Nutritional Biochemistry of the Vitamins

by David A. Bender

• ISBN13: 9780521803885
• ISBN10: 0521803888
• Edition: 2nd
• Format: Hardcover
• Copyright: 2003-09-18
• Publisher: Cambridge University Press

Summary

The vitamins are a chemically disparate group of compounds whose only common feature is that they are dietary essentials that are required in small amounts for the normal functioning of the body and maintenance of metabolic integrity. Metabolically they have diverse function, as coenzymes, hormones, antioxidants, mediators of cell signaling and regulators of cell and tissue growth and differentiation. This book, first published in 2003, explores the known biochemical functions of the vitamins, the extent to which we can explain the effects of deficiency or excess and the scientific basis for reference intakes for the prevention of deficiency and promotion of optimum health and well-being. It also highlights areas where our knowledge is lacking and further research is required. It provides a compact and authoritative reference volume of value to students and specialists alike in the field of nutritional biochemistry, and indeed all who are concerned with vitamin nutrition, deficiency and metabolism.

Table of Contents

List of Figures	xvii
List of Tables	xxi
Preface	xxiii
1 The Vitamins	1	(29)
1.1 Definition and Nomenclature of the Vitamins	2	(8)
1.1.1 Methods of Analysis and Units of Activity	6	(2)
1.1.2 Biological Availability	8	(2)
1.2 Vitamin Requirements and Reference Intakes	10	(20)
1.2.1 Criteria of Vitamin Adequacy and the Stages of Development of Deficiency	10	(2)
1.2.2 Assessment of Vitamin Nutritional Status	12	(5)
1.2.3 Determination of Requirements	17	(2)
1.2.3.1 Population Studies of Intake	17	(1)
1.2.3.2 Depletion/Repletion Studies	18	(1)
1.2.3.3 Replacement of Metabolic Losses	18	(1)
1.2.3.4 Studies in Patients Maintained on Total Parenteral Nutrition	19	(1)
1.2.4 Reference Intakes of Vitamins	19	(12)
1.2.4.1 Adequate Intake	23	(1)
1.2.4.2 Reference Intakes for Infants and Children	23	(1)
1.2.4.3 Tolerable Upper Levels of Intake	24	(3)
1.2.4.4 Reference Intake Figures for Food Labeling	27	(3)
2 Vitamin A: Retinoids and Carotenoids	30	(47)
2.1 Vitamin A Vitamers and Units of Activity	31	(4)
2.1.1 Retinoids	31	(2)
2.1.2 Carotenoids	33	(2)
2.1.3 International Units and Retinol Equivalents	35	(1)
2.2 Absorption and Metabolism of Vitamin A and Carotenoids	35	(14)
2.2.1 Absorption and Metabolism of Retinol and Retinoic Acid	35	(5)
2.2.1.1 Liver Storage and Release of Retinol	36	(2)
2.2.1.2 Metabolism of Retinoic Acid	38	(1)
2.2.1.3 Retinoyl Glucuronide and Other Metabolites	39	(1)
2.2.2 Absorption and Metabolism of Carotenoids	40	(5)
2.2.2.1 Carotene Dioxygenase	41	(1)
2.2.2.2 Limited Activity of Carotene Dioxygenase	42	(1)
2.2.2.3 The Reaction Specificity of Carotene Dioxygenase	43	(2)
2.2.3 Plasma Retinol Binding Protein (RBP)	45	(2)
2.2.4 Cellular Retinoid Binding Proteins CRBPs and CRABPs	47	(2)
2.3 Metabolic Functions of Vitamin A	49	(12)
2.3.1 Retinol and Retinaldehyde in the Visual Cycle	49	(5)
2.3.2 Genomic Actions of Retinoic Acid	54	(4)
2.3.2.1 Retinoid Receptors and Response Elements	55	(3)
2.3.3 Nongenomic Actions of Retinoids	58	(3)
2.3.3.1 Retinoylation of Proteins	58	(2)
2.3.3.2 Retinoids in Transmembrane Signaling	60	(1)
2.4 Vitamin A Deficiency (Xerophthalmia)	61	(5)
2.4.1 Assessment of Vitamin A Nutritional Status	64	(2)
2.4.1.1 Plasma Concentrations of Retinol and β-Carotene	64	(1)
2.4.1.2 Plasma Retinol Binding Protein	65	(1)
2.4.1.3 The Relative Dose Response (RDR) Test	66	(1)
2.4.1.4 Conjunctival Impression Cytology	66	(1)
2.5 Vitamin A Requirements and Reference Intakes	66	(11)
2.5.1 Toxicity of Vitamin A	68	(3)
2.5.1.1 Teratogenicity of Retinoids	70	(1)
2.5.2 Pharmacological Uses of Vitamin A, Retinoids, and Carotenoids	71	(8)
2.5.2.1 Retinoids in Cancer Prevention and Treatment	71	(1)
2.5.2.2 Retinoids in Dermatology	72	(1)
2.5.2.3 Carotene	72	(5)
3 Vitamin D	77	(32)
3.1 Vitamin D Vitamers, Nomenclature, and Units of Activity	78	(1)
3.2 Metabolism of Vitamin D	79	(10)
3.2.1 Photosynthesis of Cholecalciferol in the Skin	80	(2)
3.2.2 Dietary Vitamin D	82	(1)
3.2.3 25-Hydroxylation of Cholecalciferol	83	(2)
3.2.4 Calcidiol la-Hydroxylase	85	(1)
3.2.5 Calcidiol 24-Hydroxylase	85	(1)
3.2.6 Inactivation and Excretion of Calcitriol	86	(1)
3.2.7 Plasma Vitamin D Binding Protein (Gc-Globulin)	87	(1)
3.2.8 Regulation of Vitamin D Metabolism	87	(2)
3.2.8.1 Calcitriol	88	(1)
3.2.8.2 Parathyroid Hormone	88	(1)
3.2.8.3 Calcitonin	88	(1)
3.2.8.4 Plasma Concentrations of Calcium and Phosphate	89	(1)
3.3 Metabolic Functions of Vitamin D	89	(9)
3.3.1 Nuclear Vitamin D Receptors	91	(1)
3.3.2 Nongenomic Responses to Vitamin D	92	(1)
3.3.3 Stimulation of Intestinal Calcium and Phosphate Absorption	93	(1)
3.3.3.1 Induction of Calbindin-D	93	(1)
3.3.4 Stimulation of Renal Calcium Reabsorption	94	(1)
3.3.5 The Role of Calcitriol in Bone Metabolism	94	(2)
3.3.6 Cell Differentiation, Proliferation, and Apoptosis	96	(1)
3.3.7 Other Functions of Calcitriol	97	(1)
3.3.7.1 Endocrine Glands	98	(1)
3.3.7.2 The Immune System	98	(1)
3.4 Vitamin D Deficiency- Rickets and Osteomalacia	98	(5)
3.4.1 Nonnutritional Rickets and Osteomalacia	99	(1)
3.4.2 Vitamin D-Resistant Rickets	100	(1)
3.4.3 Osteoporosis	101	(3)
3.4.3.1 Glucocorticoid-Induced Osteoporosis	102	(1)
3.5 Assessment of Vitamin D Status	103	(1)
3.6 Requirements and Reference Intakes	104	(5)
3.6.1 Toxicity of Vitamin D	105	(1)
3.6.2 Pharmacological Uses of Vitamin D	106	(3)
4 Vitamin E: Tocopherols and Tocotrienols	109	(22)
4.1 Vitamin E Vitamers and Units of Activity	109	(4)
4.2 Metabolism of Vitamin E	113	(2)
4.3 Metabolic Functions of Vitamin E	115	(7)
4.3.1 Antioxidant Functions of Vitamin E	116	(4)
4.3.1.1 Prooxidant Actions of Vitamin E	118	(1)
4.3.1.2 Reaction of Tocopherol with Peroxynitrite	119	(1)
4.3.2 Nutritional Interactions Between Selenium and Vitamin E	120	(1)
4.3.3 Functions of Vitamin E in Cell Signaling	121	(1)
4.4 Vitamin E Deficiency	122	(3)
4.4.1 Vitamin E Deficiency in Experimental Animals	122	(3)
4.4.2 Human Vitamin E Deficiency	125	(1)
4.5 Assessment of Vitamin E Nutritional Status	125	(2)
4.6 Requirements and Reference Intakes	127	(4)
4.6.1 Upper Levels of Intake	128	(1)
4.6.2 Pharmacological Uses of Vitamin E	128	(5)
4.6.2.1 Vitamin E and Cancer	129	(1)
4.6.2.2 Vitamin E and Cardiovascular Disease	129	(1)
4.6.2.3 Vitamin E and Cataracts	129	(1)
4.6.2.4 Vitamin E and Neurodegenerative Diseases	129	(2)
5 Vitamin K	131	(17)
5.1 Vitamin K Vitamers	132	(1)
5.2 Metabolism of Vitamin K	133	(2)
5.2.1 Bacterial Biosynthesis of Menaquinones	135	(1)
5.3 The Metabolic Functions of Vitamin K	135	(7)
5.3.1 The Vitamin K-Dependent Carboxylase	136	(3)
5.3.2 Vitamin K-Dependent Proteins in Blood Clotting	139	(2)
5.3.3 Osteocalcin and Matrix Gla Protein	141	(1)
5.3.4 Vitamin K-Dependent Proteins in Cell Signaling - Gash	142	(1)
5.4 Vitamin K Deficiency	142	(1)
5.4.1 Vitamin K Deficiency Bleeding in Infancy	143	(1)
5.5 Assessment of Vitamin K Nutritional Status	143	(2)
5.6 Vitamin K Requirements and Reference Intakes	145	(3)
5.6.1 Upper Levels of Intake	145	(1)
5.6.2 Pharmacological Uses of Vitamin K	146	(2)
6 Vitamin B, - Thiamin	148	(24)
6.1 Thiamin Vitamers and Antagonists	148	(2)
6.2 Metabolism of Thiamin	150	(3)
6.2.1 Biosynthesis of Thiamin	153	(1)
6.3 Metabolic Functions of Thiamin	153	(8)
6.3.1 Thiamin Diphosphate in the Oxidative Decarboxylation of Oxoacids	154	(5)
6.3.1.1 Regulation of Pyruvate Dehydrogenase Activity	155	(1)
6.3.1.2 Thiamin-Responsive Pyruvate Dehydrogenase Deficiency	156	(1)
6.3.1.3 2-Oxoglutarate Dehydrogenase and the y-Aminobutyric Acid (GABA) Shunt	156	(2)
6.3.1.4 Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease	158	(1)
6.3.2 Transketolase	159	(1)
6.3.3 The Neuronal Function of Thiamin Triphosphate	159	(2)
6.4 Thiamin Deficiency	161	(6)
6.4.1 Dry Beriberi	161	(1)
6.4.2 Wet Beriberi	162	(1)
6.4.3 Acute Pernicious (Fulminating) Beriberi - Shoshin Beriberi	162	(1)
6.4.4 The Wernicke-Korsakoff Syndrome	163	(1)
6.4.5 Effects of Thiamin Deficiency on Carbohydrate Metabolism	164	(1)
6.4.6 Effects of Thiamin Deficiency on Neurotransmitters	165	(1)
6.4.6.1 Acetylcholine	165	(1)
6.4.6.2 5-Hydroxytryptamine	165	(1)
6.4.7 Thiaminases and Thiamin Antagonists	166	(1)
6.5 Assessment of Thiamin Nutritional Status	167	(2)
6.5.1 Urinary Excretion of Thiamin and Thiochrome	167	(1)
6.5.2 Blood Concentration of Thiamin	167	(1)
6.5.3 Erythrocyte Transketolase Activation	168	(1)
6.6 Thiamin Requirements and Reference Intakes	169	(3)
6.6.1 Upper Levels of Thiamin Intake	169	(1)
6.6.2 Pharmacological Uses of Thiamin	169	(3)
7 Vitamin B2 - Riboflavin	172	(28)
7.1 Riboflavin and the Flavin Coenzymes	172	(3)
7.2 The Metabolism of Riboflavin	175	(8)
7.2.1 Absorption, Tissue Uptake, and Coenzyme Synthesis	175	(2)
7.2.2 Riboflavin Binding Protein	177	(1)
7.2.3 Riboflavin Homeostasis	178	(1)
7.2.4 The Effect of Thyroid Hormones on Riboflavin Metabolism	178	(1)
7.2.5 Catabolism and Excretion of Riboflavin	179	(2)
7.2.6 Biosynthesis of Riboflavin	181	(2)
7.3 Metabolic Functions of Riboflavin	183	(7)
7.3.1 The Flavin Coenzymes: FAD and Riboflavin Phosphate	183	(1)
7.3.2 Single-Electron-Transferring Flavoproteins	184	(1)
7.3.3 Two-Electron-Transferring Flavoprotein Dehydrogenases	185	(1)
7.3.4 Nicotinamide Nucleotide Disulfide Oxidoreductases	185	(1)
7.3.5 Flavin Oxidases	186	(1)
7.3.6 NADPH Oxidase, the Respiratory Burst Oxidase	187	(1)
7.3.7 Molybdenum-Containing Flavoprotein Hydroxylases	188	(1)
7.3.8 Flavin Mixed-Function Oxidases (Hydroxylases)	189	(1)
7.3.9 The Role of Riboflavin in the Cryptochromes	190	(1)
7.4 Riboflavin Deficiency	190	(6)
7.4.1 Impairment of Lipid Metabolism in Riboflavin Deficiency	191	(1)
7.4.2 Resistance to Malaria in Riboflavin Deficiency	192	(1)
7.4.3 Secondary Nutrient Deficiencies in Riboflavin Deficiency	193	(1)
7.4.4 Iatrogenic Riboflavin Deficiency	194	(2)
7.5 Assessment of Riboflavin Nutritional Status	196	(1)
7.5.1 Urinary Excretion of Riboflavin	196	(1)
7.5.2 Erythrocyte Glutathione Reductase (EGR) Activation Coefficient	197	(1)
7.6 Riboflavin Requirements and Reference Intakes	197	(1)
7.7 Pharmacological Uses of Riboflavin	198	(2)
8 Niacin	200	(32)
8.1 Niacin Vitamers and Nomenclature	201	(2)
8.2 Niacin Metabolism	203	(5)
8.2.1 Digestion and Absorption	203	(1)
8.2.1.1 Unavailable Niacin in Cereals	203	(1)
8.2.2 Synthesis of the Nicotinamide Nucleotide Coenzymes	203	(2)
8.2.3 Catabolism of NADP)	205	(1)
8.2.4 Urinary Excretion of Niacin Metabolites	206	(2)
8.3 The Synthesis of Nicotinamide Nucleotides from Tryptophan	208	(6)
8.3.1 Picolinate Carboxylase and Nonenzymic Cyclization to Quinolinic Acid	210	(1)
8.3.2 Tryptophan Dioxygenase	211	(1)
8.3.2.1 Saturation of Tryptophan Dioxygenase with Its Heme Cofactor	211	(1)
8.3.2.2 Induction of Tryptophan Dioxygenase by Glucocorticoid Hormones	211	(1)
8.3.2.3 Induction Tryptophan Dioxygenase by Glucagon	212	(1)
8.3.2.4 Repression and Inhibition of Tryptophan Dioxygenase by Nicotinamide Nucleotides	212	(1)
8.3.3 Kynurenine Hydroxylase and Kynureninase	212	(2)
8.3.3.1 Kynurenine Hydroxylase	213	(1)
8.3.3.2 Kynureninase	213	(1)
8.4 Metabolic Functions of Niacin	214	(7)
8.4.1 The Redox Function of NAD(P)	214	(1)
8.4.1.1 Use of NAD(P) in Enzyme Assays	215	(1)
8.4.2 ADP-Ribosyltransferases	215	(2)
8.4.3 Poly(ADP-ribose) Polymerases	217	(2)
8.4.4 cADP-Ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)	219	(2)
8.5 Pellagra - A Disease of Tryptophan and Niacin Deficiency	221	(4)
8.5.1 Other Nutrient Deficiencies in the Etiology of Pellagra	222	(1)
8.5.2 Possible Pellagragenic Toxins	223	(1)
8.5.3 The Pellagragenic Effect of Excess Dietary Leucine	223	(1)
8.5.4 Inborn Errors of Tryptophan Metabolism	224	(1)
8.5.5 Carcinoid Syndrome	224	(1)
8.5.6 Drug-Induced Pellagra	225	(1)
8.6 Assessment of Niacin Nutritional Status	225	(2)
8.6.1 Tissue and Whole Blood Concentrations of Nicotinamide Nucleotides	226	(1)
8.6.2 Urinary Excretion of N1-Methyl Nicotinamide and Methyl Pyridone Carboxamide	226	(1)
8.7 Niacin Requirements and Reference Intakes	227	(2)
8.7.1 Upper Levels of Niacin Intake	228	(1)
8.8 Pharmacological Uses of Niacin	229	(3)
9 Vitamin B6	232	(38)
9.1 Vitamin B6 Vitamers and Nomenclature	233	(1)
9.2 Metabolism of Vitamin B6	234	(2)
9.2.1 Muscle Pyridoxal Phosphate	236	(1)
9.2.2 Biosynthesis of Vitamin B6	236	(1)
9.3 Metabolic Functions of Vitamin B6	236	(10)
9.3.1 Pyridoxal Phosphate in Amino Acid Metabolism	237	(7)
9.3.1.1 a-Decarboxylation of Amino Acids	239	(2)
9.3.1.2 Racemization of the Amino Acid Substrate	241	(1)
9.3.1.3 Transamination of Amino Acids (Aminotransferase Reactions)	241	(1)
9.3.1.4 Steps in the Transaminase Reaction	242	(1)
9.3.1.5 Transamination Reactions of Other Pyridoxal Phosphate Enzymes	243	(1)
9.3.1.6 Transamination and Oxidative Deamination Catalyzed by Dihydroxyphenylalanine (DOPA) Decarboxylase	243	(1)
9.3.1.7 Side-Chain Elimination and Replacement Reactions	244	(1)
9.3.2 The Role of Pyridoxal Phosphate in Glycogen Phosphorylase	244	(1)
9.3.3 The Role of Pyridoxal Phosphate in Steroid Hormone Action and Gene Expression	245	(1)
9.4 Vitamin B6 Deficiency	246	(4)
9.4.1 Enzyme Responses to Vitamin B6 Deficiency	247	(2)
9.4.2 Drug-Induced Vitamin B6 Deficiency	249	(1)
9.4.3 Vitamin B6 Dependency Syndromes	250	(1)
9.5 The Assessment of Vitamin B6 Nutritional Status	250	(6)
9.5.1 Plasma Concentrations of Vitamin B6	251	(1)
9.5.2 Urinary Excretion of Vitamin B6 and 4-Pyridoxác Acid	251	(1)
9.5.3 Coenzyme Saturation of Transaminases	252	(1)
9.5.4 The Tryptophan Load Test	252	(3)
9.5.4.1 Artifacts in the Tryptophan Load Test Associated with Increased Tryptophan Dioxygenase Activity	253	(1)
9.5.4.2 Estrogens and Apparent Vitamin B6 Nutritional Status	254	(1)
9.5.5 The Methionine Load Test	255	(1)
9.6 Vitamin B6 Requirements and Reference Intakes	256	(5)
9.6.1 Vitamin B6 Requirements Estimated from Metabolic Turnover	256	(1)
9.6.2 Vitamin B6 Requirements Estimated from Depletion! Repletion Studies	257	(2)
9.6.3 Vitamin B6 Requirements of Infants	259	(1)
9.6.4 Toxicity of Vitamin B6	259	(2)
9.6.4.1 Upper Levels of Vitamin B6 Intake	260	(1)
9.7 Pharmacological Uses of Vitamin B6	261	(4)
9.7.1 Vitamin B6 and Hyperhomocysteinemia	261	(1)
9.7.2 Vitamin B6 and the Premenstrual Syndrome	262	(1)
9.7.3 Impaired Glucose Tolerance	262	(1)
9.7.4 Vitamin B6 for Prevention of the Complications of Diabetes Mellitus	263	(1)
9.7.5 Vitamin B6 for the Treatment of Depression	264	(1)
9.7.6 Antihypertensive Actions of Vitamin B6	264	(1)
9.8 Other Carbonyl Catalysts	265	(5)
9.8.1 Pyruvoyl Enzymes	266	(1)
9.8.2 Pyrroloquinoline Quinone (PQQ) and Tryptophan Tryptophylquinone (TTQ)	266	(2)
9.8.3 Quinone Catalysts in Mammalian Enzymes	268	(2)
10 Folate and Other Pterins and Vitamin B12	270	(54)
10.1 Folate Vitamers and Dietary Folate Equivalents	271	(1)
10.1.1 Dietary Folate Equivalents	271	(2)
10.2 Metabolism of Folates	273	(6)
10.2.1 Digestion and Absorption of Folates	273	(1)
10.2.2 Tissue Uptake and Metabolism of Folate	274	(2)
10.2.2.1 Poly-y-glutamylation of Folate	275	(1)
10.2.3 Catabolism and Excretion of Folate	276	(1)
10.2.4 Biosynthesis of Pterins	276	(3)
10.3 Metabolic Functions of Folate	279	(15)
10.3.1 Sources of Substituted Folates	279	(4)
10.3.1.1 Serine Hydroxymethyltransferase	279	(2)
10.3.1.2 Histidine Catabolism	281	(2)
10.3.1.3 Other Sources of One-Carbon Substituted Folates	283	(1)
10.3.2 Interconversion of Substituted Folates	283	(3)
10.3.2.1 Methylene-Tetrahydrofolate Reductase	284	(2)
10.3.2.2 Disposal of Surplus One-Carbon Fragments	286	(1)
10.3.3 Utilization of One-Carbon Substituted Folates	286	(3)
10.3.3.1 Thymidylate Synthetase and Dihydrofolate Reductase	287	(1)
10.3.3.2 Dihydrofolate Reductase Inhibitors	288	(1)
10.3.3.3 The dUMP Suppression Test	289	(1)
10.3.4 The Role of Folate in Methionine Metabolism	289	(5)
10.3.4.1 The Methyl Folate Trap Hypothesis	291	(1)
10.3.4.2 Hyperhomocysteinemia and Cardiovascular Disease	292	(2)
10.4 Tetrahydrobiopterin	294	(3)
10.4.1 The Role of Tetrahydrobiopterin in Aromatic Amino Acid Hydroxylases	294	(2)
10.4.2 The Role of Tetrahydrobiopterin in Nitric Oxide Synthase	296	(1)
10.5 Molybdopterin	297	(1)
10.6 Vitamin B12 Vitamers and Nomenclature	298	(2)
10.7 Metabolism of Vitamin B12	300	(3)
10.7.1 Digestion and Absorption of Vitamin B12	300	(1)
10.7.2 Plasma Vitamin B12 Binding Proteins and Tissue Uptake	301	(2)
10.7.3 Bacterial Biosynthesis of Vitamin B12	303	(1)
10.8 Metabolic Functions of Vitamin B12	303	(4)
10.8.1 Methionine Synthetase	304	(1)
10.8.2 Methylmalonyl CoA Mutase	305	(1)
10.8.3 Leucine Aminomutase	306	(1)
10.9 Deficiency of Folic Acid and Vitamin B12	307	(6)
10.9.1 Megaloblastic Anemia	308	(1)
10.9.2 Pernicious Anemia	308	(1)
10.9.3 Neurological Degeneration in Vitamin B12 Deficiency	309	(1)
10.9.4 Folate Deficiency and Neural Tube Defects	310	(1)
10.9.5 Folate Deficiency and Cancer Risk	311	(1)
10.9.6 Drug-Induced Folate Deficiency	312	(1)
10.9.7 Drug-Induced Vitamin B12 Deficiency	313	(1)
10.10 Assessment of Folate and Vitamin B12 Nutritional Status	313	(5)
10.10.1 Plasma and Erythrocyte Concentrations of Folate and Vitamin B12	314	(1)
10.10.2 The Schilling Test for Vitamin B12 Absorption	315	(1)
10.10.3 Methylmalonic Aciduria and Methylmalonic Acidemia	316	(1)
10.10.4 Histidine Metabolism - the FIGLU Test	316	(1)
10.10.5 The dUMP Suppression Test	317	(1)
10.11 Folate and Vitamin B12 Requirements and Reference Intakes	318	(3)
10.11.1 Folate Requirements	318	(1)
10.11.2 Vitamin B12 Requirements	318	(1)
10.11.3 Upper Levels of Folate Intake	319	(2)
10.12 Pharmacological Uses of Folate and Vitamin B12	321	(3)
11 Biotin (Vitamin H)	324	(21)
11.1 Metabolism of Biotin	324	(5)
11.1.1 Bacterial Synthesis of Biotin	327	(2)
11.1.1.1 The Importance of Intestinal Bacterial Synthesis of Biotin	329	(1)
11.2 The Metabolic Functions of Biotin	329	(8)
11.2.1 The Role of Biotin in Carboxylation Reactions	330	(2)
11.2.1.1 Acetyl CoA Carboxylase	330	(1)
11.2.1.2 Pyruvate Carboxylase	331	(1)
11.2.1.3 Propionyl CoA Carboxylase	331	(1)
11.2.1.4 Methylcrotonyl CoA Carboxylase	332	(1)
11.2.2 Holocarboxylase Synthetase	332	(2)
11.2.2.1 Holocarboxylase Synthetase Deficiency	332	(2)
11.2.3 Biotinidase	334	(1)
11.2.3.1 Biotinidase Deficiency	335	(1)
11.2.4 Enzyme Induction by Biotin	335	(1)
11.2.5 Biotin in Regulation of the Cell Cycle	336	(1)
11.3 Biotin Deficiency	337	(3)
11.3.1 Metabolic Consequences of Biotin Deficiency	338	(2)
11.3.1.1 Glucose Homeostasis in Biotin Deficiency	338	(1)
11.3.1.2 Fatty Liver and Kidney Syndrome in Biotin-Deficient Chicks	338	(1)
11.3.1.3 Cot Death	339	(1)
11.3.2 Biotin Deficiency In Pregnancy	340	(1)
11.4 Assessment of Biotin Nutritional Status	340	(1)
11.5 Biotin Requirements	341	(1)
11.6 Avidin	341	(4)
12 Pantothenic Acid	345	(12)
12.1 Pantothenic Acid Vitamers	345	(1)
12.2 Metabolism of Pantothenic Acid	346	(6)
12.2.1 The Formation of CoA from Pantothenic Acid	348	(2)
12.2.1.1 Metabolic Control of CoA Synthesis	349	(1)
12.2.2 Catabolism of CoA	350	(1)
12.2.3 The Formation and Turnover of ACP	350	(1)
12.2.4 Biosynthesis of Pantothenic Acid	351	(1)
12.3 Metabolic Functions of Pantothenic Acid	352	(1)
12.4 Pantothenic Acid Deficiency	353	(2)
12.4.1 Pantothenic Acid Deficiency in Experimental Animals	353	(1)
12.4.2 Human Pantothenic Acid Deficiency - The Burning Foot Syndrome	354	(1)
12.5 Assessment of Pantothenic Acid Nutritional Status	355	(1)
12.6 Pantothenic Acid Requirements	355	(1)
12.7 Pharmacological Uses of Pantothenic Acid	356	(1)
13 Vitamin C (Ascorbic Acid)	357	(28)
13.1 Vitamin C Vitamers and Nomenclature	358	(1)
13.1.1 Assay of Vitamin C	359	(1)
13.2 Metabolism of Vitamin C	359	(5)
13.2.1 Intestinal Absorption and Secretion of Vitamin C	361	(1)
13.2.2 Tissue Uptake of Vitamin C	361	(1)
13.2.3 Oxidation and Reduction of Ascorbate	362	(1)
13.2.4 Metabolism and Excretion of Ascorbate	363	(1)
13.3 Metabolic Functions of Vitamin C	364	(8)
13.3.1 Dopamine β-Hydroxylase	365	(1)
13.3.2 Peptidyl Glycine Hydroxylase (Peptide a-Amidase)	366	(1)
13.3.3 2-Oxoglutarate-Linked Iron-Containing Hydroxylases	367	(2)
13.3.4 Stimulation of Enzyme Activity by Ascorbate In Vitro	369	(1)
13.3.5 The Role of Ascorbate in Iron Absorption and Metabolism	369	(1)
13.3.6 Inhibition of Nitrosamine Formation by Ascorbate	370	(1)
13.3.7 Pro- and Antioxidant Roles of Ascorbate	371	(1)
13.3.7.1 Reduction of the Vitamin E Radical by Ascorbate	371	(1)
13.3.8 Ascorbic Acid in Xenobiotic and Cholesterol Metabolism	371	(1)
13.4 Vitamin C Deficiency - Scurvy	372	(2)
13.4.1 Anemia in Scurvy	373	(1)
13.5 Assessment of Vitamin C Status	374	(2)
13.5.1 Urinary Excretion of Vitamin C and Saturation Testing	374	(1)
13.5.2 Plasma and Leukocyte Concentrations of Ascorbate	374	(2)
13.5.3 Markers of DNA Oxidative Damage	376	(1)
13.6 Vitamin C Requirements and Reference Intakes	376	(6)
13.6.1 The Minimum Requirement for Vitamin C	376	(2)
13.6.2 Requirements Estimated from the Plasma and Leukocyte Concentrations of Ascorbate	378	(1)
13.6.3 Requirements Estimated from Maintenance of the Body Pool of Ascorbate	378	(1)
13.6.4 Higher Recommendations	379	(1)
13.6.4.1 The Effect of Smoking on Vitamin C Requirements	380	(1)
13.6.5 Safety and Upper Levels of Intake of Vitamin C	380	(2)
13.6.5.1 Renal Stones	380	(1)
13.6.5.2 False Results in Urine Glucose Testing	381	(1)
13.6.5.3 Rebound Scurvy	381	(1)
13.6.5.4 Ascorbate and Iron Overload	382	(1)
13.7 Pharmacological Uses of Vitamin C	382	(3)
13.7.1 Vitamin C in Cancer Prevention and Therapy	382	(1)
13.7.2 Vitamin C in Cardiovascular Disease	383	(1)
13.7.3 Vitamin C and the Common Cold	383	(2)
14 Marginal Compounds and Phytonutrients	385	(24)
14.1 Carnitine	385	(4)
14.1.1 Biosynthesis and Metabolism of Carnitine	386	(2)
14.1.2 The Possible Essentiality of Carnitine	388	(1)
14.1.3 Carnitine as an Ergogenic Aid	388	(1)
14.2 Choline	389	(3)
14.2.1 Biosynthesis and Metabolism of Choline	389	(2)
14.2.2 The Possible Essentiality of Choline	391	(1)
14.3 Creatine	392	(1)
14.4 Inositol	393	(3)
14.4.1 Phosphatidylinositol in Transmembrane Signaling	394	(1)
14.4.2 The Possible Essentiality of Inositol	394	(2)
14.5 Taurine	396	(4)
14.5.1 Biosynthesis of Taurine	396	(2)
14.5.2 Metabolic Functions of Taurine	398	(1)
14.5.2.1 Taurine Conjugation of Bile Acids	398	(1)
14.5.2.2 Taurine in the Central Nervous System	398	(1)
14.5.2.3 Taurine and Heart Muscle	399	(1)
14.5.3 The Possible Essentiality of Taurine	399	(1)
14.6 Ubiquinone (Coenzyme Q)	400	(1)
14.7 Phytonutrients: Potentially Protective Compounds in Plant Foods	401	(8)
14.7.1 Allyl Sulfur Compounds	401	(1)
14.7.2 Flavonoids and Polyphenols	402	(1)
14.7.3 Glucosinolates	403	(1)
14.7.4 Phytoestrogens	404	(5)
Bibliography	409	(54)
Index	463