The Year in Metabolism

1 Cyclic GMP in Metabolism: Interrelationships of Biogenic Amines, Hormones, and Other Agents.- 1.1. Introduction.- 1.2. Formation and Degradation of Cyclic GMP.- 1.2.1. Guanylate Cyclases.- 1.2.2. Cyclic Nucleotide Phosphodiesterases and Other Mechanisms of Cyclic Nucleotide Disposal.- 1.2.3. Cyclic Nucleotide Protein Kinases.- 1.3. Regulation of Cyclic GMP in Tissues.- 1.3.1. Effects of Hypophysectomy and Adrenalectomy.- 1.3.2. Effects of Choline Esters.- 1.3.3. Effects of ?-Adrenergic Agonists.- 1.3.4. Effects of Prostaglandins.- 1.3.5. Effects of Calcium.- 1.3.6. Effects of Azide, Hydroxylamine, and Various Nitro Compounds.- 1.3.7. Effects of Other Agents.- 1.4. Some Physiologic Effects That May Correlate with Cyclic GMP.- 1.4.1. Smooth-Muscle Contraction.- 1.4.2. Heart.- 1.4.3. Secretion and Transport.- 1.4.4. Histamine Release.- 1.4.5. Cell Growth and Proliferation.- 1.4.6. Platelet Aggregation.- 1.4.7. Other Processes.- 1.5. Clinical Studies with Cyclic Nucleotides.- 1.5.1. Cyclic Nucleotides in Tissues.- 1.5.1.1. Psoriasis.- 1.5.1.2. Tumors.- 1.5.2. Cyclic Nucleotides in Extracellular Fluids.- 1.5.2.1. Parathyroid Disorders.- 1.5.2.2. Cystic Fibrosis.- 1.5.2.3. Cushing's Disease.- References.- 2 Diabetes Mellitus.- 2.1. Heterogeneity of Diabetes Mellitus.- 2.1.1. Genetic Heterogeneity.- 2.1.1.1. The Histocompatability System (HLA) and Genetic Susceptibility to Diabetes Mellitus.- 2.1.1.2. Inheritance of (Genetic Susceptibility to) Virus-Induced Diabetes Mellitus.- 2.1.1.3. Autoimmunity in Diabetes Mellitus.- 2.1.1.4. Environmental Factors-Viruses and Other Infectious or Chemical Agents.- 2.1.2. Insulin Secretion.- 2.1.2.1. Prognostic Significance of Heterogeneity of Insulin Responses to Glucose in Mild Diabetes.- 2.1.2.2. Mechanism of Insulin Secretion Relevant to Clinical Diabetes Mellitus.- 2.1.2.3. Measurement of Beta-Cell Secretory Products-Connecting Peptide.- 2.1.3. Insulin Resistance.- 2.1.3.1. Evidence for Insulin Resistance.- 2.1.3.2. Mechanism for Insulin Resistance: Decreased Insulin Binding to Insulin Receptors.- 2.2. Relationship of Fuels to Hormonal Release and Fuel Economy.- 2.3. Glucagon Secretion-Somatostatin.- 2.4. Epidemiological Findings.- 2.5. Control of Diabetes.- 2.5.1. General Considerations.- 2.5.2. Glycosylated Hemoglobin and Diabetic Control.- 2.6. Long-Term Complications.- 2.6.1. Diabetic Microangiopathy.- 2.6.1.1. Changes in Plasma Proteins.- 2.6.1.2. Changes in Microvascular Permeability.- 2.6.1.3. Biochemical Studies.- 2.6.1.4. Muscle Capillary Basement Membrane Thickening.- 2.6.1.5. Diabetic Retinopathy.- 2.6.1.6. Diabetic Nephropathy.- 2.6.2. Diabetic Macroangiopathy.- 2.6.2.1. Prevalence.- 2.6.2.2. Pathogenetic Factors.- 2.6.3. Diabetic Neuropathy.- 2.6.3.1. Clinical Aspects.- 2.6.3.2. Pathogenetic Factors.- 2.6.4. Disturbance of Growth and Accelerated Aging in Diabetes Mellitus.- 2.6.5. Prevention and Treatment-Islet and Pancreas Transplantation.- 2.7. Diabetes in Pregnancy.- 2.8. Treatment of Diabetes Mellitus.- 2.8.1. Dietary Treatment.- 2.8.2. Insulin Treatment.- 2.8.2.1. Ketoacidosis.- 2.8.2.2. Chronic Therapy.- 2.8.3. Oral Hypoglycemic Therapy.- 2.8.3.1. Sulfonylureas.- 2.8.3.2. Phenformin.- References.- 3 Glucagon and Somatostatin.- 3.1. Immunoreactive Glucagons in Tissues and Plasma.- 3.1.1. Primary Structure of Glucagon.- 3.1.2. "Glucagonlike Immunoreactivity".- 3.1.3. Glucagon Biosynthesis.- 3.1.4. Tissue Immunoreactive Glucagon.- 3.1.5. Plasma Immunoreactive Glucagon.- 3.2. Structure-Function Relationships of Glucagon.- 3.2.1. Biological.- 3.2.2. Immunologic.- 3.3. Molecular Basis for Glucagon Actions.- 3.4. Glucagon Metabolism, Clearance, and Degradation.- 3.5. Physiologic Actions of Glucagon.- 3.5.1. Hepatic Glycogenolysis.- 3.5.2. Gluconeogenesis.- 3.5.2.1. Molecular.- 3.5.2.2. Physiologic.- 3.5.3. Ketogenesis.- 3.6. Physiologic Roles of Glucagon in Fuel Homeostasis.- 3.6.1. Maintenance of Basal Hepatic Glucose Production.- 3.6.2. Increase in Hepatic Glucose Production during Protein Meals.- 3.6.3. Increase in Hepatic Glucose Production during Exercise.- 3.6.4. Effects of Glucagon on Lipids and Ketones.- 3.7. Concept of the Bihormonal Unit.- 3.8. Control of Glucagon Secretion.- 3.8.1. Glucose.- 3.8.2. Amino Acids.- 3.8.3. Free Fatty Acids.- 3.8.4. Calcium.- 3.8.5. Cyclic 3?,5?-Adenosine Monophosphate.- 3.8.6. Adrenergic Stimulation-Stress and Exercise.- 3.8.7. Hormones.- 3.8.7.1. Gastrointestinal Hormones.- 3.8.7.2. Growth Hormone.- 3.8.7.3. Neurotensin and Substance P.- 3.8.7.4. Glucocorticoids.- 3.8.7.5. Prostaglandins.- 3.9. Extrapancreatic Glucagon.- 3.10. Somatostatin.- 3.10.1. Pancreatic Somatostatin.- 3.10.1.1. Paracrine Actions of Somatostatin.- 3.10.1.2. Endocrine Actions of Somatostatin.- 3.10.1.3. Mechanism of Action on Islet Cells.- 3.11. Morphofunctional Interrelationships of the Endocrine Pancreas: Microanatomic Organization of the Islets of Langerhans.- 3.11.1. Organization of Islet Cells.- 3.11.2. Subcellular Specialization of Islet Cells.- 3.12. Importance of Glucagon in Clinical Medicine-Diabetes Mellitus.- 3.12.1. A-Cell Function in Human Diabetes.- 3.12.2. The Bihormonal Abnormality Hypothesis.- 3.12.3. Glucagon Suppression as a Therapeutic Adjunct in Juvenile Diabetes.- 3.12.4. Glucagonoma.- References.- 4 Body Fuel Metabolism.- 4.1. Introduction.- 4.2. Glucose Metabolism.- 4.2.1. Glucose Absorption: Effects of Somatostatin.- 4.2.2. Glucose Production.- 4.2.2.1. Protein Ingestion.- 4.2.2.2. Starvation.- 4.2.2.3. Evanescent Effects of Hyperglucagonemia.- 4.2.2.4. Evanescent Effects of Hypoglucagonemia: Prolonged Infusion of Somatostatin.- 4.2.3. Insulin and Hepatic Glucose Output.- 4.2.4. Counterregulation during Insulin Hypoglycemia.- 4.2.5. Neonatal Hypoglycemia.- 4.3. Amino Acid Metabolism.- 4.3.1. Alanine Synthesis in Muscle.- 4.3.2. Metabolism of Branched-Chain Amino Acids in Normal and Diabetic Subjects.- 4.4. Ketone and Fatty Acid Metabolism.- 4.4.1. Hormonal Regulation of Ketogenesis.- 4.4.2. Substrate Regulation of Ketogenesis.- 4.4.3. Role of Ketone Disposal in Hyperketonemia.- 4.5. Fuel Metabolism in Exercise.- 4.5.1. Influence of Glucose Ingestion.- 4.5.2. Glucose-Sparing Effect of Free Fatty Acids.- 4.5.3. Interaction of Exercise and Insulin in Diabetes.- References.- 5 What's New in the Treatment of Obesity?.- 5.1. Introduction.- 5.2. The Core Problem of Treatment.- 5.3. Hypothetical Defended Variables in Obesity.- 5.3.1. Hyperphagia.- 5.3.2. Symbolic Meaning of Obesity.- 5.3.3. A Life Style.- 5.3.4. Adipose Mass.- 5.4. Implications for Treatment.- 5.5. Current New Approaches in Treatment.- 5.5.1. The Protein-Sparing Modified Fast.- 5.5.2. Behavior Modification.- 5.5.3. Jejunoileal Shunt.- 5.6. Conclusion.- References.- 6 Disorders of Lipid and Lipoprotein Metabolism.- 6.1. Introduction.- 6.2. Lipoprotein Structure and Metabolism.- 6.2.1. General Review.- 6.2.2. The Lp(a) Lipoprotein.- 6.2.3. Lipoprotein-X and Liver Disease.- 6.3. Hyperlipidemias.- 6.3.1. Definition and Classification.- 6.3.2. Epidemiology.- 6.4. High-Density-Lipoprotein Levels and Coronary Heart Disease.- 6.4.1. Epidemiologic Studies.- 6.4.2. Familial Hyperalpha and Familial Hypobeta Lipoproteinemia.- 6.4.3. Possible Mechanisms.- 6.4.4. Implications.- 6.5. Type III Hyperlipoproteinemia.- 6.6. Cholesterol Metabolism and Its Regulation.- 6.6.1. In Intact Humans.- 6.6.2. In Cultured Cells.- 6.7. Familial Hypercholesterolemia.- 6.7.1. Genetics.- 6.7.2. Pathogenesis.- 6.7.3. Therapy.- 6.8. ?-Sitosterolemia and Cerebrotendinous Xanthomatosis.- 6.9. Hypertriglyceridemia.- 6.9.1. Pathophysiology and Other Features.- 6.9.2. Hypertriglyceridemia and Coronary Heart Disease.- 6.10. Chronic Renal Failure and Hyperlipidemia.- 6.11. Treatment of Hyperlipidemia.- 6.11.1. Diet.- 6.11.2. Drugs.- 6.11.3. Partial Ileal Bypass Surgery.- 6.11.4. Primary Prevention of Ischemic Heart Disease.- References.- 7 Metabolism of Amino Acids and Organic Acids.- 7.1. Introduction.- 7.2. Phenylketonuria and Its Variants.- 7.2.1. Phenylalanine Hydroxylation: Enzymes and Coenzymes.- 7.2.1.1. The Hydroxylation System.- 7.2.1.2. The Defect in Classic Phenylketonuria.- 7.2.1.3. "Benign" Hyperphenylalaninemia.- 7.2.1.4. Dihydropteridine Reductase Deficiency.- 7.2.2. Clinical Phenylketonuria: Incidence and Outcome.- 7.2.2.1 Phenylketonuria as a Balanced Polymorphism.- 7.2.2.2 Dietary Treatment of Phenylketonuria.- 7.2.2.3 Maternal Phenylketonuria.- 7.3. The ?-Glutamyl Cycle and 5-Oxoprolinuria.- 7.3.1. 5-Oxoprolinuria.- 7.3.2. The ?-Glutamyl Cycle.- 7.3.3. Biochemical Basis of 5-Oxoprolinuria.- 7.3.4. Evidence For and Against the Role of the y-Glutamyl Cycle in Amino Acid Transport.- 7.4. Jamaican Vomiting Sickness and Glutaric Aciduria Type II: Similar Organic Acidurias with Different Etiologies.- 7.4.1. Jamaican Vomiting Sickness.- 7.4.1.1. Metabolic Effects of Hypoglycin.- 7.4.1.2. Inhibition of Acyl-CoA Dehydrogenases by Methylenecyclopropylacetic Acid.- 7.4.1.3. Recent Studies on Jamaican Vomiting Sickness.- 7.4.2. Glutaric Aciduria Type II.- References.- 8 Disorders of Purine and Pyrimidine Metabolism.- 8.1. Introduction.- 8.2. Purine Metabolism.- 8.2.1. Role of Liver in Processing Purines of the Bloodstream.- 8.2.2. Purines as a Source of Ammonia Production.- 8.2.3. Regulation of Purine Synthesis.- 8.2.4. Effects of Purine Compounds on the Immune System.- 8.2.5. Changes in Adenosine Metabolism with Mitogenic Stimulation.- 8.2.6. Possible Role of Cyclic AMP in Immunosuppression.- 8.2.7. Role of Adenosine Deaminase in Metabolism or Action of Drugs.- 8.3. Adenosine Deaminase (ADA) Deficiency Associated with Severe Combined Immunodeficiency Disease.- 8.3.1. Frequency.- 8.3.2. Metabolic Studies of ADA-Deficient Patients.- 8.3.3. New Approach to Treatment of ADA Deficiency.- 8.3.4. Metabolic Consequences of ADA Deficiency.- 8.3.5. Tissue Distribution of ADA.- 8.3.6. Tissue Forms of ADA.- 8.3.7. Genetic Heterogeneity of Residual ADA Activity.- 8.3.8. Possible Pathogenetic Mechanism of ADA Deficiency.- 8.4. Increased Activity of ADA in Red Cells Associated with Hereditary Hemolytic Anemia.- 8.5. Purine Nucleoside Phosphorylase (PNP) Deficiency.- 8.5.1. Clinical Presentation.- 8.5.2. Metabolites in Urine.- 8.5.3. Metabolites in Blood and Serum.- 8.5.4. PNP Enzyme Activity and Metabolism of Erythrocytes and Fibroblasts.- 8.5.5. Purine Production in Cultured Fibroblasts.- 8.5.6. Possible Pathogenetic Mechanisms of PNP Deficiency.- 8.5.7. Properties of Purified PNP.- 8.6. Purine 5?-Nucleotidase Deficiency in Primary Hypogammaglobulinemia.- 8.6.1. Clinical Presentation.- 8.7. Hereditary Xanthinuria.- 8.8. Hypoxanthine-Guanine Phosphoribosyl transferase (HPRT) Deficiency.- 8.8.1. Clinical Correlations with HPRT Activity.- 8.8.2. Biochemical Mechanism of the Neurological Defect.- 8.8.3. Nature of the Enzyme Abnormality.- 8.8.4. Mechanism of Purine Overproduction.- 8.8.5. Genetics of HPRT Deficiency.- 8.8.6. Other Conditions Associated with HPRT Deficiency.- 8.9. Increased Activity of Phosphoribosylpyrophosphate Synthetase.- 8.9.1. Inheritance.- 8.10. Adenine Phosphoribosyltransferase (APRT) Deficiency.- 8.10.1. Clinical Presentation.- 8.10.2. Chemical Composition of Calculi.- 8.10.3. Therapy.- 8.10.4. APRT Activity in Erythrocytes.- 8.10.5. Adenine and Other Purine Metabolites in Urine.- 8.10.6. Genetics.- 8.10.7. APRT Deficiency in Cell Culture.- 8.11. Nucleoside Triphosphate Pyrophosphohydrolase Deficiency.- 8.12. Gouty Arthritis.- 8.12.1. Metabolic Abnormalities Associated with Gout.- 8.12.2. Clinical Features of Gouty Arthritis.- 8.12.3. Local Conditions That Favor Urate Deposition.- 8.12.4. Characteristics of the Monosodium Urate Crystal.- 8.12.5. Uric Acid and the Kidney.- 8.12.6. Treatment of Gout.- 8.13. Abnormalities of Pyrimidine Metabolism.- 8.13.1. Pyrimidine 5?-Nucleotidase Deficiency.- 8.13.2. Hyperammonemia with Orotic Aciduria.- 8.13.3. Drug and Nutritional Factors That Affect Pyrimidine Metabolism.- 8.13.4. Orotic Aciduria Accompanying Other Errors of Metabolism.- 8.14. Chemotherapy of Malignancies and Viral Diseases.- References.- 9 Divalent Ion Metabolism.- 9.1. Regulation of Calcium Homeostasis.- 9.1.1. Parathyroid Hormone.- 9.1.1.1. Divalent Ion Control of Parathyroid Hormone Secretion.- 9.1.1.2. Actions of Parathyroid Hormone on Bone.- 9.1.1.3. Actions of Parathyroid Hormone on the Kidney.- 9.1.1.4. Immunoassay for Parathyroid Hormone.- 9.1.2. Vitamin D.- 9.1.2.1. Chemistry and Metabolism of Vitamin D.- 9.1.2.2. Actions of Vitamin D.- 9.1.2.3. Plasma Transport of Vitamin D.- 9.1.2.4. Assays for 25(OH)D, 1,25(OH)2D, and Other Vitamin D Sterols.- 9.1.2.5. Vitamin D Toxicity.- 9.1.2.6. Absence of Vitamin D Action.- 9.1.3. Other Factors That Affect Calcium Homeostasis 355 9.1.3.1. Calcium-Handling by the Kidney.- 9.2. Phosphate Metabolism.- 9.2.1. Regulation by the Kidney.- 9.2.1.1. Effects of Dietary Intake of Phosphorus.- 9.2.1.2. Effects of Parathyroid Hormone.- 9.2.1.3. Effects of Serum Calcium Level.- 9.2.1.4. Actions of Vitamin D.- 9.2.1.5. Other Factors That Affect Renal Phosphate-Handling.- 9.2.2. Phosphate Depletion.- 9.3. Magnesium Metabolism.- 9.3.1. The Kidney in Magnesium Homeostasis.- 9.3.2. Magnesium Depletion.- References.- 10 Nutrition, Growth, and Development.- 10.1. Introduction.- 10.2. Malnutrition and the Mechanisms of Cellular Growth.- 10.3. Genetic Obesity.- 10.3.1. Changes in Adipose Tissue during Normal Growth.- 10.3.2. Animal Models of Genetic Obesity.- 10.3.3. Human Studies.- 10.4. Nutrition and Pregnancy.- References.- 11 Metabolic Aspects of Renal Stone Disease.- 11.1. Introduction.- 11.2. Incidence of Renal Stone Disease.- 11.3. Classification of Renal Stone Disease.- 11.4. Renal Stone Disease Secondary to Increased Crystalloid Excretion.- 11.4.1. Hypercalciuria.- 11.4.2. Hyperoxaluria.- 11.4.3. Hyperuricosuria.- 11.4.4. Cystine and Xanthine Stones.- 11.5. Renal Stone Disease Secondary to Physicochemical Changes in Urine Composition.- 11.6. Idiopathic Renal Stone Disease.- 11.7. Treatment of Renal Stone Disease.- References.- 12 Metabolism and Metabolic Actions of Ethanol.- 12.1. Metabolism of Ethanol.- 12.1.1. Role of Alcohol Dehydrogenase and Interaction of Dietary Factors with Ethanol and Acetaldehyde Metabolism.- 12.1.2. Role, Nature, and Metabolic Consequences of Non-ADH Pathways for Ethanol Oxidation.- 12.1.3. Effects of Chronic Ethanol Consumption on Ethanol Metabolism.- 12.1.4. Influence of Liver Disease, Ethnic Background, Circadian Rhythm, and Other Factors on Ethanol Metabolism.- 12.2. Interaction of Ethanol with Androgen Metabolism.- 12.3. Interaction of Ethanol with Amino Acid Metabolism.- 12.4. Effects of Ethanol on the Gastrointestinal Tract.- 12.4.1. Metabolic Consequences of Gastric Alterations Induced by Alcohol.- 12.4.2. Metabolic Consequences of Intestinal Changes Produced by Alcohol.- References.