Riboflavin

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.