Riboflavin

This volume represents an interdisciplinary approach to an understanding of the chemistry, physiology, and medical significance of the vitamin riboflavin. Information has been reviewed on the physiological role of the vitamin, the metabolic effects of riboflavin deficiency in animals and man, and the regulation of riboflavin metabolism. In each chapter early background material has been included, but the major emphasis has been on the many recent advances that have been made. The early chapters of the book are concerned with the physical and chemical properties of riboflavin and its coenzyme derivatives and the nature of the interactions between flavoprotein apoenzymes and their coenzymes. The various methods currently available for measuring f1avins in biological tissues, particularly in man, have been described in detail, together with newer procedures that appear to have certain advantages over existing techniques. Chapters dealing with the absorption, excretion, and metabolism of riboflavin provide basic data on the processes involved in vitamin uptake and in metabolic transformations.

1 Physical and Chemical Properties of Flavins; Binding of Flavins to Protein and Conformational Effects; Biosynthesis of Riboflavin.- 1. Physical and Chemical Properties of Flavins.- 1.1. Nomenclature and General Properties.- 1.2. Electronic Spectroscopic Properties: Flavoquinones (Flox).- 1.3. Electronic Spectroscopic Properties: Flavohydroquinones (Flred).- 1.4. Reactions of Flavoquinones.- 1.5. Flavin-Metal Interactions.- 2. Effects of Flavin Cofactors on Nonprimary Protein Structure.- 2.1. General Considerations.- 2.2. Specific Flavoproteins.- 2.3. Summary.- 3. Binding of Flavin Cofactors.- 3.1. General Considerations.- 3.2. Covalent Binding.- 3.3. Noncovalent Binding.- 3.4. Summary.- 4. Biosynthesis of Riboflavin.- 4.1. General Considerations.- 4.2. Purines as the Precursor of 6,7-Dimethyl-8-ribityllumazine and Riboflavin.- 4.3. Conversion of 6,7-Dimethyl-8-ribityllumazine to Riboflavin.- 5. References.- 2 Analysis of Riboflavin and Its Derivatives in Biologic Fluids and Tissues.- 1. Introduction.- 2. Chemical Methods.- 2.1. Fluorometric Assay.- 2.2. Enzyme Analysis for Riboflavin Status.- 3. Microbial Methods for Assay of Riboflavin.- 3.1. Tetrahymena pyriformis Method.- 3.2. Lactobacillus casei Method.- 4. Comments and Clinical Applications.- 5. References.- 3 Chromatographic and Radioisotopic Methods for the Analysis of Riboflavin and the Flavin Coenzymes.- 1. Introduction.- 2. The Chromatographic Separation of Flavins.- 2.1. Column Chromatographic Procedures.- 2.2. Paper Chromatography of Flavins.- 2.3. Thin Layer Chromatographic Separation and Purification of Flavins.- 3. Radioisotopic Methods for the Study of 2?14C-Riboflavin Conversion to Flavin Coenzymes by Animal Tissues in Vivo or in Vitro.- 3.1. Extraction, Separation, and Determination of Radioactive Flavins in Animal Tissues.- 3.2. General Remarks about the Method.- 3.3. Application of the Method for in Vivo or in Vitro Studies of Flavin Coenzyme Synthesis.- 4. Competitive Protein Binding Assay of Riboflavin.- 5. References.- 4 Absorption, Protein Binding, and Elimination of Riboflavin.- 1. Absorption.- 1.1. Normal Patterns of Riboflavin Absorption.- 1.2. Factors Affecting Riboflavin Absorption.- 2. Plasma Protein Binding.- 2.1. Human Plasma Protein Binding.- 2.2. Species Differences.- 3. Elimination.- 3.1. Renal Excretion.- 3.2. Biliary Excretion.- 3.3. Minor Routes of Elimination.- 4. General Pharmacology.- 4.1. Summary of Pharmacokinetic Properties.- 4.2. Pharmacologic and Toxic Effects.- 4.3. Clinical Use of Riboflavin.- 5. References.- 5 Metabolism of Riboflavin.- 1. Tissue Uptake, Storage, and Distribution of Flavins and Flavin Coenzymes.- 1.1. Uptake and Storage.- 1.2. Distribution.- 2. Interconversions of Flavins, Flavin Glycosides, and Flavin Coenzymes.- 2.1. Interconversions of Flavins and Flavin Glycosides.- 2.2. Interconversions of Flavins and Flavin Phosphates.- 2.3. Interconversions of Flavin Mononucleotide with Flavin Adenine Dinucleotide.- 3. Excretion and Breakdown of Riboflavin.- 3.1. Turnover and Displacement.- 3.2. Bacterial Degradation.- 4. References.- 6 Nutritional Intake of Riboflavin.- 1. Historical Perspectives.- 2. Farming and Riboflavin Intake.- 3. Processing and Handling of Riboflavin Food Sources.- 3.1. Milk and Milk Products.- 3.2. Meat, Fish, Poultry, Eggs, and Legumes.- 3.3. Fruits and Vegetables.- 3.4. Grain Products.- 4. Intake of Riboflavin.- 5. Recommendations for Improving Nutritional Intake.- 6. References.- 7 Riboflavin Deficiency.- 1. Riboflavin Deficiency in Animals.- 2. Metabolic Effects of Riboflavin Deficiency.- 3. Riboflavin Deficiency in Man.- 3.1. Clinical Aspects of Riboflavin Deficiency.- 3.2. Diagnosis of Riboflavin Deficiency.- 3.3. Prevention and Treatment of Riboflavin Deficiency.- 4. References.- 8 Experimental Dietary and Antagonist-Induced Human Riboflavin Deficiency.- 1. Introduction.- 2. Dietary Induction of Deficiency.- 2.1. Experimental Diets.- 2.2. Clinical Manifestations of Deficiency.- 3. Antagonist-Induced Deficiency.- 3.1. Clinical Pharmacology of Antagonists.- 3.2. Galactoflavin-Induced Riboflavin Deficiency.- 4. Summary.- 5. References.- 9 Riboflavin Deficiency and Congenital Malformations.- 1. Introduction.- 2. Early Nutrition Experiments.- 3. Riboflavin Deficiency as a Teratogenic Method.- 4. Riboflavin Antimetabolites.- 5. Coenzyme and Enzyme Studies in Embryonal Tissues.- 6. Intrepretations.- 7. Summary.- 8. References.- 10 Biological Activities of Analogs of Riboflavin.- 1. General Background Information.- 1.1. Biological Activity in the Rat.- 1.2. Biological Activity for Lactobacillus casei.- 1.3. Scope of Compounds to Be Described.- 2. Derivatives of Riboflavin.- 3. Isomers of Riboflavin.- 3.1. Modifications of Side Chain at Position 10.- 3.2. Modification of Positions of Substituents on Aromatic Ring.- 4. Homologs of Riboflavin.- 4.1. 7-Methyl-flavin (X).- 4.2. 8-Methyl-flavin (XI).- 4.3. 7-Ethyl-flavin (XII).- 4.4. 8-Ethyl-flavin (XIII).- 4.5. 7-Ethyl-8-methyl-flavin (XIV).- 4.6. 7-Methyl-8-ethyl-flavin (XV).- 4.7. 7,8-Diethyl-riboflavin (XVI).- 5. Analogs of Riboflavin.- 5.1. Modifications of the Side Chain at Position 10.- 5.2. Modifications of Substituents at Positions 7 and 8.- 5.3. Modifications of Side Chain at Position 10 and the Substituents at Positions 7 and 8.- 5.4. Miscellaneous Modifications.- 6. Biological Activity of Flavins in Other Systems.- 6.1. Warburg’s “Old Yellow Enzyme”.- 6.2. The Riboflavin-Deficient Egg.- 7. Structure-Activity Relationships.- 8. References.- 11 Riboflavin and Cancer.- 1. Introduction.- 2. Spontaneous and Transplanted Cancers.- 3. Chemical Carcinogenesis.- 4. Drug Metabolism in Cancer.- 5. Effects of Cancer on Tissue Flavin Levels.- 6. Summary and Conclusions.- 7. References.- 12 Hormonal Regulation of Riboflavin Metabolism.- 1. Introduction.- 2. Androgen and Estrogen.- 2.1. Glandular Structure in Riboflavin Deficiency.- 2.2. Estrogenic Effects upon Riboflavin Binding in Plasma.- 3. Insulin and Diabetes.- 3.1. Blood Sugar Levels in Riboflavin Deficiency.- 3.2. Response to Insulin in Riboflavin Deficiency.- 3.3. Glycogen Synthesis.- 3.4. Riboflavin Metabolism in Clinical Diabetes.- 3.5. Hypoglycin Toxicity.- 4. Adrenal Hormones and ACTH.- 4.1. Early Studies on Adrenalectomized Animals.- 4.2. Glandular Structure and Function in Riboflavin Deficiency.- 4.3. ACTH Stimulation of Flavin Synthesis.- 4.4. Clinical Studies of Riboflavin Metabolism.- 5. Thyroid.- 5.1. Early Studies Relating Riboflavin to Growth.- 5.2. Clinical Studies of Riboflavin Metabolism in Hyperthyroidism.- 5.3. Riboflavin Deficiency and Thyroid Function.- 5.4. Flavin-Induced Deiodination of Thyroxine.- 5.5. Stimulation of Flavin Synthesis by Thyroid Hormones.- 5.6. Enzyme Induction in Riboflavin Deficiency.- 5.7. Clinical Studies of Flavoprotein Enzymes in Thyroid Disease.- 5.8. Developmental Effects of Thyroid Hormone.- 6. Summary and Conclusions.- 7. References.