The Year in Metabolism 1977

ISBN-13: 9781468425017 / Angielski / Miękka / 2012 / 448 str.

Norbert Freinkel

Opis

In the words of Disraeli, "To be conscious that you are ignorant of the facts is a great step to knowledge. " For most of us, the conscious awareness of relative ignorance is an uncomfortable aspect of daily life. New data appear in such inexorable profusion that the necessity for continuous retooling has joined death and taxes as an inescapable component of our destinies. Perhaps it is this "consciousness of ignorance" that accounts for the success of the preceding volumes of this new series. The Year in Metabolism and The Year in Endocrinology series were introduced with the avowed intention of "providing an efficient and enjoyable bridge between those who are creating new knowledge at the bedside and the professional consciousness of those for whom such knowledge is ultimately intended. " That objective seems particularly appropriate at a time when the award of the 1977 Nobel Prize in Medicine or Physiology to Guillemin, Schally, and Yalow has served to emphasize the epoch-making advances that have characterized the recent course of endocrinology and me bolism. For the 1977 volume of The Year in Metabolism, the previous formula has been preserved. The same internationally recognized authorities again have contributed commentaries about the progress in their areas of expertise. They have been joined by Drs. Jack W. Coburn, David L. Hartenbower, and Charles R. Kleeman, who have provided a new section on Divalent Ion Metabolism.

Spis treści

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.