phosphate synthetase (CPS) 102, 103, 105 red blood cells/liver 14 glucagonocentric diabetes 118, 122 carbamoyl phosphate synthetase II (CPS II), catalysis 110 Cori’s disease, aetiology 22 ketone body detection 72 carbohydrate response element binding protein see ChREBP cortisol maturity‐onset of young (MODY) 120 carbon monoxide, electron transport inhibition 7 biosynthesis 86, 87 metabolic processes in 118–19 carbonylcyanide‐p‐trifluoromethoxyphenylhydrazone (FCCP), protein effect on PEPCK 64 neonatal 120 transport inhibition 7 starvation and HSL 60 and sorbitol 44 carcinoid syndrome 100 cot death see sudden infant death syndrome (SIDS) see also type 1 diabetes; type 2 diabetes carcinoma of the liver in tyrosinaemia 98 C peptide 121 diacylglycerol (DAG) 58 cardiac muscle CPS see carbamoyl phosphate synthetase (CPS) diazoxide, insulin secretion inhibition 121 glycolysis 33 CPS II (carbamoyl phosphate synthetase II) 110 diazo‐oxo‐norleucin (DON), inhibitory activity 110 phosphofructokinase-2/fructose 2,6‐bisphosphatase 32 CPTs (carnitine‐palmitoyl ) 70 dicarboxylate carrier 2 cardiomyocytes, insulin sensitivity 32 creatine, biosynthesis 102, 103 dicarboxylic acids cardiovascular disease creatine phosphate, biosynthesis 103 biosynthesis on MCAD deficiency 70, 71 and cholesterol 84 Crigler–Najjar syndrome, aetiology 44 fatty 80 and homocysteine 108 crotonic acid 78 Krebs cycle, arguably ‘the dicarboxylic acid cycle’ 38, 92 caries see dental decay CTP (cytidine triphosphate) 110 dicarboxylic fatty acids oxidation 78 carnitine/acylcarnitine translocase, in carnitine shuttle 70, 71 cyanide, electron transport inhibition 7 dicyclohexylcarbodiimide (DCCD), proton transport inhibition 7 carnitine deficiency 70 cyclic AMP 25, 120 Δ3,5-Δ2,4-dienoyl CoA 78 carnitine‐palmitoyl transferases (CPTs) 70 binding to receptor 26 2,4‐dienoyl CoA reductase, catalysis 76, 77, 78, 79 carnitine shuttle 70–1, 76 biosynthesis 25, 26, 32 dihomo-γ-linolenic acid, as eicosanoid hormone precursor 68 casein kinases, glycogen synthase phosphorylation 28 removal 28 dihomo-γ-linolenoyl CoA, desaturation 68 catalase cyclic AMP‐dependent protein kinase see protein kinase A (PKA) dihydrofolate (DHF) 110 ethanol oxidation 48 cyclic AMP -3, activation 61 dihydrofolate reductase, catalysis 110 fatty acid oxidation 78 cyclic AMP phosphodiesterase-3B (PDE-3B) 28 24,25‐dihydrolanosterol 84 cataracts, diabetic, polyol osmotic theory 44 activation 27, 29 dihydrolipoyl dehydrogenase 38 catecholamines and lipolysis 60 CYP family dihydropyridine (DHP), calcium channel opening 121 biosynthesis 98 melatonin catabolism 100 dihydrotestosterone (DHT) 86 see also adrenaline ω-oxidation of fatty acids 82 biosynthesis 87 catechol‐O‐methyltransferase (COMT) 99 see also cytochrome P450 dihydroxyacetone phosphate CDPX2 syndrome 85 cystathionine β‐synthase, catalysis 88 biosynthesis 9, 12, 15, 36, 46 cells cysteine reduction 8, 11, 64 concepts of 2 biosynthesis 88 4,4‐dimethylcholesta-8(9),24‐dien-3β-ol 84 energy conservation 4 catabolism 92 4,8‐dimethylnonanoyl CoA 80 muscle 10, 28, 32, 35, 46, 94 γ‐glutamyl cycle 30 2,4‐dinitrophenol (DNP) 7 nerve 74 uses 88 2,3‐diphosphoglycerate (2,3‐DPG) see 2,3‐bisphosphoglycerate (2,3‐BPG) see also adipocytes; hepatocytes; red blood cells cysteinylglycine 30 disulfiram, in alcoholism treatment 48 β‐cells cytidine triphosphate (CTP) 110 DNA, purine biosynthesis 108 metabolism 121 cytochrome b (cyt b), in Q cycle 7 DNP (2,4‐dinitrophenol) 7

response 122 cytochrome b5, localization 68 docasanoic acid 78 4,7,10,13,16,19 cerebral oedema 116 cytochrome b5 reductase, localization 68 all cis-Δ -docosahexaenoic acid (DHA) 78 cerotic acid 78 cytochrome c (cyt c), electron transport 6 cis-7,10,13,16,19-docosapentaenoic acid 78 accumulation 79 cytochrome P450 cis-Δ13-docosenoic acid 78 cerotoyl CoA 78 adult Refsum’s disease 82 dodecanoic acid 78 cervonic acid see DHA (docosahexaenoic acid) catalysis 79, 82 dolichol, precursors 84 CGI-58 60 deficiency in cholesterol biosynthesis (Antley–Bixler disease) 85 DON (diazo‐oxo‐norleucin) 110 Chanarin–Dorfman syndrome 60 need for NADPH + H+ 30 l-DOPA decarboxylase 98 charge separation 6 role in ethanol metabolism 48 l-DOPA (levodopa) 98 chemiosmotic theory 6 X‐ALD 79 dopamine 98, 99 chenodeoxycholate biosynthesis 86 cytosol 2 and mental illness 98 CHILD syndrome 85 PEPCK overexpression in mouse muscle 43–4 2,3‐DPG see 2,3‐bisphosphoglycerate (2,3‐BPG) chlorpropamide, aldehyde dehydrogenase inhibition 48 drug metabolites, glucuronide conjugates 45 chlorpropamide alcohol flushing 48 dATP (deoxyadenosine triphosphate) 108 dTMP (deoxythymidine monophosphate), biosynthesis 110 cholane 84 DCCD (dicyclohexylcarbodiimide) 7 dTTP (deoxythymidine triphosphate), biosynthesis 110 cholate, biosynthesis 86 dCTP (deoxycytidine triphosphate) 110 dUMP (deoxyuridine monophosphate), biosynthesis 110 cholecystokinin, insulin secretion stimulation 121 debranching enzyme, deficiency 22 cholestane 84 decanoic acid 78 early fed state 94 5,7,9(11)‐cholestatrien‐3β‐ol 84 cis‐Δ4-decenoate, and MCAD deficiency 70, 71 eicosanoic acid 78 19‐nor‐5,7,9,(10)‐cholestatrien‐3β‐ol 84 cis‐Δ4-decenoyl CoA, oxidation 76 eicosanoid hormones, precursors 68 cholesterol 84–5 dehydratase and fatty acid elongation 68 eicosapentaenoic acid (EPA) 68–9, 78 biosynthesis 84, 85 7‐dehydrocholesterol, biosynthesis 84 in fish oils 68 and cancer 84 8‐dehydrocholesterol, biosynthesis 84 all cis-Δ5,8,11,14-eicosatetraenoic acid see arachidonic acid metabolism disorders 84 7‐dehydrocholesterol reductase 84 cis-Δ11-eicosenoic acid 78 cholesterol desmolase 86 14‐demethyllanosterol 84 electron‐transfer flavoprotein (ETF), in β-oxidation 70 ChREBP 56 dental decay electron transport chylomicrons 52, 59 absence in hereditary fructose intolerance 47 inhibition 7 citrate 20 xylitol chewing gum in prevention 44 processes 6 fatty acid synthesis 54 dental enamel, remineralization 44 endogenous depression 100 glycolysis inhibition 32 deoxyadenosine triphosphate (dATP), biosynthesis 108 endoplasmic reticulum 2 citrate , catalysis 50, 54, 56, 66 deoxycytidine triphosphate (dCTP), biosynthesis 110 and ethanol ingestion 48 citrate synthase deoxyguanosine triphosphate (dGTP), biosynthesis 108 fatty acid elongation 68 catalysis 72 deoxythymidine monophosphate (dTMP), biosynthesis 110 glucose 6‐phosphatase 36 metabolic channelling 104 deoxythymidine triphosphate (dTTP), biosynthesis 110 glucose 6‐phosphate translocator 22 citric acid cycle see Krebs citric acid cycle deoxyuridine (dUrd) as plasma marker for thymidylate synthase energy conservation in cells 4 citrullinaemia and Reye’s syndrome 117 inhibition 111 energy metabolism citrulline deoxyuridine monophosphate (dUMP), biosynthesis 110 via glucose metabolism 20–1 biosynthesis 102 dephosphorylation, protein 28 via triacylglycerol metabolism 18–19, 19 diffusion (metabolic channelling) 105 depression 100 energy storage, as fat 52, 56

126 Index

0002858194.indd 126 11/26/2016 10:23:31 AM enolase inhibition 14 phosphorylation 4 mechanisms 32 enoyl ACP reductase 106 P/O ratio 7 as nuclear anchor 47 enoyl CoA hydratase, catalysis 78 fluorouracil, inhibitory activity 110 gluconeogenesis 36, 37 Δ2-enoyl CoA hydratases, localization 70 folate, metabolism 108–9, 110, 111 acetyl CoA in 94 3,2‐enoyl CoA isomerase, catalysis 76, 77, 79 folate antagonists, mechanisms 110 via amino acid metabolism 94–5 trans-Δ2-enoyl CoA isomerase, catalysis 76 folinic acid, methotrexate toxicity ‘rescue’ 110 in diabetes 122 enoyl CoA reductase, catalysis 68 formate 108 from fatty acids, problems in mammals 40–1 entacapone 98 N-formiminoglutamate (FIGLU) 92 inborn errors and Reye‐like syndrome 116 N-formylkynurenine, biosynthesis 101 inhibition after ethanol consumption 48 in cells 2 FPP (farnesyl pyrophosphate) 85 in liver 94 co‐precipitation and substrate channelling 104 free fatty acids precursors 36, 40–1, 90, 94 EPA see eicosapentaenoic acid (EPA) biosynthesis 60 regulatory mechanisms 36–7 epimerase reaction 44 blood concentrations 116 in Reye’s syndrome 116, 117 epinephrine see adrenaline Reye’s syndrome 116 gluconeogenesis–glycolysis switch 94 epoxides, in hawkinsuria 99 see also fatty acids glucose erucic acid 78 fructokinase accumulation 118 erythropoietic porphyria, aetiology 115 catalysis 46 brain requirements 10, 20, 36, 40 essential fatty acids, therapeutic benefits 68–9 deficiency 47 homeostasis, requirements 36, 40, 47, 56, 90 essential fructosuria, aetiology 47 fructose insulin‐stimulated uptake 52 essential pentosuria, aetiology 44 intravenous, dangers of 46 metabolism see glycolysis esterification metabolism 46–7 nerve cell delivery 74 and fatty acid biosynthesis 54 fructose 1,6‐bisphosphatase (F 1,6‐bisPase) 36, 56, 122 phosphorylation 32 of fatty acids 58–9 deficiency 47 roles, in liver phosphorylase inhibition 28 estrane 84 inhibition 36 synthesis see gluconeogenesis ETF (electron‐transfer flavoprotein) 70 regulatory mechanisms 36 toxicity 122 ETF:ubiquinone (ETF:QO), roles, in carnitine shuttle 70 fructose 1,6‐bisphosphate 32 in type 2 diabetes 120 ethanol cleavage 12 glucose alanine cycle 90, 91 biochemical effects 48 pyruvate kinase activation 32, 56 glucose biosynthesis see gluconeogenesis drug interactions 48 fructose 1,6‐bisphosphate aldolase glucose‐dependent insulinotrophic polypeptide (GIP), insulin secretion fasting hypoglycaemia 48 deficiency 47 stimulation 120 metabolism 48–9 inhibition 47 glucose/fatty acid cycle 38 evening primrose oil, therapeutic benefits 68–9 fructose 2,6‐bisphosphate glucose 6‐phosphatase 22, 122 exemestane, aromatase inhibitor and breast cancer 87 biosynthesis 32 deficiency 22, 36 exercise fructose 1,6‐biphosphatase inhibition 36 localization 2, 36 biochemistry of 34–5 roles 56 glucose 1-phosphate cytosolic PEPCK overexpression 43–4 fructose 2,6‐bisphosphatase, bifunctional enzyme 32 biosynthesis 22, 24 effects on muscle protein 90 in diabetes 123 reactions, with uridine triphosphate 22 hitting the wall 34, 43 fructose intolerance, hereditary 47, 117 glucose 6‐phosphate 26 exocytosis, regulatory mechanisms 120 fructose 1-phosphate, biosynthesis 46, 47 accumulation 25 fructose 1-phosphate aldolase biosynthesis 12, 22, 24, 30 FABP (fatty acid‐binding protein) 60 catalysis 46, 47 glycolysis 24, 32 FAD (flavine adenine dinucleotide) 4 deficiency 47 glucose 6‐phosphate dehydrogenase 30, 56, 66

FADH 2 (flavine adenine dinucleotide (reduced)) 10 fructose 6‐phosphate deficiency 30 Fanconi–Bickel syndrome 120 availability 32 glucose transport aetiology 56, 57 biosynthesis 31, 46, 56 insulin in 122 farnesyl isoprenoid groups, precursors 84 fate of 30 in TAG synthesis 52–3, 54 farnesyl pyrophosphate (FPP) 85 glucokinase regulation 47 glucose transporters (GLUTs) 32, 34, 46 fasting see starvation ‘paradox’ 47 GLUT1 10 fat fructose transporter (GLUT5) 10, 46, 47 in red blood cells 32 biosynthesis see lipogenesis fructosuria, essential 47 in skeletal muscle 10, 35 as energy store 52, 56 fumarate, biosynthesis (purine nucleotide cycle) 38, 102 GLUT2 10, 23, 36, 37, 47 microvesicular accumulation in Reye’s syndrome 116 fumarylacetoacetase abnormal 56, 57, 120, 123 metabolism see lipolysis deficiency 96, 98 in liver 32, 56 sugar biosynthesis 40 recessive disorders 96, 98 GLUT3 10 fat cells see adipocytes fumarylacetoacetate, accumulation 96, 98 in nerve 74 fatty acid‐binding protein (FABP) 60 GLUT4 fatty acids 38 galactitol, metabolism 44 activation 52 activation in β-oxidation 18 galactokinase, deficiency 44 in adipose tissue 32 in adenosine triphosphate biosynthesis 18–19 galactosaemia, aetiology 44 in cardiomyocytes 32 biosynthesis 40, 41, 50, 52, 53, 59, 66, 106, 107 galactose 44 in skeletal muscle 10, 24, 25, 32, 35 precursors 50, 54–5, 58–9, 66 inborn errors of metabolism 44 translocation 32, 52 desaturation 68–9 galactose 1-phosphate uridyltransferase (Gal-1-PUT), deficiency 44 GLUT5 (fructose transporter) 10, 46, 47 essential 68–9 galanin, insulin secretion inhibition 121 roles 10, 46, 47 esterification, to triacylglycerols 54, 58–9, 66 Gal-1-PUT (galactose 1-phosphate uridyltransferase), deficiency 44 in skeletal muscle 10, 46

fuel reserve as triacylglycerol 34 GAR (glycinamide ribonucleotide), catalysis 108 α1→6‐glucosidase (AGL), catalysis 22 and glucose biosynthesis, problems in mammals 40–1 GDP (guanosine diphosphate) 4 glucuronate 44 metabolism, in diabetes mellitus 118 gene expression, insulin‐regulated 120 metabolism 45 mobilization 60–1, 62–3, 72 gene therapy, OTC deficiency 103 as vitamin C precursor 44 nomenclature 76, 77, 78 George III, porphyria 114 glucuronate/xylulose pathway, mechanisms 44 β-oxidation 70–1, 80 geranyl isoprenoid group, precursors 84 glucuronide conjugates 45 in diabetes 118 geranyl pyrophosphate (GPP) 85 glutamate re‐esterification 63 Gilbert’s syndrome, aetiology 115 accumulation, in Reye’s syndrome 117 fatty acid synthase complex, metabolic channelling 106–7 GIP (glucose‐dependent insulinotrophic polypeptide) 120 biosynthesis 66, 88, 90, 92, 102 fatty acyl CoA desaturases, activity 68 GKRP (glucokinase regulatory protein) 32, 47 catabolism 92 fatty aldehyde dehydrogenase 80 GLA (γ-linoleic acid) 68–9 fatty acid synthesis 66 fatty dicarboxylic acids 80 GLP-1 (glucagon‐like peptide-1) 120 γ-glutamyl cycle 30 favism 30 glucagon roles 88 F 1,6‐bisPase see fructose 1,6‐bisphosphatase in glycogenolysis 22, 23, 24, 26, 27 glutamate dehydrogenase, in urea biosynthesis 102 F 2,6‐bisPase see fructose 2,6‐bisphosphatase in glycolysis 32, 33, 37, 47 glutamine FCCP (carbonylcyanide‐p‐trifluoromethoxyphenylhydrazone), proton hormone‐sensitive lipase activation 36 acid/base regulation in kidney 88 transport leakage 7 lipolysis stimulation 60 biosynthesis 88, 112 ferrochelatase, activity 114, 115 glucagon‐like peptide-1 (GLP-1), insulin secretion stimulation 120 of GMP 108 fetal haemoglobin, affinity for 2,3‐bisphosphoglycerate 16 glucagonocentric diabetes 118, 122 in muscle 90 fetus, rejection 100 glucocorticoid steroids, biosynthesis 86 of purines 108

FO/F1 particles, roles 6, 7 glucogenic amino acids 94–5 formation in diabetes 118 fight or flight response 20, 22, 26 glucokinase as fuel for intestines 90 FIGLU (N-formiminoglutamate) 92 catalysis 2, 3, 32 roles 88 fish oils, therapeutic benefits 68–9 localization 32 glutamine antagonists, mechanisms 110 flavine adenine dinucleotide (FAD) 70 metabolic roles 12, 13, 15, 23, 31, 32, 56 glutamine synthetase, scavenger for ammonium ions 112 as hydrogen carrier 4, 5, 10 translocation 47 γ-glutamyl amino acid 30 reduction 4, 37 in diabetes 121, 122 γ-glutamyl cycle 30

flavine adenine dinucleotide (reduced) (FADH2) 10 regulation 32, 47 γ-glutamylcyclotransferase 30 biosynthesis 4, 8 glucokinase regulatory protein (GKRP) γ-glutamylcysteinylglycine see glutathione

Index 127

0002858194.indd 127 11/26/2016 10:23:31 AM γ-glutamyl transpeptidase (γ-GT) 30 inhibition 20, 22, 44 biosynthesis 72, 118 glutarate, excretion 70 in liver 22 oxidation 74 glutaric acidurias 70 mechanisms 10–13 d-3‐hydroxybutyrate dehydrogenase, catalysis 74 glutaryl CoA dehydrogenase, deficiency 70 and pentose phosphate pathway 30, 31, 54–7 4‐hydroxycyclohexylacetic acid (HCAA) 98 glutathione and Rapoport–Luebering shunt 16, 17 5‐hydroxyindoleacetic acid (5‐HIAA) 100 biosynthesis 30, 31 regulatory mechanisms 32–3 7‐α-hydroxylase (cholesterol 7‐α-hydroxylase), regulatory mechanisms 86 depletion (Hawkinsinurea) 98 in skeletal muscle 34, 35 6‐hydroxymelatonin 100 oxidized 31 unregulated after i.v. fructose 46 6‐hydroxymelatonin glucuronide, biosynthesis 100 reduced 30 glycolytic enzymes, deficiency in red blood cells 16, 17 hydroxymethylbilane, biosynthesis 114 roles 30 glycosyl transferase, catalysis 22 β-hydroxy-β-methylglutaric aciduria (3‐hydroxy 3‐methylglutaric aciduria) structure 30 glyoxylate, biosynthesis 41 96 glutathione peroxidase 31 glyoxylate cycle 41, 112 3‐hydroxy-3‐methylglutaric aciduria (HMG CoA lyase deficiency and glutathione reductase 30 glyoxysomes, roles, in germination 41 leucine catabolism) 96 GLUTs see glucose transporters GMP (guanosine monophosphate) 108 3‐hydroxy-3‐methylglutaryl CoA (HMG CoA), and leucine catabolism 91 glyceraldehyde gonane 84 3‐hydroxy-3‐methylglutaryl CoA (HMG CoA) lyase, and ketogenesis 72, 73 biosynthesis 46 gondoic acid 78 deficiency 96 insulin secretion stimulation 120 gout 3‐hydroxy-3‐methylglutaryl CoA (HMG CoA) reductase, and cholesterol glyceraldehyde 3‐phosphate aetiology 22, 108, 109 biosynthesis 84, 85 biosynthesis 12, 46, 56, 58, 59, 66 and hyperlactataemia 48 3‐hydroxy-3‐methylglutaryl CoA (HMG CoA) synthase oxidation 12 low‐fructose diet 30 cholesterol biosynthesis 84–5 glyceraldehyde 3‐phosphate dehydrogenase, catalysis 8 GPP (geranyl pyrophosphate) 85 ketogenesis 72–3 glycerol GSH see glutathione 4‐hydroxy-3‐methyoxymandelate (HMMA) 98 biosynthesis 49–51 GSK-3 (glycogen synthase kinase-3) 28 4‐hydroxyphenylpyruvate dioxygenase 95 metabolism, in diabetes mellitus 118 GSSG (oxidized glutathione) 31 4‐hydroxyphenylpyruvate oxidase 98 roles, as gluconeogenic precursor 36, 37, 40 γ-GT (γ-glutamyl transpeptidase) 30 deficiency 98 glycerol kinase GTP (guanosine triphosphate) 4, 13, 42, 43, 67 16‐hydroxyphytanic acid 82 catalysis 36, 40, 58, 63, 64, 66, 67 guanosine diphosphate (GDP) 4 2‐hydroxyphytanoyl CoA 80, 81 expression in white adipose tissue, debate 62 guanosine monophosphate (GMP) 108 2‐hydroxyphytanoyl CoA lyase 80, 81 glycerol 3‐phosphate guanosine triphosphate (GTP) 4, 13, 42, 43, 67 5‐hydroxytryptamine see serotonin biosynthesis see glyceroneogenesis l-gulonate, metabolism to vitamin C 44, 45 hyperammonaemia, in Reye’s syndrome 116 fatty acid re‐esterification 59, 63 Günther’s disease, aetiology 115 hyperbilirubinaemia 114 sources of 58, 59, 62, 63, 64, 65 hypercholesterolaemia, treatment 84 glycerol 3‐phosphate dehydrogenase 8, 12, 14 haem hyperglycaemia glycerol phosphate shuttle, mechanisms 8, 13 biosynthesis 114 aetiology 10, 56, 118 glyceroneogenesis 43, 59, 62, 63, 64–5, 66 catabolism 114 and glyceroneogenesis 64 glyceryl trierucate, Lorenzo’s oil 79 haemoglobin, fetal 16 post‐prandial 120 glyceryl trioleate, Lorenzo’s oil 79 haem oxygenase, catalysis 114 see also persistent hyperinsulinaemic hypoglycaemic of infancy (PHHI) glycinamide ribonucleotide (GAR), catalysis 108 Hartnup disease 100 hyperglycinaemia, non‐ketotic, aetiology 96 glycine 30, 108 hawkinsin, biosynthesis 98, 99 hyperinsulinaemia, aetiology 122 accumulation, and non‐ketotic hyperglycinaemia 96 hawkinsinuria hyperlactataemia biosynthesis 88 aetiology 98 aetiology 14 catabolism 92 and 5‐oxoprolinuria 30 and ethanol 48 roles 88, 109, 111, 112, 115 HCAA (4‐hydroxycyclohexylacetic acid) 98 and thiamine deficiency 14 glycine cleavage enzyme, deficiency 96 hepatocyte nuclear factor 1α (HNF1A) mutations 120 hyperlipidaemia in diabetes, aetiology 122 glycine cleavage system 92 hepatocyte nuclear factor 4α (HNF4A) mutations 120 hypermethioninaemia 98 glycine synthase, catalysis 88, 89 hepatocytes 102 hypertension glycogen glucokinase 32, 56 11-hydroxylase deficiency 87 biosynthesis see glycogenesis glucose transport 56 17‐hydroxylase deficiency 87 exhaustion 34 metabolic channelling studies 104 phaeochromocytoma 98 as fuel reserve 20, 34 hepatorenal tyrosinaemia (tyrosinaemia, type I) 96, 98 hypoglycaemia 120 hepatorenal accumulation 56 hereditary fructose intolerance, aetiology 47, 117 aetiology 10, 20, 22, 47, 71 structure 20 hereditary orotic aciduria 103, 111 and ethanol 48 glycogenesis 20–1, 22 Hers’ disease, aetiology 22 fasting 48, 56, 120 and ‘fight or flight’ response 20 hexacosanoic acid see cerotic acid prevention by proteolysis and gluconeogenesis 117 in liver 22, 23 hexadecanoic acid see palmitic acid and Reye’s syndrome 96, 116 mechanisms 25 cis-Δ9-hexadecenoic acid 78 hypoglycin A, metabolism 71 regulatory mechanisms 25, 28–9 hexanedioic acid, biosynthesis in MCAD deficiency 71 hypoketonaemia and Reye’s syndrome 117, 117 in skeletal muscle 22, 23, 24, 25, 46 hexanoic acid 78 hypophosphataemia, and diabetic ketoacidosis 16 and type 2 diabetes 122 hexanoyl carnitine, biosynthesis 71 hypoxanthine 112 see also insulin‐stimulated glycogen synthesis hexanoylglycine, biosynthesis 70 hypoxanthine–guanine phosphoribosyl transferase, deficiency 110 glycogenin 20 hexokinase hypoxanthine phosphoribosyl transferase 112 glycogen metabolism 22–7 catalysis 32, 33 anaerobic 14 deficiency 16, 17 IAPP (islet amyloid polypeptide) 121 in diabetes mellitus 122 hexose monophosphate shunt see pentose phosphate pathway ICDH (isocitrate dehydrogenase) 36, 38, 54 in liver 22, 23 5‐HIAA (5‐hydroxyindoleacetic acid) 100 IDO (indoleamine 2,3‐dioxygenase) 100 in muscle 24–5 histidase, deficiency 96 immune haemolysis, jaundice 114 metabolic demands 22 histidinaemia, aetiology 96 IMP (inosine monophosphate) and uric acid cycle 112 regulatory mechanisms 26–7 histidine, catabolism 92 inborn errors of metabolism see also glycogenesis; glycogenolysis HMG CoA see 3‐hydroxy-3‐methylglutaryl CoA (HMG CoA) entries amino acid disorders 96–9 glycogenolysis 14, 20 HMMA (4‐hydroxy-3‐methyoxymandelate) 98 cholesterol biosynthesis disorders 84, 85 in liver 22, 23 HNF see hepatocyte nuclear factor entries essential pentosuria 44 mechanisms 22, 23, 24, 25 homocysteine, and cardiovascular disease 108 fatty acid oxidation disorders 70, 71, 78–83 in skeletal muscle 24 homocysteine methyltransferase, methionine salvage pathway 89, 92, 93, fructokinase deficiency 47 glycogen phosphorylase 95, 97, 101, 108, 109, 111 fructose 1,6‐bisphosphatase deficiency 47 inhibition 47 homogentisate 1,2‐dioxygenase deficiency (alkaptonuria) 96 fructose 1-phosphate aldolase deficiency 47 properties and regulation 26, 27 homovanillic acid (HVA) 98, 99 galactose 44 glycogen storage 22 hormone‐sensitive lipase (HSL) glycogen storage disorders 16, 17 glycogen storage diseases catalysis 18, 60, 61, 72 glycolytic enzymes (red blood cells) 16, 17 liver 22, 23 regulatory mechanisms 60, 61 phenylketonuria 96, 98, 99 muscle 25 roles, in ketone body biosynthesis 36, 72 porphyrias 114–15 see also Fanconi–Bickel syndrome HSL see hormone‐sensitive lipase (HSL) purine and pyrimidine disorders 108–11 glycogen synthase HVA (homovanillic acid) 98, 99 Reye’s syndrome and Reye‐like syndrome 116, 117 activation 28 hydrogen carriers 4 tyrosinaemias 96, 98, 99 catalysis 22, 23 hydrophilicity (bilirubin conjugates) 114 urea cycle disorders 51, 52 inactivation 25, 26, 28 hydrophobicity (bilirubin) 114 indoleamine‐amine hypothesis for affective (bipolar) disease 100 properties 28 β-hydroxyacyl ACP dehydratase (fatty acid synthase complex) 106 indoleamine 2,3‐dioxygenase (IDO) 100 regulatory mechanisms 28 l-3‐hydroxyacyl CoA dehydrogenase indoleamine pathway 100 glycogen synthase kinase-3 (GSK-3) 123 bifunctional enzyme 78 inner membrane, composition 2 functions 28 catalysis 19, 41, 70, 78 inosine monophosphate (IMP) glycogen synthase phosphorylation 28 role, in β-oxidation 70, 71 Krebs uric acid cycle 112, 113 glycolysis 2, 3, 5 3‐hydroxyacyl CoA epimerase, issues 76–7 as purine precursor 108 anaerobic 14–15, 22, 34 3‐hydroxyanthranilate, biosynthesis 92 purine salvage pathway 109 enzymes in 10, 11, 32–3 d-3‐hydroxybutyrate stimulation of glycogen phosphorylase 34

128 Index

0002858194.indd 128 11/26/2016 10:23:31 AM insects, glucose metabolism 8, 13 lactate dehydrogenase, catalysis 14 mitochondrial role in gluconeogenesis 36, 37, 104 insulin 10–11 lactate (lactic acid) in oxaloacetate reduction 8, 9 gene transcription inhibition 56 accumulation in liver 22 plants (glyoxysomes) 41 gene transcription stimulation 56 alcohol (ethanol) induced production 48 metabolic channelling 104 glucose uptake stimulation 32, 122 biosynthesis 14, 94 malate synthase, in glyoxylate cycle 41 IRS-1 inhibition 123 Cori cycle 14 malic enzyme, malate decarboxylation 50 lipolysis inhibition 52 excess see lactic acidosis malonate 7 PEPCK inhibition 36, 67 in fatty acid biosynthesis 50 malonyl‐acetyl CoA-ACP transacylase (fatty acid synthase complex) 106 roles 120, 121 glycogen storage disease I 22–3 malonyl ACP, biosynthesis 54 signal transduction 29 roles 22, 36, 122 malonyl CoA insulin‐dependent diabetes (IDDM) 120 lactic acidosis 14 biosynthesis 50, 51, 53–5 insulin‐dependent glucose transporter see GLUT4 lactonase, catalysis 30 fatty acid transport inhibition 70 insulinoma 10 lanosterol and insulin secretion 120, 121 insulin receptors biosynthesis 84 mammals in adipocytes 52 demethylation 84 amino acid synthesis 88 defective 120 lanosterol 14‐α-demethylase 84 fatty acid desaturation 68 functions 10, 29, 52 lathosterol, biosynthesis 84 glucose biosynthesis from fatty acids, problems 40–1 in muscle cells 10 lauric acid 78 mania (bipolar disease), amine hypothesis 100 insulin resistance 38 LCAD (long‐chain acyl CoA dehydrogenase) 70, 71 mannose, insulin secretion stimulation 120 in liver 123 LCHAD (long‐chain hydroxyacyl CoA dehydrogenase) 70 MAO (monoamine oxidase) 89, 99, 100, 101 in type 2 diabetes 120, 122 deficiency 70 maple syrup urine disease 96 insulin secretion, metabolism 120 leptin 121, 123 MARCKS (myristoylated alanine‐rich C kinase substrates) 121 insulin‐stimulated glycogen synthesis 28, 29 Lesch–Nyhan syndrome 110 maturity‐onset diabetes see type 2 diabetes mechanisms 28, 29 leucine 96 maturity‐onset diabetes of young (MODY), aetiology 120 intermembrane space 2, 3, 4, 6, 7, 8, 13 catabolism 42, 96, 102 MCAD (medium‐chain acyl CoA dehydrogenase) 70 IPP (isopentenyl pyrophosphate) 85 insulin secretion stimulation 120 deficiency 70, 71 iron‐sulphur complexes (ETF:QO and fatty acid oxidation) 70 glyceroneogenesis 65 MCPA (methylenecyclopropylalanine) 71 IRS-1 (insulin receptor substrate-1) 123 ketogenesis 72, 73, 90, 91 medium‐chain acyl CoA dehydrogenase see MCAD (medium‐chain acyl islet amyloid polypeptide (IAPP), polymerization 121 metabolic disorders 96 CoA dehydrogenase) isobutyrate (maple syrup urine disease) 35, 96 oxidation 90 melatonin isocitrate dehydrogenase (ICDH), inhibition 36, 38, 52, 54 leucovorin, methotrexate toxicity rescue 110 biosynthesis 100 isocitrate lyase, in glyoxylate cycle 41 levodopa (l-DOPA) 98 catabolism 100 isoleucine ligandin, bilirubin transport 114 metabolism 100, 100 exercise metabolism 34 lignoceric acid 78 mental illness, and dopamine 98 metabolism disorders 96 linoleic acid 78 MEOS (microsomal ethanol‐oxidizing system) 48 oxidation 90, 91 as eicosanoid hormone precursor 68 mercaptopurine, inhibitory activity 108, 110 transamination 102 β-oxidation 70, 76, 77 metabolic acidosis 96, 98 isopentenyladenosine, biosynthesis 85 α-linolenic acid 78 metabolic channelling (substrate channelling) isopentenyl pyrophosphate (IPP), biosynthesis 85 γ-linolenic acid (GLA) 68–9, 78 enzyme organization 104–5 isotope dilution studies and metabolic channelling 104 lipase, hormone‐sensitive 18, 60–5 evidence for 104 isovalerate 96 lipogenesis 52–7, 66–7 fatty acid synthase complex 106–7 isovaleryl CoA dehydrogenase 91, 96 NADPH + H+ 30 isotope dilution studies 104 deficiency 117 fatty acid synthase complex 106, 107 urea cycle 104–5 lipolysis 18, 19, 43 metabolic charts, overview 2–3 Jamaican vomiting sickness (JVS) 71 in adipose tissue 60–3 metabolic fuel hypothesis, for insulin secretion 120 jaundice, neonatal 114 signalling defects in diabetes 118, 122 metabolic pathways juvenile‐onset diabetes 120 regulation of 60, 61 mutual dependence in Reye’s syndrome 116, 117 JVS (Jamaican vomiting sickness) 71 sport and exercise metabolism 34, 35 subcellular distribution 2–3 fatty acid esterification and re‐esterification 58, 59 metabolites, channelling see metabolic channelling (substrate Kandutsch and Russell pathway (cholesterol biosynthesis) 84 liver channelling) KCNJ11, β-cell KATP channel gene mutation 120 Cori cycle 14, 15 metadrenaline 98 kernicterus, aetiology 114 fatty acid esterification 58–9 metalloporphyrins 114 α-ketoacid dehydrogenase, branched‐chain (BCKADH), deficiency 90 fatty acid transport inhibition 70 metepinephrine 98 ketoacidosis, diabetic 118 fructose metabolism 46 N5,N10-methenyl tetrahydrofolate, biosynthesis 111 β-ketoacyl ACP reductase (fatty acid synthase complex) 106 functions 56 methionine, biosynthesis 108 β-ketoacyl ACP synthase (fatty acid synthase complex) 106 gluconeogenesis 36, 37 catabolism 92 3‐ketoacyl CoA transferase, catalysis 74 gluconeogenesis and Cori cycle 14 metabolism to fat 67 α-ketoadipate 92 glutathione in 30 methionine salvage pathway 108 ketogenesis glycogenesis in 20, 22, 28, 29 methotrexate and rheumatoid arthritis 109, 110 mechanisms 72 glycogen metabolism 22, 26 inhibitory activity 109 in Reye’s syndrome 117 glycogen storage 20, 22 α-methylacyl CoA racemase (AMACR) 80–3 ketogenic amino acids 72, 90 glycogen storage diseases 22, 23 deficiency 80, 81 α-ketoglutarate biosynthesis 48, 92, 102 glycolysis in 32, 56–7 and disease 82 α-ketoisocaproate, insulin secretion stimulation 120 insulin resistance see insulin resistance known as P504S in oncology (immunohistochemistry) 80 ketone bodies ketone bodies in 70, 72, 74 overexpression in tumours 80 biosynthesis 72–3, 118 Krebs cycle inhibition after ethanol consumption 48 3‐methyladipic acid 82 oxidation 74 metabolic pathways 2–3 4‐methyladipoyl CoA 82, 84 utilization 74–5 pentose phosphate pathway 31–7, 56–7 α-methylbutyrate, and maple syrup urine disease 96 ketosis, regulatory mechanisms 72 PFK-2/F 2,6‐bisPase bifunctional enzyme, isoenzymes 32 N-methyl-d-aspartate (NMDA) receptor, activation by glycine 96 ketothiolases phosphorylase inhibition 28 3‐O-methyldopa (3‐OMD) 98 deficiency 117 liver cells see hepatocytes methylenecyclopropylalanine (MCPA), (hypoglycin) metabolism 71 localization 70 London Underground map 2 N5,N10-methylene tetrahydrofolate 108, 109 Kir6.2 (potassium inwardly rectifying channel 6.2) 120 long‐chain acyl CoA dehydrogenase (LCAD), localization 71 glycine biosynthesis 88

knockout mice (HSL knockout in mouse) 60 long‐chain acyl CoA synthetase, catalysis 18, 71 methyl‐folate trap, and vitamin B12 108 Krebs citric acid cycle long‐chain hydroxyacyl CoA dehydrogenase (LCHAD), specificity 70 methylmalonic aciduria 96 acetyl CoA oxidation 38, 39 deficiency 70, 117 methylmalonyl CoA mutase, deficiency 96, 117 in ATP biosynthesis 13 Lorenzo’s oil, studies 78–9 N5-methyl tetrahydrofolate, biosynthesis 109 catalytic mechanisms 4 lovastatin 85 α-methyl-p-tyrosine (and phaeochromocytoma) 98 in fatty acid oxidation 19 Lowenstein’s cycle see purine nucleotide cycle mevalonate 85 in glucose metabolism 10, 11–13 lyase (arginosuccinate lyase) 105 mevastatin 85 glyoxylate shunt 40, 41 lysine, metabolism to fat 66, 67 microsomal ethanol‐oxidizing system (MEOS), roles, in ethanol inhibition following ethanol consumption 48 catabolism 92 metabolism 48 ketone body utilization 74 lysophosphatidate, biosynthesis 58, 59, 63 milk, galactose 44 in mitochondrion 2, 3 mind’s clock see biological clock regulatory mechanisms 38–9 McArdle’s disease, aetiology 25 mineralocorticoid, biosynthesis 86, 87 Krebs–Henseleit ornithine cycle 102–3 MADD see glutaric acidurias Mitchell’s chemiosmotic theory 6 Krebs–Kornberg glyoxylate cycle 41 malate mitochondrion 2 Krebs uric acid cycle 112–13 biosynthesis 48, 50 ATP biosynthesis 4, 13 kynureninase decarboxylation (malic enzyme) 50, 51 metabolic pathways in 60, 68, 78, 82, 92 biosynthesis 100, 101 malate/aspartate shuttle 9, 12, 13 oxygen transport 14, 16, 17 catalysis 92, 93 malate dehydrogenase PEPCK in mitochondria 66, 67 kynurenine, biosynthesis 100, 101 catalysis 4, 8, 9 respiratory chain 2, 3, 6–7 kynurenine pathway 100 decarboxylating (malic enzyme) 50, 51 swollen in Reye’s disease 116

Index 129

0002858194.indd 129 11/26/2016 10:23:31 AM mobilizing lipase see hormone‐sensitive lipase (HSL) NTBC see 2‐(2‐nitro-4‐trifluoro‐methylbenzoyl)-1,3‐cyclohexanedione and NADPH biosynthesis 30–1, 50–7, 66 MODY (maturity‐onset diabetes of young) 120 (NTBC) in red blood cells 31 , catalysis 60 nucleoside diphosphate kinase, catalysis 4, 12 regulatory mechanisms 30 monoamine oxidase (MAO) 99, 100, 101 5′-, and adenosine production 34 pentosuria, essential 44 monodehydroascorbate reductase 79 PEPCK see phosphoenolpyruvate carboxykinase (PEPCK) monohydroascorbate reductase 41 obesity 65 PEPCK-C gene 66 montanic acid 78 and perilipin 60 perilipin 60 multiple acyl CoA dehydrogenase deficiency (MADD) 70 all cis-Δ9,12-octadecadienoate see linoleic acid peripheral benzodiazepine receptor (PBR), and cholesterol uptake 86 multiple carboxylase deficiency 117 all cis-Δ6,9,12-octadecadienoic acid 78 permanent neonatal diabetes mellitus (PNDM) 121 muscle all cis-Δ9,12,15-octadecadienoic acid 78 peroxisomal ATP-binding cassette transporter (ABCD1) and X-ALD 78–9 cardiac 32, 33 cis-Δ9-octadecenoic acid 78 peroxisomal β-ketothiolase 78 Cori cycle 14 cis-Δ11-octadecenoic acid 78 peroxisomal β-oxidation 78–9, 81, 83 and diabetes mellitus 120, 122 octanedioic acid, biosynthesis in MCAD deficiency 71 peroxisome proliferator activated receptor (PPAR-γ), glitazones and fructose metabolism 46 octanoic acid 78 diabetes 64 glucose/alanine cycle 90 octanoyl carnitine, biosynthesis in MCAD deficiency 71 peroxisomes 80 glucose metabolism 10, 20, 22 octodecanoic acid 78 oxidation of ethanol 48 glycogen metabolism 22, 24–5, 26 oculocutaneous tyrosinaemia (tyrosinaemia, type II) 98 proliferation 64, 78 glycogen storage 22 oestradiol, biosynthesis 86, 87 persistent hyperinsulinaemic hypoglycaemic of infancy (PHHI), glycogen storage diseases 25 oleic acid 78 aetiology 120 glycolysis, regulatory mechanisms 32–5 oligomycin, proton transport inhibition 7 PFK see phosphofructokinase (PFK) insulin resistance 122 3‐OMD (3‐O-methyldopa) 98 PFK-1 see phosphofructokinase (PFK-1) red 14 OMP (orotidine monophosphate) 110 PFK-2 see phosphofructokinase (PFK-2) white 14 ‘one‐carbon pool’ 108 phaeochromocytoma, aetiology 98 see also skeletal muscle ornithine 67, 102 phenylalanine, inborn errors of metabolism 98, 99 muscle AMP deaminase, deficiency 38 catabolism 88, 92 phenylalanine monooxygenase deficiency 96, 99 muscle cells, glucose transport 10, 94, 118 transamination 92 phenylketonuria (PKU) 96, 97, 98, 99 muscle protein, metabolism and gluconeogenesis 36 ornithine cycle see urea cycle aetiology 98 myoadenylate deaminase, deficiency 38 ornithine transcarbamoylase (OTC), deficiency 102–3 toxic metabolite hypothesis 98 myoglobin, roles, in oxygen transport 16 gene therapy 103 transport hypothesis 98 myristic acid 78 orotate, biosynthesis 103 phenylpyruvate, biosynthesis 98 myristoylated alanine‐rich C kinase substrates (MARCKS) 121 orotate phosphoribosyl transferase, bifunctional enzyme 110, 111 PHHI (persistent hyperinsulinaemic hypoglycaemic of infancy) 120 myxothiazol 7 orotic aciduria 103, 111 phlorizin 121 orotidine monophosphate (OMP), biosynthesis 110, 111 phorbol esters 121 NAD+ see nicotinamide adenine dinucleotide (NAD+) orotidine monophosphate decarboxylase (bifunctional enzyme) 111 phosphatidate, as intermediate 59, 63, 120 NADH see nicotinamide adenine dinucleotide (NADH) OTC see ornithine transcarbamoylase (OTC) phosphatidylcholine, biosynthesis, role of S-adenosylmethionine NADH/NAD+ ratio and ethanol metabolism 48 outer mitochondrial membrane, composition 2 (SAM) 108 NADP+ see nicotinamide adenine dinucleotide phosphate (NADP+) ovaries, sex hormone biosynthesis 86 phosphatidylethanolamine, methylation, role of S-adenosylmethionine NADPH see nicotinamide adenine dinucleotide oxaloacetate (SAM) 108 phosphate (NADPH) in Krebs cycle 38, 41, 43 phosphatidylinositol 4,5‐bisphosphate, metabolism 123 NAG (N-acetylglutamate) 102 malate/aspartate shuttle 9 phosphatidylinositol 3,4,5‐trisphosphate, biosynthesis 123 neonates pyruvate/malate cycle 50 3′-phosphoadenosine-5′-phosphosulphate (PAPS) 100 diabetes 120 reduction in ethanol metabolism 48 phosphocreatine, ATP production 4, 34 glycine accumulation 96 transamination in urea cycle 102 phosphoenolpyruvate 14 insulin receptor defects 120 α-oxidation of fatty acids 80 phosphoenolpyruvate carboxykinase (PEPCK) and hepatic jaundice, treatment with Sn‐mesoporphyrin 114 phytanic acid 80, 81 gluconeogenesis 36 neuroblastoma, aetiology 98 β-oxidation of fatty acids 18, 19, 70–3, 76–7, 80 cytosolic, overexpression in muscle (supermouse) 42–3 neurochemical diseases 100 in ATP biosynthesis 2, 3 and glyceroneogenesis in adipose tissue 64 niacin, deficiency 100 linoleic acid 70, 76, 77 inhibition by insulin 36 nicotinamide 100 in mitochondrion 78, 82 mitochondrial PEPCK 66, 67 nicotinamide adenine dinucleotide (NAD+) peroxisomal 78–9, 80–3 regulatory mechanisms 64 availability 4, 5 in plants 41 phosphofructokinase (PFK), deficiency in red blood cells 16 availability and β-oxidation 70 pristanoyl CoA 80 phosphofructokinase-1 (PFK-1) 2, 56 biosynthesis 100 and Reye’s syndrome 116 deficiency in muscle 25 as hydrogen carrier 4 ω-oxidation of fatty acids 79, 80, 82–3 inhibition 36, 54 precursors 66 phytanic acid 82, 83 metabolic roles 32, 56 reduction 10, 11, 14 phytanoate 82 regulation by fructose 2,6‐bisphosphate 32, 33 nicotinamide adenine dinucleotide (NADH) oxidative phosphorylation 2, 4, 6, 8, 12, 18, 18 phosphofructokinase-2 (PFK-2), bifunctional enzyme 32, 56 biosynthesis 4, 10 not active in red blood cells 16, 17 phosphoglucomutase 22 oxidation 6, 7, 8–9, 13 oxidized glutathione (GSSG) 31 6‐phosphogluconate dehydrogenase 30 P/O ratio 12, 13 3‐oxoacyl CoA thiolases, localization 70 phosphoglucose isomerase 31 pyruvate dehydrogenase inhibition in diabetes 36 5‐oxoprolinuria 30 deficiency in red blood cells 16 nicotinamide adenine dinucleotide phosphate (NADP+), availability and oxygen debt 14 2‐phosphoglycerate, biosynthesis 14, 94 pentose phosphate pathway 30, 31 oxygen transport, in red blood cells 16 phosphoglycerate kinase, in glycolysis 4, 12, 28 nicotinamide adenine dinucleotide phosphate (NADPH) phosphoinositide‐dependent kinase (PDK) 123 biosynthesis 30–1, 50–7 palmitic acid (palmitate) phosphoinositide‐dependent kinase-1 (PDK-1), functions 123 NADPH biosynthesis, cytosolic isocitrate dehydrogenase 66, 67 biosynthesis 52–5, 58, 106, 107 phosphopantetheine and fatty acid synthase complex 106 and pentose phosphate pathway 50 oxidation 18, 19, 116 phosphoribosyl pyrophosphate (PRPP) and salvage pathway 110 and pyruvate/malate cycle 50 palmitoleic acid 78 biosynthesis 108 nicotinic acid 100 palmitoleoyl CoA, biosynthesis 68 in uric acid cycle 112 hormone‐sensitive lipase, inhibition at pharmacological dose 59 palmitoyl CoA phosphoribosyl transferases (PRTs), catalysis 110 NIDDM see type 2 diabetes biosynthesis (mitochondrial chain elongation) 16, 17 phosphorylase kinase nitric oxide, from arginine 88 desaturation 68 activation 25, 26 nitrogen, in urea biosynthesis 102, 103 glycogen synthase phosphorylation 26 nitrogen excretion α-cells and glucagon 36, 122 phosphorylases (glycogen) Krebs urea cycle 102 β-cells and insulin 10, 28, 32, 60, 61, 120, 121 activation 25 Krebs uric acid cycle 112 PAPS (3′-phosphoadenosine-5′-phosphosulphate) 101 binding and inactivation of glycogen synthesis 123 2‐(2‐nitro-4‐trifluoro‐methylbenzoyl)-1,3‐cyclohexanedione (NTBC) Parkinson’s disease, aetiology 98 catalysis 22, 23, 24 toxicity 98 Pasteur effect 14, 15 deficiency 22 in type 1 tyrosinaemia treatment 96, 97, 98, 99 PBG (porphobilinogen) 114 inactivation 26 NMDA (N-methyl-d-aspartate) receptor and glycine 96 PBR (peripheral benzodiazepine receptor) and cholesterol uptake 86 inhibition 28 nomenclature PCOS (polycystic ovary syndrome) 87 and hereditary fructose intolerance 47 fatty acids 76, 77, 78 PDE-3B (cyclic AMP phosphodiesterase-3B) 28, 29 properties 22 steroids 84 PDH see pyruvate dehydrogenase (PDH) regulatory mechanisms 26 non‐essential amino acids 88–9 PDK (phosphoinositide‐dependent kinase) 123 phosphorylation non‐insulin‐dependent diabetes mellitus (NIDDM) see type 2 diabetes PDK-1 (phosphoinositide‐dependent kinase-1) 123 glycerol 36, 62–4 non‐ketotic hyperglycinaemia 96 PDK/PKB hypothesis 123 oxidative phosphorylation 2, 4, 6, 8, 12, 16, 17, 18, 18 noradrenaline (norepinephrine) PDK/PKB pathway 123 protein‐serine phosphorylation and regulation of bifunctional S-adenosylmethionine (SAM) methylation 108 PDT (photodynamic therapy) 114 enzyme 32, 33 lipolysis stimulation 60 pellagra, aetiology 100 substrate‐level phosphorylation 4, 13, 18, 18 methylation 99, 108 pentose phosphate pathway 30 photodynamic therapy (PDT), cancer treatment 114 in phaeochromocytoma 98 enzymes in 2, 3 photosensitivity 114 14‐norlanosterol 84 in fatty acid biosynthesis 52–5 phytanic acid normetepinephrine (normetadrenaline) 98 lipogenesis 56–7 dietary 80

130 Index

0002858194.indd 130 11/26/2016 10:23:31 AM α-oxidation 80, 81, 82 protoporphyrinogen IX, biosynthesis 114 SERCA (sarco(endo)plasmic reticulum CA2+ ATPase) 121 ω-oxidation 82, 83 Prozac 100 serine phytanoate, ω-oxidation 82 PRPP see phosphoribosyl pyrophosphate (PRPP) and salvage pathway biosynthesis by ‘phosphorylated pathway’ 88 phytanoyl CoA 2‐hydroxylase 80 PRPP amidotransferase 112 catabolism 92 deficiency 80 PRTs (phosphoribosyl transferases) 110 as glycine precursor 108 phytol metabolism 80, 81 purine nucleotide cycle 38, 39, 103 phosphorylation (covalent modification of proteins) 26, 28, 32, 60, 61 picolinic acid (picolinate), biosynthesis 100, 101 anaplerosis and Krebs cycle 38, 39 uses 88 piericidin, electron transport inhibition 7 purinergic agonists, insulin secretion stimulation 121 serine hydroxymethyltransferase, catalysis 88, 108, 110 pineal gland 100 purines, biosynthesis 108–9, 110 serotonin pinealocytes 100 pyrimidine biosynthesis 110–11 biosynthesis 100 PK see pyruvate kinase (PK) pyroglutamic aciduria (5‐oxoprolinuria) 30 metabolism 100 PKA see protein kinase A (PKA) pyruvate serotonin reuptake inhibitors 100 PKB see protein kinase B (PKB) oxidation 10 sex hormones, biosynthesis 86, 87 PKC see protein kinase C (PKC) pyruvate/malate cycle 50, 51, 66, 67 short‐chain acyl CoA dehydrogenase (SCAD), localization 70 PKG see protein kinase G (PKG) reduction 14, 15 short‐chain fatty acids, elongation 68, 69 PKU see phenylketonuria (PKU) reduction to lactate following ethanol consumption 48 short‐chain hydroxyacyl CoA dehydrogenase (SCHAD), specificity 71 plants pyruvate carboxylase SIDS (sudden infant death syndrome) 70 Krebs–Kornberg glyoxylate cycle 41 activation 36, 37, 117 signal transduction, insulin 29 β-oxidation 41 catalysis 50, 66, 104 simvastatin 85 polycystic ovary syndrome (PCOS) 87 pyruvate/malate cycle 50, 51, 66, 67 singlet oxygen, photosensitive porphyria 114 polyol osmotic theory for formation of diabetic cataracts 44 regulatory mechanisms 36 skeletal muscle P/O ratios 7, 12, 13, 18, 19, 74, 112 stimulation 36, 122 Cori cycle 14 porin, in outer membrane 2 substrate channelling 104 cytosolic PEPCK, overexpression in muscle (supermouse) 42–3 porphobilinogen (PBG), biosynthesis 114 pyruvate carrier, substrate channelling 104 glycogenolysis 24–5 porphobilinogen (PBG) deaminase deficiency (acute intermittent pyruvate dehydrogenase (PDH) GLUTs (glucose transporters) 35 porphyria) 115 activation by insulin 66 PFK-2/F 2,6‐bisPase isoenzymes 32, 33 porphobilinogen (PBG) synthase, inhibition by succinylacetone in catalysis 66 skin cancer, treatment 114 tyrosinaemia I 96, 98 cofactors 10, 14 Smith–Lemli–Opitz syndrome 84 porphyria cutanea tarda, aetiology 115 glucose/fatty acid cycle 38, 39 Sn‐mesoporphyrin 114 porphyrias, aetiology 114, 115 inhibition 34, 35, 49, 94 sorbinil, as aldose reductase inhibitor 44, 45 porphyrin, metabolism 114–15 regulatory mechanisms 38, 39 sorbitol, metabolism 44, 45 potassium channels, adenosine triphosphate‐sensitive (KATP substrate channelling 104 sorbitol dehydrogenase, catalysis 44 channels) 120, 121 pyruvate kinase (PK) 56 sport, biochemistry of (see also ‘supermouse’) 34–5, 42, 43 potassium inwardly rectifying channel 6.2 (Kir6.2) 120 activation by -2A 56 squalene, biosynthesis 84 PP-1 see protein phosphatase-1 (PP-1) deficiency in red blood cells 16 squalestatin 85 PP-1G see protein phosphatase-1G (PP-1G) in glycolysis 4, 32 SREBP, regulation of fatty acid and cholesterol biosynthesis 56 PP-2A see protein phosphatase-2A (PP-2A) regulation in supermouse 42, 43 starflower oil, therapeutic benefits 68–9 PPAR-γ (peroxisome proliferator activated receptor), glitazones and pyruvate/malate cycle, and NADPH biosynthesis 50–1, 66 StAR (steroid acute regulatory) protein 86 diabetes 64 starvation PP inhibitor-1 26, 28 Q cycle, mechanisms 6, 7 amino acid metabolism 94–5 pravastatin 85 quinolinate , biosynthesis 100 brain energy requirement during 72, 74 pregnane 84 fatty acid mobilization 18, 38 pregnenolone, biosynthesis 86 Rabson–Mendenhall syndrome, aetiology, radioisotope dilution and and gluconeogenesis 36, 94–5 prenylated proteins 85 substrate channelling 104 glucose alanine cycle 90 preproinsulin, metabolism 121 Randle cycle see glucose/fatty acid cycle glycogen 20–7 primers, glycogen 22 Rapoport–Luebering shunt (2,3‐BPG) 16–17 metabolic pathways in liver 116–17, 117 pristanal 80 reactive depression 100 muscle protein metabolism during 90 pristanic acid 80 red blood cells statins (HMG CoA reductase inhibitors) 84, 85 pristanoyl CoA, β-oxidation 80 Cori cycle 14–15 stearic acid 78 progesterone enzyme deficiencies 16 sterocobilin, biosynthesis 114 biosynthesis 87 oxygen transport and 2,3‐BPG 16, 17 steroid acute regulatory (StAR) protein, regulatory mechanisms 86 nomenclature 85 pentose phosphate pathway and reduced glutathione 30, 31 steroid hormones 84, 86 proinsulin, metabolism 121, 122 reductases (fatty acid) 68 biosynthesis 87 proline re‐esterification of fatty acids 60 steroids, nomenclature 84 biosynthesis 88 Refsum’s disease 80, 82 sterol response element binding protein see SREBP catabolism 92 rescue pathways 80, 82 stigmatellin 7 proline oxygenase, catalysis 92 respiratory chain 6–7, 12 Streptococcus mutans, and xylitol 44 propionyl CoA, product of ω-oxidation 82 ATP biosynthesis 6–7 suberic acid and MCAD deficiency 70 propionyl CoA carboxylase, deficiency 96 in fasting 117 suberylglycine and MCAD deficiency 70 14‐3‐3 protein 101 in fatty acid oxidation 18, 19, 70, 71 substrate‐level phosphorylation 4, 13 protein kinase A (PKA) hydrogen transport 10 succinate, biosynthesis and glyoxylate cycle 41 activation 24, 26–7, 32–3, 120 inhibitors of 7 succinate dehydrogenase glycogen metabolism 24–7 and Reye’s syndrome 116 catalysis 4, 12 inhibition by insulin and A-kinase anchoring protein (AKAP) 26 Reye‐like syndrome 116 inhibition by malonate 7 melatonin biosynthesis 100 Reye’s syndrome roles, in respiratory chain 2, 3 roles 24–9, 32, 34, 37, 60, 61 aetiology 116, 117 succinic acid esters, and insulin secretion 121 protein kinase B (PKB) 123 diagnostic criteria 116 succinylacetone protein kinase C (PKC) 120 rheumatoid arthritis and methotrexate 110 accumulation, tyrosinaemia type I 98 activation and sorbitol metabolism 45, 120, 121 ribose 1,5‐bisphosphate and PFK-1 56 porphobilinogen synthase inhibition 98, 115 protein kinase G (PKG), and ANF in exercise‐stressed heart muscle 60, 61 ribose 5‐phosphate succinyl CoA protein metabolism glycogen storage disease I 22 biosynthesis 4, 35, 92, 93 to acetyl CoA 92 in purine biosynthesis 31, 108 catabolism of ketogenic amino acids 91 in diabetes mellitus 118 ribulose 5‐phosphate, biosynthesis 30 condensation 114 during fasting 90 Richner–Hanhart syndrome (tyrosinaemia type II) 98 and ketone body utilization 75 to fatty acids 66–7 Rieske protein 7 succinyl CoA synthetase 12, 13 gluconeogenesis 94–5 RNA, biosynthesis 108 catalysis 4, 19 protein phosphatase-1 (PP-1) 26–9 rosiglitazone and glycerol kinase in adipose tissue debate 62 sucrose, average daily intake 46 inactivation 26 rotenone, electron transport inhibition 7 sudden infant death syndrome (SIDS) 70 regulatory mechanisms in liver 28, 122 sugars, biosynthesis from fats 41 protein phosphatase-1G (PP-1G) 26 SAD (seasonal affective disorder) 100 6‐sulphatoxymelatonin, biosynthesis 100 protein phosphatase-2A (PP-2A) 28 salvage pathways sulphonylurea receptor, potassium channel closure 120 activation by xyulose 5‐phosphate 57 methionine 108 sulphonylureas 120 ChREBP dephosphorylation 56 purines/pyrimidines 110 suprachiasmatic nuclei (SCN) 100 PFK-2/F 2,6‐bisPase dephosphorylation 57 SAM see S-adenosylmethionine (SAM) synaptotagmin, as calcium sensor for insulin secretion 120 phosphorylase kinase dephosphorylation 26, 27, 28 sarco(endo)plasmic reticulum CA2+ ATPase (SERCA), catalysis 121 protein phosphatase inhibitor-1, activity 26 SCAD (short‐chain acyl CoA dehydrogenase) 70 TAGs see triacylglycerols (TAGs) proteosomal proteolysis of AANAT 100 SCHAD (short‐chain hydroxyacyl CoA dehydrogenase) 71 Tarui’s disease, aetiology 25 proton channels 6, 7 schizophrenia and serine hydroxymethyltransferase deficiency 88 TDO (tryptophan 2,3‐dioxygenase) 100 proton extrusion 7 dopamine hypothesis 98 testes, sex hormone biosynthesis 86 proton transport SCN (suprachiasmatic nuclei) 100 testosterone, biosynthesis 86, 87 inhibition 7 seasonal affective disorder (SAD) 100 tetracosanoic acid 78 processes 6 sebacic acid in MCAD deficiency 70, 71 tetradecanoic acid 78 protoporphyrin IX, biosynthesis 114 seeds, sugar biosynthesis from fat 41 trans-Δ2-tetraenoic acid 78

Index 131

0002858194.indd 131 11/26/2016 10:23:32 AM tetrahydrobiopterin, biosynthesis, impaired 96, 98 and insulin resistance 120 urobilinogen, biosynthesis 114 tetrahydrofolate (THF), biosynthesis 108 in adipose tissue 120 uroporphyrinogen I, biosynthesis 114 tetramethyl-p-phenyldiamine (TMPD), in respiratory chain studies 7 lifestyle influences 120 uroporphyrinogen III, biosynthesis 114 thenoyltrifluoroacetone, electron transport inhibition 7 in liver 122–3 ursodeoxycholic acid (UDCA) and obstetric cholestasis 86 thermogenesis 6, 7, 64 in muscle 120 UTP see uridine triphosphate (UTP) thermogenin 7 risk factors 120 THF (tetrahydrofolate) 108 type I glycogen storage disease, aetiology 22 vaccenic acid 78 thiamine deficiency, and hyperlactataemia 14 type III glycogen storage disease, aetiology 22 valine thiazolidinediones (TZDs, glitazones) and PEPCK 64 type V glycogen storage disease, aetiology 25 catabolism 34, 90, 96, 102 and fatty acid synthase complex 106 type VI glycogen storage disease, aetiology 22 metabolism disorders 96 threonine type VII glycogen storage disease, aetiology 25 oxidation 90 catabolism by dehydratase pathway in humans 92 type XI glycogen storage disease see Fanconi–Bickel syndrome vanillylmandelic acid (VMA) 98 see also chart, back cover tyrosinaemia 96, 98, 99 variegate porphyria, aetiology 115 catabolism by amino acetone pathway in animals see chart, back cover type I (hepatorenal) vascular damage, and sorbitol metabolism 44 threonine dehydratase pathway for threonine catabolism 92 aetiology 96, 98 very‐long‐chain acyl CoA dehydrogenase (VLCAD), in carnitine thymidylate synthase treatment 96, 98 shuttle 70 catalysis 110, 111 type II (oculocutaneous) 98 very‐long‐chain acyl CoA synthetase 79 inhibition 110, 111 type III 98 catalysis 78 thyroid hormones 88, 89 tyrosinase deficiency, albinism 96 very‐long‐chain fatty acids, chain shortening 78, 79, 80 timnodonic acid see eicosapentanoic acid (EPA) tyrosine very‐low‐density lipoproteins (VLDLs) tin mesoporphyrin 114 biosynthesis 88 secretion 122 TMPD (tetramethyl-p-phenyldiamine) 7 inborn errors of metabolism 96, 97, 98, 99 triacylglycerol transport 58, 59

tolcapone 98 metabolism to fat 66 vitamin B6, and homocysteine catabolism 109

toxic metabolite hypothesis (phenylketonuria, PKU) 98 uses 88 vitamin B12 108 α-toxin (metabolic channelling urea cycle) 104, 105 tyrosine aminotransferase, recessive disorder 98, 99 and homocysteine catabolism 109 transamination route, urea biosynthesis 102, 103 tyrosine 3‐monooxygenase, inhibition by α-methyl-p-tyrosine and methyl‐folate trap 108 transdeamination route, urea biosynthesis 102, 103 98, 99 and methylmalonic aciduria 96 transport hypothesis (phenylketonuria, PKU) 98 TZDs (thiazolidinediones, glitazones) and glyceroneogenesis 64, 65 vitamin C, biosynthesis 44 triacylglycerol/fatty acid cycle, mechanisms 62–5 vitamin D, precursors 85, 86 triacylglycerol lipase see hormone‐sensitive lipase (HSL) ubiquinol, in respiratory chain 6, 7 VLCAD (very‐long‐chain acyl CoA dehydrogenase), in carnitine triacylglycerols (TAGs) 18, 19, 40, 52–65 ubiquinone shuttle 70 biosynthesis (in supermouse) 43 precursors 84 VLDLs see very‐low‐density lipoproteins (VLDLs) in diabetes 118 in respiratory chain 6, 7, 8 VMA (vanillylmandelic acid) 98 ketogenesis 72 roles, in fatty acid oxidation 70 voltage‐dependent calcium channels 120 lipolysis 60, 61 UDCA see ursodeoxycholic acid (UDCA) and obstetric cholestasis von Gierke’s disease, aetiology 22 metabolism 40 UDP (uridine diphosphate) 110 tricarboxylate transporter 54 UDP-glucose 22 white adipose tissue metabolic channelling 104 UDP glucuronate see uridine diphosphate glucuronate fatty acid mobilization from 60–5 tricarboxylic acid cycle see Krebs citric acid cycle UDP glucuronyltransferase 44 glyceroneogenesis 64, 65 trifunctional enzyme, mitochondrial β-oxidation of fatty acids UMP (uridine monophosphate) 110 70, 71, 116 uncoupling protein, and thermogenesis 7 xanthine monophosphate (XMP), amination 108 see triacylglycerols (TAGs) unsaturated fatty acids, β-oxidation 76–7 xanthurenate 101 tri‐iodothyronine 98 urea, biosynthesis 102 X-linked adrenoleukodystrophy (X-ALD) 79 trimethoprim 109 urea cycle XMP (xanthine monophosphate), amination 108 triose kinase, catalysis 46 discovery by Krebs 112 xylitol 44 triose phosphates, biosynthesis 12 mechanisms 102–3 biosynthesis 44 tripalmitin, metabolism 50–67 metabolic channelling 104–5 dental decay prevention 44 triparanol 85 in Reye’s syndrome 116 metabolism 44, 45 tryptophan ureotelism 112 xylulose 44 catabolism 92 uric acid, and gout 110 xylulose 5‐phosphate and protein phosphatase-2A activation 56 in depression treatment 100 uric acid cycle 112 biosynthesis 44 and lipogenesis 66 uricotelism 112 l-xylulose reductase, deficiency 44 metabolism 100–1 uridine diphosphate glucose (UDP-glucose), biosynthesis 22 oxidation 92 uridine diphosphate glucuronate 44 yeast, alcoholic fermentation 15 tryptophan 2,3‐dioxygenase (TDO), catalysis 100 uridine diphosphate (UDP) 110 tryptophan hydroxylase 100, 101 uridine monophosphate (UMP), biosynthesis 110 Zellweger syndrome, aetiology 80 tryptophan pyrrolase see tryptophan 2,3‐dioxygenase (TDO) uridine triphosphate (UTP) zona fasciculata, cortisol biosynthesis 86 type 1 diabetes, aetiology 120 biosynthesis 110 zona glomerulosa, aldosterone biosynthesis 86 type 2 diabetes reactions, with glucose 1-phosphate 22 zona reticularis, cortisol biosynthesis 86 aetiology 120 urobilin, biosynthesis 114 zymosterol, biosynthesis 85

132 Index

0002858194.indd 132 11/26/2016 10:23:32 AM 0002858194.indd 133 11/26/2016 10:23:32 AM glycolysis

CH CH COO– 1,3-bisphosphoglycerate 2 +NH 3 ADP phosphoglycerate biosynthesis of kinase ATP nucleotides, creatine, α-ketoglutarate porphyrins, glutathione NAD+ NADH+H+ COO– glutamate phenylalanine HCOH 3-phospho 3-phospho tetrahydrobiopterin + dehydrogenase 3-phosphoserine O NADP hydroxypyruvate -ketoglutarate serine 2 Cytosol CH OPO 2– α COO– 4-monooxygenase dihydrobiopterin 2 3 aminotransferase reductase H O 3-phosphoglycerate H +NCH 2 dihydrobiopterin + 3 2 NADPH+H H2O – CH CH COO 2+ phosphoglycerate phosphatase glycine 2 Mg mutase + NH – 3 Pi COO 5 10 COO- N ,N -methylene H +NCH THF 3 HCOPO 2- serine CH 3 – hydroxymethyl 2 COO– COO transferase OH – CH OH COO 2 + tyrosine 2-phosphoglycerate H +NCH H NCH THF 3 3 α-ketoglutarate aspartate tyrosine CH CH OH enolase 2 2 aminotransferase α-ketoglutarate glutamate aspartate Mg2+ aminotransferase H O SH serine 4-hydroxyphenylpyruvate glutamate 2 GTPGDP CO – cysteine O2 COO– 2 COO dioxygenase O 2– 2 CO COPO dioxygenase dehydratase 2 C O 3 phosphoenolpyruvate H2O – carboxykinase homogentisate H C COO CH + 2 2 cysteine sulphinate NH O 4 2 1,2 dioxygenase oxaloacetate phosphoenolpyruvate α-ketoglutarate pyruvate + ADP aminotransferase NADH+H malate kinase 4-maleylacetoacetate glutamate dehydrogenase Mg2+ K+ NAD+ ATP α-ketoglutarate 2– H O 3-sulphinylpyruvate - - – SO3 2 fumarylacetoacetate COO COO glutamate COO H2O H2O fumarylacetoacetase CHOH H +NCH C O spontaneous 3 – alanine fumarate H C COO CH aminotransferase CH fumarase 2 3 3 acetoacetate malate alanine pyruvate

oxidised by dicarboxylate pyruvate extrahepatic tissues carrier carrier 2-phosphoglycerate CoASH + ADP ATP NAD thiamine PP kinase pyruvate dehydrogenase pyruvate carboxylase lipoate ATP (biotin) riboflavin NADH+H+ glycerate CO glycine ADP+Pi 2 NAD+ dehydrogenase HCO – O + 3 NADH+H N5,N10-methylene H CSC CoA 3-hydroxypyruvate THF 3 serine alanine hydroxymethyl acetyl CoA serine-pyruvate transferase – NAD+ NADH+H+ – aminotransferase COO COO CH COO– 2 pyruvate THF CHOH C O HOC COO– – malate citrate serine H C COO dehydrogenase H C COO– synthase – aconitase H2O 2 2 H O CoA H C COO 2 2 + malate oxaloacetate NAD glycine cleavage enzyme citrate H O [cis-aconitate] + or glycine synthase glutamate 2 NADH+H fumarase aspartate aconitase + H O aminotransferase NH4 2 α-ketoglutarate H2O – – THF HCCOO – – CH COO COO glutamine COO 2 5 10 – N ,N -methylene –OOCCH glutamate HC COO THF H +NCH H +NCH 3 3 – fumarate HOCH COO CO2 CH synthetase CH 2 2 ATP AMP+PP isocitrate COO– i CONH FADH 2 2 succinate isocitrate dehydrogenase dehydrogenase FAD aspartate asparagine 2+ Mg NAD+ – – CH COO + CH COO – 2 NADH+H 2 succinyl CoA CH COO α-ketoglutarate 2 CO2 CH COO– synthetase dehydrogenase CH 2 2 citrulline CH2 succinate – P OCCOO 2ATP i OCSCoA 2ADP+Pi ornithine CoASH GTP GDP+P NAD+ CoASH α-ketoglutarate transcarbamoylase i CO2 NADH succinyl CoA H+ + + carbamoyl NAD(P)H+H NH4 ATP carbamoyl phosphate phosphate O glutamate dehydrogenase synthetase urea 2 – + H O HCO H O NAD(P) 2 3 Mitochondrion 2 ADP F1 glutamate cycle F0

IV proline oxygenase C FADH2 FAD

aspartate ATP reductase pyrolline-5-carboxylate (P5C) synthetase AMP+PP NADH i – spontaneous + glutamate H+ – – + COO + NADPH NAD CH COO COO argininosuccinate NADP + γ-semialdehyde 2 N H dehydrogenase H glutamate CH H +NCH lyase 2 2 3 fumarate γ-semialdehyde + – P5C synthetase H N CH COO (CH ) – proline glutamate 3 2 3 COO aminotransferase ADP NADP+ NADPH ATP + glutamate + -ketoglutarate P H NH H NCH α i 2 3 ornithine ornithine (CH ) 2 3 5 N -formimino-THF glutamate + arginase NH NH H O H O formiminotransferase – 4 2 2 THF urea CH CH COO C NH 2 2 +NH urocanate 4-imidazolone- FIGLU NNH 3 +NH histidase hydratase 5-propionate imidazoline (N-formiminoglutamate) 2 histidine propionase arginine

0002858194.indd 134 11/26/2016 10:23:34 AM