The Fat-Soluble Vitamins

The first demonstration of the existence of a vitamin and the full recognition of this fact are often attributed to the work of McCollum, who found that a sub­ stance in butterfat and cod-liver oil was necessary for growth and health of ani­ mals fed purified diets. It became obvious that an organic substance present in microconcentrations was vital to growth and reproduction of animals. Following the coining of the word vitamine by Funk, McCollum named this fat-soluble sub­ stance vitamin A. We can, therefore, state that vitamin A was certainly one of the first known vitamins, yet its function and the function of the other fat-soluble vitamins had remained largely unknown until recent years. However, there has been an explosion of investigation and new information in this field, which had remained quiescent for at least two or three decades. It is now obvious that the fat-soluble vitamins function quite differently from their water-soluble counter­ parts. We have learned that vitamin D functions by virtue of its being converted in the kidney to a hormone that functions to regulate calcium and phosphorus metabolism. This new endocrine system is in the process of being elucidated in detail, and in addition, the medical use of these hormonal forms of vitamin D in the treatment of a variety of metabolic bone diseases has excited the medical com­ munity.

Contenu

1 Vitamin A.- 1.1. Historical Developments in Vitamin A Research.- 1.2. Nomenclature and Chemistry.- 1.3. Biogenesis of Carotenoids.- 1.3.1. Squalene-Condensing System.- 1.3.2. Carotenoid-Condensing Pathway.- 1.3.3. Stereochemistry of the Carotenoid Pathway.- 1.4. Conversion of ß-Carotene to Retinol.- 1.5. Retinoic Acid.- 1.5.1. Urinary Metabolites of Retinoic Acid.- 1.5.2. Tissue Metabolism of Retinoic Acid.- 1.6. The Visual Function.- 1.7. Isomers of Retinal.- 1.8. Bacteriorhodopsin of Halobacterium halobium.- 1.9. The Reproductive Function.- 1.10. Vitamin A and Bone.- 1.11. Introduction to the Epithelial Function.- 1.11.1. Excess Vitamin A.- 1.11.2. Vitamin A and Macromolecular Synthesis in Epithelial Tissues: Morphological Observations.- 1.12. Retinyl Glycosides.- 1.13. Retinol-Binding Proteins.- 1.13.1. Regulation of RBP Metabolism by the Vitamin A Status in the Rat.- 1.13.2. Localization of Retinol and RBP in Rat Liver.- 1.14. Binding Proteins in Tissues Other Than Blood.- 1.15. Vitamin A and Transformation.- 1.16. Conclusion.- 1.17. References.- 2 Vitamin D.- 2.1. Introduction.- 2.2. Historical.- 2.2.1. Discovery of Vitamin D.- 2.2.2. Physiology of Vitamin D Action.- 2.2.3. Vitamin D Metabolism.- 2.3. Absorption of Vitamin D.- 2.4. Production of Vitamin D in the Skin.- 2.5. Occurrence of Vitamin D Naturally.- 2.6. Structure and Physical Constants of the D Vitamins and Their Precursors.- 2.7. Vitamin D Deficiency.- 2.7.1. Rickets and Osteomalacia.- 2.7.2. Hypocalcemic Tetany as a Disease of Vitamin D Deficiency..- 2.7.3. Physiological Functions of Vitamin D in the Prevention of the Deficiency Diseases.- 2.8. Vitamin D Metabolism.- 2.9. Regulation of Vitamin D Metabolism: Definition of the Vitamin D Endocrine System.- 2.10. Regulation of the Vitamin D System by the Need for Phosphorus..- 2.11. Regulation of Vitamin D Metabolism by the Sex Hormones and by Other Endocrine Systems.- 2.12. Mechanism of Action of l,25-(OH)2D3.- 2.12.1. Intestinal Calcium Absorption.- 2.12.2. Mobilization of Calcium from Bone.- 2.12.3. Mechanism Whereby 1,25-(OH)2D3 Stimulates Intestinal Phosphate Transport.- 2.13. Analogues of l,25-(OH)2D3.- 2.14. Toxicity of Vitamin D.- 2.15. Vitamin D Metabolism and Disease.- 2.15.1. Hypoparathyroidism and Pseudohypoparathyroidism.- 2.15.2. Renal Osteodystrophy.- 2.15.3. Corticoid-Induced Osteoporosis.- 2.15.4. Postmenopausal and Senile Osteoporosis.- 2.15.5. Hepatic Disorders.- 2.15.6. Osteomalacia Induced by Phenobarbital and Dilantin.- 2.15.7. Neonatal Hypocalcemia.- 2.15.8. Vitamin D Dependency Rickets.- 2.15.9. Vitamin D Resistant Hypophosphatemic Rickets.- 2.16. Conclusion.- 2.17. References.- 3 Vitamin E.- 3.1. Introduction.- 3.2. History.- 3.2.1. Discovery of Vitamin E.- 3.2.2. A Variety of Vitamin E Deficiency Diseases in Different Species.- 3.2.3. Characterization, Identification, and Synthesis of Vitamin E..- 3.2.4. Vitamin E Interrelationships with Other Factors.- 3.2.5. Research That Brought Some Order Out of the Confusion.- 3.3. Chemistry of Vitamin E.- 3.3.1. Chemical Synthesis of dl-?-Tocopherol.- 3.3.2. Metabolic Degradation Products of Tocopherol.- 3.3.3. Nomenclature.- 3.3.4. Properties of the Vitamins E.- 3.3.5. Properties of Derivatives.- 3.4. Deficiency Diseases.- 3.4.1. Deficiency Diseases in Mammals.- 3.4.2. Anemia in Monkeys and Pigs.- 3.4.3. Vitamin E Deficiency Diseases of Poultry.- 3.4.4. Vitamin E Deficiency in Man.- 3.4.5. Diseases Responsive to Vitamin E Therapy.- 3.5. Metabolic Roles of Vitamin E.- 3.5.1. Action of Vitamin E Complementary to the Action of the Selenoenzyme Glutathione Peroxidase.- 3.5.2. Vitamin E and Xanthine Oxidase.- 3.5.3. Interrelationships with Other Factors.- 3.6. Vitamin E Requirements.- 3.7. Sources of Vitamin E.- 3.8. Methods of Assay.- 3.8.1. Biological Assays.- 3.8.2. Chemical Assays.- 3.9. Absorption, Transport, and Storage of Vitamin E.- 3.9.1. Essential Role of Lipid-Bile Salt Micelles for Intestinal Absorption of Tocopherol.- 3.9.2. Studies on Absorption and Retention of d- and l-Epimers of ?-Tocopherol.- 3.9.3. Storage.- 3.10. High Dietary Intakes of Vitamin E.- 3.11. Conclusions.- 3.12. References.- 4 Vitamin K.- 4.1. Introduction.- 4.1.1. Historical Background.- 4.1.2. Available Review Articles.- 4.1.3. Nomenclature.- 4.1.4. Isolation and Chemical Characterization.- 4.1.5. Blood Coagulation.- 4.2. Biological Activity and Physiology.- 4.2.1. Structure-Activity Correlations.- 4.2.2. Intestinal Absorption.- 4.2.3. Tissue Uptake and Distribution.- 4.2.4. Form of Vitamin K in Tissues.- 4.2.5. Cellular Distribution.- 4.3. Metabolism.- 4.3.1. Biosynthesis.- 4.3.2. Metabolic Degradation.- 4.3.3. Vitamin K Epoxide.- 4.4. Dietary Requirement.- 4.4.1. Requirement for Animals.- 4.4.2. Human Requirement.- 4.5. Antagonists of Vitamin Action.- 4.5.1. Coumarin Derivatives.- 4.5.2. 1,3-Indandiones.- 4.5.3. 2-Halo-3-phytyl-l,4-naphthoquinones.- 4.5.4. Other Antagonists.- 4.6. Metabolic Role of Vitamin K.- 4.6.1. Historical Development.- 4.6.2. Indirect Evidence for a Prothrombin Precursor Protein.- 4.6.3. Immunochemical Evidence for a Prothrombin Precursor.- 4.6.4. Isolation and Characterization of the Abnormal Prothrombin.- 4.6.5. Characterization of ?-Carboxyglutamic Acid.- 4.6.6. Metabolism of ?-Carboxyglutamic Acid.- 4.6.7. Isolation of Liver Prothrombin Precursor Proteins.- 4.6.8. Prothrombin Production-Vitamin K Dependent Carboxylation.- 4.6.9. Molecular Role of Vitamin K.- 4.6.10. Vitamin K Epoxidase and Epoxide Reductase.- 4.6.11. Mechanism of Coumarin Action.- 4.7. Non-Clotting-Factor Role of Vitamin K.- 4.7.1. Vitamin K and Electron Transport.- 4.7.2. Other Vitamin K Dependent Plasma Proteins.- 4.7.3. Nonplasma Vitamin K Dependent Proteins.- 4.7.4. Other Effects of Vitamin K Deficiency or Coumarin Treatment.- 4.8. Conclusion.- 4.9. References.