Nutritional Biochemistry of the Vitamins

Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
List of Figures......Page 19
List of Tables......Page 23
Preface......Page 25
ONE The Vitamins......Page 27
1.1 DEFINITION AND NOMENCLATURE OF THE VITAMINS......Page 28
1.1.1 Methods of Analysis and Units of Activity......Page 32
1.1.2 Biological Availability......Page 34
1.2.1 Criteria of Vitamin Adequacy and the Stages of Development of Deficiency......Page 36
1.2.2 Assessment of Vitamin Nutritional Status......Page 38
1.2.3 Determination of Requirements......Page 43
1.2.4 Reference Intakes of Vitamins......Page 45
FURTHER READING......Page 54
TWO Vitamin A: Retinoids and Carotenoids......Page 56
2.1.1 Retinoids......Page 57
2.1.2 Carotenoids......Page 59
2.2.1 Absorption and Metabolism of Retinol and Retinoic Acid......Page 61
2.2.2 Absorption and Metabolism of Carotenoids......Page 66
2.2.3 Plasma Retinol Binding Protein (RBP)......Page 71
2.2.4 Cellular Retinoid Binding Proteins: CRBPs and CRABPs......Page 73
2.3.1 Retinol and Retinaldehyde in the Visual Cycle......Page 75
2.3.2 Genomic Actions of Retinoic Acid......Page 80
2.3.3 Nongenomic Actions of Retinoids......Page 84
2.4 VITAMIN A DEFICIENCY (XEROPHTHALMIA)......Page 87
2.4.1 Assessment of Vitamin Nutritional Status......Page 90
2.5 VITAMIN A REQUIREMENTS AND REFERENCE INTAKES......Page 92
2.5.1 Toxicity of Vitamin A......Page 94
2.5.2 Pharmacological Uses of Vitamin A, Retinoids, and Carotenoids......Page 97
FURTHER READING......Page 100
THREE Vitamin D......Page 103
3.1 VITAMIN D VITAMERS, NOMENCLATURE, AND UNITS OF ACTIVITY......Page 104
3.2 METABOLISM OF VITAMIN D......Page 105
3.2.1 Photosynthesis of Cholecalciferol in the Skin......Page 106
3.2.2 Dietary Vitamin D......Page 108
3.2.3 25-Hydroxylation of Cholecalciferol......Page 109
3.2.5 Calcidiol 24-Hydroxylase......Page 111
3.2.6 Inactivation and Excretion of Calcitriol......Page 112
3.2.8 Regulation of Vitamin D Metabolism......Page 113
3.3 METABOLIC FUNCTIONS OF VITAMIN D......Page 115
3.3.1 Nuclear Vitamin D Receptors......Page 117
3.3.2 Nongenomic Responses to Vitamin D......Page 118
3.3.3 Stimulation of Intestinal Calcium and Phosphate Absorption......Page 119
3.3.5 The Role of Calcitriol in Bone Metabolism......Page 120
3.3.6 Cell Differentiation, Proliferation, and Apoptosis......Page 122
3.3.7 Other Functions of Calcitriol......Page 123
3.4 VITAMIN D DEFICIENCY – RICKETS AND OSTEOMALACIA......Page 124
3.4.1 Nonnutritional Rickets and Osteomalacia......Page 125
3.4.2 Vitamin D-Resistant Rickets......Page 126
3.4.3 Osteoporosis......Page 127
3.5 ASSESSMENT OF VITAMIN D STATUS......Page 129
3.6 REQUIREMENTS AND REFERENCE INTAKES......Page 130
3.6.1 Toxicity of Vitamin D......Page 131
3.6.2 Pharmacological Uses of Vitamin D......Page 132
FURTHER READING......Page 133
4.1 VITAMIN E VITAMERS AND UNITS OF ACTIVITY......Page 135
4.2 METABOLISM OF VITAMIN E......Page 139
4.3 METABOLIC FUNCTIONS OF VITAMIN E......Page 141
4.3.1 Antioxidant Functions of Vitamin E......Page 142
4.3.2 Nutritional Interactions Between Selenium and Vitamin E......Page 146
4.3.3 Functions of Vitamin E in Cell Signaling......Page 147
4.4.1 Vitamin E Deficiency in Experimental Animals......Page 148
4.5 ASSESSMENT OF VITAMIN E NUTRITIONAL STATUS......Page 151
4.6 REQUIREMENTS AND REFERENCE INTAKES......Page 153
4.6.2 Pharmacological Uses of Vitamin E......Page 154
FURTHER READING......Page 156
FIVE Vitamin K......Page 157
5.1 VITAMIN K VITAMERS......Page 158
5.2 METABOLISM OF VITAMIN K......Page 159
5.3 THE METABOLIC FUNCTIONS OF VITAMIN K......Page 161
5.3.1 The Vitamin K-Dependent Carboxylase......Page 162
5.3.2 Vitamin K-Dependent Proteins in Blood Clotting......Page 165
5.3.3 Osteocalcin and Matrix Gla Protein......Page 167
5.4 VITAMIN K DEFICIENCY......Page 168
5.5 ASSESSMENT OF VITAMIN K NUTRITIONAL STATUS......Page 169
5.6.1 Upper Levels of Intake......Page 171
5.6.2 Pharmacological Uses of Vitamin K......Page 172
FURTHER READING......Page 173
6.1 THIAMIN VITAMERS AND ANTAGONISTS......Page 174
6.2 METABOLISM OF THIAMIN......Page 176
6.3 METABOLIC FUNCTIONS OF THIAMIN......Page 179
6.3.1 Thiamin Diphosphate in the Oxidative Decarboxylation of Oxo-acids......Page 180
6.3.3 The Neuronal Function of Thiamin Triphosphate......Page 185
6.4.1 Dry Beriberi......Page 187
6.4.3 Acute Pernicious (Fulminating) Beriberi – Shoshin Beriberi......Page 188
6.4.4 The Wernicke–Korsakoff Syndrome......Page 189
6.4.5 Effects of Thiamin Deficiency on Carbohydrate Metabolism......Page 190
6.4.6 Effects of Thiamin Deficiency on Neurotransmitters......Page 191
6.4.7 Thiaminases and Thiamin Antagonists......Page 192
6.5.2 Blood Concentration of Thiamin......Page 193
6.5.3 Erythrocyte Transketolase Activation......Page 194
6.6.2 Pharmacological Uses of Thiamin......Page 195
FURTHER READING......Page 196
7.1 RIBOFLAVIN AND THE FLAVIN COENZYMES......Page 198
7.2.1 Absorption, Tissue Uptake, and Coenzyme Synthesis......Page 201
7.2.2 Riboflavin Binding Protein......Page 203
7.2.4 The Effect of Thyroid Hormones on Riboflavin Metabolism......Page 204
7.2.5 Catabolism and Excretion of Riboflavin......Page 205
7.2.6 Biosynthesis of Riboflavin......Page 207
7.3.1 The Flavin Coenzymes: FAD and Riboflavin Phosphate......Page 209
7.3.2 Single-Electron–Transferring Flavoproteins......Page 210
7.3.4 Nicotinamide Nucleotide Disulfide Oxidoreductases......Page 211
7.3.5 Flavin Oxidases......Page 212
7.3.6 NADPH Oxidase, the Respiratory Burst Oxidase......Page 213
7.3.7 Molybdenum-Containing Flavoprotein Hydroxylases......Page 214
7.3.8 Flavin Mixed-Function Oxidases (Hydroxylases)......Page 215
7.3.9 The Role of Riboflavin in the Cryptochromes......Page 216
7.4.1 Impairment of Lipid Metabolism in Riboflavin Deficiency......Page 217
7.4.2 Resistance to Malaria in Riboflavin Deficiency......Page 218
7.4.3 Secondary Nutrient Deficiencies in Riboflavin Deficiency......Page 219
7.4.4 Iatrogenic Riboflavin Deficiency......Page 220
7.5.1 Urinary Excretion of Riboflavin......Page 222
7.6 RIBOFLAVIN REQUIREMENTS AND REFERENCE INTAKES......Page 223
7.7 PHARMACOLOGICAL USES OF RIBOFLAVIN......Page 224
FURTHER READING......Page 225
EIGHT Niacin......Page 226
8.1 NIACIN VITAMERS AND NOMENCLATURE......Page 227
8.2.2 Synthesis of the Nicotinamide Nucleotide Coenzymes......Page 229
8.2.3 Catabolism of NAD(P)......Page 231
8.2.4 Urinary Excretion of Niacin Metabolites......Page 232
8.3 THE SYNTHESIS OF NICOTINAMIDE NUCLEOTIDES FROM TRYPTOPHAN......Page 234
8.3.1 Picolinate Carboxylase and Nonenzymic Cyclization to Quinolinic Acid......Page 236
8.3.2 Tryptophan Dioxygenase......Page 237
8.3.3 Kynurenine Hydroxylase and Kynureninase......Page 238
8.4.1 The Redox Function of NAD(P)......Page 240
8.4.2 ADP-Ribosyltransferases......Page 241
8.4.3 Poly(ADP-ribose) Polymerases......Page 243
8.4.4 cADP-Ribose and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)......Page 245
8.5 PELLAGRA – A DISEASE OF TRYPTOPHAN AND NIACIN DEFICIENCY......Page 247
8.5.1 Other Nutrient Deficiencies in the Etiology of Pellagra......Page 248
8.5.3 The Pellagragenic Effect of Excess Dietary Leucine......Page 249
8.5.5 Carcinoid Syndrome......Page 250
8.6 ASSESSMENT OF NIACIN NUTRITIONAL STATUS......Page 251
8.6.2 Urinary Excretion of N -Methyl Nicotinamide and Methyl Pyridone Carboxamide......Page 252
8.7 NIACIN REQUIREMENTS AND REFERENCE INTAKES......Page 253
8.7.1 Upper Levels of Niacin Intake......Page 254
8.8 PHARMACOLOGICAL USES OF NIACIN......Page 255
FURTHER READING......Page 256
NINE Vitamin B......Page 258
9.1 VITAMIN B VITAMERS AND NOMENCLATURE......Page 259
9.2 METABOLISM OF VITAMIN B......Page 260
9.3 METABOLIC FUNCTIONS OF VITAMIN B......Page 262
9.3.1 Pyridoxal Phosphate in Amino Acid Metabolism......Page 263
9.3.2 The Role of Pyridoxal Phosphate in Glycogen Phosphorylase......Page 270
9.3.3 The Role of Pyridoxal Phosphate in Steroid Hormone Action and Gene Expression......Page 271
9.4 VITAMIN B DEFICIENCY......Page 272
9.4.1 Enzyme Responses to Vitamin B Deficiency......Page 273
9.4.2 Drug-Induced Vitamin B Deficiency......Page 275
9.5 THE ASSESSMENT OF VITAMIN B NUTRITIONAL STATUS......Page 276
9.5.2 Urinary Excretion of Vitamin B and 4-Pyridoxic Acid......Page 277
9.5.4 The Tryptophan Load Test......Page 278
9.5.5 The Methionine Load Test......Page 281
9.6.1 Vitamin B Requirements Estimated from Metabolic Turnover......Page 282
9.6.2 Vitamin B Requirements Estimated from Depletion/Repletion Studies......Page 283
9.6.4 Toxicity of Vitamin B......Page 285
9.7.1 Vitamin B and Hyperhomocysteinemia......Page 287
9.7.3 Impaired Glucose Tolerance......Page 288
9.7.4 Vitamin B for Prevention of the Complications of Diabetes Mellitus......Page 289
9.7.6 Antihypertensive Actions of Vitamin B......Page 290
9.8 OTHER CARBONYL CATALYSTS......Page 291
9.8.2 Pyrroloquinoline Quinone (PQQ) and Tryptophan Tryptophylquinone (TTQ)......Page 292
FURTHER READING......Page 294
TEN Folate and Other Pterins and Vitamin B......Page 296
10.1.1 Dietary Folate Equivalents......Page 297
10.2.1 Digestion and Absorption of Folates......Page 299
10.2.2 Tissue Uptake and Metabolism of Folate......Page 300
10.2.4 Biosynthesis of Pterins......Page 302
10.3.1 Sources of Substituted Folates......Page 305
10.3.2 Interconversion of Substituted Folates......Page 309
10.3.3 Utilization of One-Carbon Substituted Folates......Page 312
10.3.4 The Role of Folate in Methionine Metabolism......Page 315
10.4.1 The Role of Tetrahydrobiopterin in Aromatic Amino Acid Hydroxylases......Page 320
10.4.2 The Role of Tetrahydrobiopterin in Nitric Oxide Synthase......Page 322
10.5 MOLYBDOPTERIN......Page 323
10.6 VITAMIN B VITAMERS AND NOMENCLATURE......Page 324
10.7.1 Digestion and Absorption of Vitamin B......Page 326
10.7.2 Plasma Vitamin B Binding Proteins and Tissue Uptake......Page 327
10.8 METABOLIC FUNCTIONS OF VITAMIN B......Page 329
10.8.1 Methionine Synthetase......Page 330
10.8.2 Methylmalonyl CoA Mutase......Page 331
10.8.3 Leucine Aminomutase......Page 332
10.9 DEFICIENCY OF FOLIC ACID AND VITAMIN B......Page 333
10.9.2 Pernicious Anemia......Page 334
10.9.3 Neurological Degeneration in Vitamin B Deficiency......Page 335
10.9.4 Folate Deficiency and Neural Tube Defects......Page 336
10.9.5 Folate Deficiency and Cancer Risk......Page 337
10.9.6 Drug-Induced Folate Deficiency......Page 338
10.10 ASSESSMENT OF FOLATE AND VITAMIN B NUTRITIONAL STATUS......Page 339
10.10.1 Plasma and Erythrocyte Concentrations of Folate and Vitamin B......Page 340
10.10.2 The Schilling Test for Vitamin B Absorption......Page 341
10.10.4 Histidine Metabolism–the FIGLU Test......Page 342
10.10.5 The dUMP Suppression Test......Page 343
10.11.2 Vitamin B Requirements......Page 344
10.11.3 Upper Levels of Folate Intake......Page 345
FURTHER READING......Page 347
11.1 METABOLISM OF BIOTIN......Page 350
11.1.1 Bacterial Synthesis of Biotin......Page 353
11.2 THE METABOLIC FUNCTIONS OF BIOTIN......Page 355
11.2.1 The Role of Biotin in Carboxylation Reactions......Page 356
11.2.2 Holocarboxylase Synthetase......Page 358
11.2.3 Biotinidase......Page 360
11.2.4 Enzyme Induction by Biotin......Page 361
11.2.5 Biotin in Regulation of the Cell Cycle......Page 362
11.3 BIOTIN DEFICIENCY......Page 363
11.3.1 Metabolic Consequences of Biotin Deficiency......Page 364
11.4 ASSESSMENT OF BIOTIN NUTRITIONAL STATUS......Page 366
11.6 AVIDIN......Page 367
FURTHER READING......Page 369
12.1 PANTOTHENIC ACID VITAMERS......Page 371
12.2 METABOLISM OF PANTOTHENIC ACID......Page 372
12.2.1 The Formation of CoA from Pantothenic Acid......Page 374
12.2.3 The Formation and Turnover of ACP......Page 376
12.2.4 Biosynthesis of Pantothenic Acid......Page 377
12.3 METABOLIC FUNCTIONS OF PANTOTHENIC ACID......Page 378
12.4.1 Pantothenic Acid Deficiency in Experimental Animals......Page 379
12.4.2 Human Pantothenic Acid Deficiency – The Burning Foot Syndrome......Page 380
12.6 PANTOTHENIC ACID REQUIREMENTS......Page 381
FURTHER READING......Page 382
THIRTEEN Vitamin C (Ascorbic Acid)......Page 383
13.1 VITAMIN C VITAMERS AND NOMENCLATURE......Page 384
13.2 METABOLISM OF VITAMIN C......Page 385
13.2.2 Tissue Uptake of Vitamin C......Page 387
13.2.3 Oxidation and Reduction of Ascorbate......Page 388
13.2.4 Metabolism and Excretion of Ascorbate......Page 389
13.3 METABOLIC FUNCTIONS OF VITAMIN C......Page 390
13.3.1 Dopamine Beta-Hydroxylase......Page 391
13.3.2 Peptidyl Glycine Hydroxylase (Peptide Alpha-Amidase)......Page 392
13.3.3 2-Oxoglutarate–Linked Iron-Containing Hydroxylases......Page 393
13.3.5 The Role of Ascorbate in Iron Absorption and Metabolism......Page 395
13.3.6 Inhibition of Nitrosamine Formation by Ascorbate......Page 396
13.3.7 Pro- and Antioxidant Roles of Ascorbate......Page 397
13.4 VITAMIN C DEFICIENCY – SCURVY......Page 398
13.4.1 Anemia in Scurvy......Page 399
13.5.2 Plasma and Leukocyte Concentrations of Ascorbate......Page 400
13.6.1 The Minimum Requirement for Vitamin C......Page 402
13.6.3 Requirements Estimated from Maintenance of the Body Pool of Ascorbate......Page 404
13.6.4 Higher Recommendations......Page 405
13.6.5 Safety and Upper Levels of Intake of Vitamin C......Page 406
13.7.1 Vitamin C in Cancer Prevention and Therapy......Page 408
13.7.3 Vitamin C and the Common Cold......Page 409
FURTHER READING......Page 410
14.1 CARNITINE......Page 411
14.1.1 Biosynthesis and Metabolism of Carnitine......Page 412
14.1.3 Carnitine as an Ergogenic Aid......Page 414
14.2.1 Biosynthesis and Metabolism of Choline......Page 415
14.2.2 The Possible Essentiality of Choline......Page 417
14.3 CREATINE......Page 418
14.4 INOSITOL......Page 419
14.4.2 The Possible Essentiality of Inositol......Page 420
14.5.1 Biosynthesis of Taurine......Page 422
14.5.2 Metabolic Functions of Taurine......Page 424
14.5.3 The Possible Essentiality of Taurine......Page 425
14.6 UBIQUINONE (COENZYME Q)......Page 426
14.7.1 Allyl Sulfur Compounds......Page 427
14.7.2 Flavonoids and Polyphenols......Page 428
14.7.3 Glucosinolates......Page 429
14.7.4 Phytoestrogens......Page 430
FURTHER READING......Page 432
Bibliography......Page 435
Index......Page 489