Contemporary Metabolism

Volume 1
Springer (Verlag)
  • erschienen am 6. Dezember 2012
  • |
  • XXVI, 498 Seiten
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978-1-4684-3447-7 (ISBN)
Despite a new title, Contemporary Metabolism, Volume 1 is actually the third volume in a continuing series and succeeds The Year in Metabolism 1975- 1976 and The Year in Metabolism 1977. As in the earlier volumes, the same internationally recognized authorities review the noteworthy recent devel opments in their areas of expertise. In many instances they also address aspects that have not been considered previously. In this volume, Dr. J. Edwin Seegmiller again updates progress in understanding disorders of purine and pyrimidine metabolism. However, particular emphasis is placed on the emerging relationships with immune mechanisms. Dr. Charles S. Lieber is joined by Dr. Enrique Baraona in a continuing review of metabolic actions of ethanol. This chapter examines effects of ethanol on protein metabolism and selected features of lipid metabolism-two areas that were not included in the earlier volumes. Dr. DeWitt S. Goodman's review of disorders oflipid and lipoprotein metabo lism builds on his previous chapters, but much additional attention is directed to a critical analysis of recent advances in epidemiology and lipoprotein structures. In collaboration with Dr. Brian L. G. Morgan, Dr. Myron Winick devotes his entire chapter to a detailed review of the impact of nutrition upon brain development-an overview that has now been rendered possible by the burgeoning recent developments in this area.
  • Englisch
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  • USA
Springer US
978-1-4684-3447-7 (9781468434477)
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1 Disorders of Purine and Pyrimidine Metabolism.- 1.1. Introduction.- 1.2. Purine Metabolism.- 1.2.1. Hypoxanthine Reutilization as a Normal Regulator of Purine Synthesis de Novo.- 1.2.2. Drugs That Increase Purine Synthesis de Novo.- 1.2.3. Changes in Purine Metabolism with Cellular Proliferation.- 1.2.4. Role of the Purine Nucleotide Cycle.- 1.2.5. Role of the Purine Nucleotide Cycle in Transport Processes.- 1.2.6. Effect of Fructose.- 1.3. Adenosine Deaminase Deficiency Associated with Severe Combined Immunodeficiency Disease.- 1.3.1. Clinical Presentation.- 1.3.2. Frequency.- 1.3.3. Enzyme Abnormality.- 1.3.4. Screening Tests.- 1.3.5. Prenatal Diagnosis.- 1.3.6. Genetic Heterogeneity.- 1.3.7. Metabolic Studies.- 1.3.8. Model Systems of Adenosine Deaminase Deficiency.- 1.3.9. Treatment.- 1.4. Purine Nucleoside Phosphorylase Deficiency.- 1.4.1. Clinical Presentation.- 1.4.2. Enzyme Abnormalities.- 1.4.3. Purine Metabolites in Urine.- 1.4.4. Metabolic Studies.- 1.4.5. Treatment.- 1.4.6. Purine Nucleoside Phosphorylase Distribution in Human Tissues.- 1.5. Biochemical Basis of the Immunodeficiency in Adenosine Deaminase and Purkie Nucleoside Phosphorylase Deficiency.- 1.5.1. Ribonucleoside Accumulation.- 1.5.2. Pyrimidine Starvation.- 1.5.3. Possible Role of Cyclic AMP.- 1.5.4. Deoxyribonucleoside Accumulation.- 1.5.5. Implications for Therapy.- 1.6. Purine 5'-Nucleotidase Deficiency in Hypogammaglobulinemia.- 1.6.1. Clinical Categories with Low Purine 5'-Nucleotidase.- 1.6.2. Enzyme Characteristics.- 1.7. Adenine Phosphoribosyltransferase Deficiency.- 1.7.1. Clinical Presentation.- 1.7.2. Composition of Calculi.- 1.7.3. Purine Metabolites in the Urine and Plasma.- 1.7.4. Adenine Phosphoribosyltransferase Activity in Erythrocytes.- 1.7.5. Treatment.- 1.7.6. Metabolic Significance.- 1.7.7. Frequency.- 1.8. Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency.- 1.8.1. Genetic Heterogeneity.- 1.8.2. Enzyme Characteristics.- 1.8.3. Enzyme Assays.- 1.8.4. Genetic Transformation.- 1.8.5. Neurological Disorders.- 1.8.6. Attempts to Produce a Hypoxanthine-Guanine- Phosphoribosyltransferase-Deficient Mouse.- 1.8.7. Mechanism of Excessive Purine Synthesis.- 1.8.8. Other Metabolic Correlations.- 1.9. Increased Phosphoribosyl-1-Pyrophosphate Synthetase Activity.- 1.9.1. Enzyme Characteristics.- 1.9.2. Inheritance.- 1.9.3. Biochemical Studies.- 1.10. Xanthinuria.- 1.10.1. Conditions Associated with Hypouricemia.- 1.10.2. Clinical Presentation.- 1.11. Gouty Arthritis.- 1.11.1. Hyperuricemia.- 1.11.2. Diagnosis.- 1.11.3. Disorders Associated with Gout.- 1.11.4. The Kidney and Gout.- 1.11.5. Association of Hyperuricemia and Vascular Disease.- 1.11.6. Association of Hyperuricemia with Avascular Necrosis of the Femoral Head.- 1.11.7. Acute Attack of Gout.- 1.11.8. Treatment.- 1.11.9. Metabolic Factors That Contribute to Hyperuricemia.- 1.12. Decreased Adenylate Deaminase Activity.- 1.13. Abnormalities of Pyrimidine Metabolism.- 1.13.1. Ammonia and Pyrimidine Nucleotide Synthesis.- 1.13.2. Pyrimidine 5'-Nucleotidase Deficiency.- 1.13.3. Orotic Aciduria.- 1.14. Abnormalities of DNA Repair (Xeroderma Pigmentosum).- 1.15. Purine and Pyrimidine Compounds as Inhibitors of Viral and Cellular Proliferation.- 1.15.1. Effective Clinical Treatment of Herpes Encephalitis with Adenine Arabinoside.- 1.15.2. New Antiviral Agents.- References.- 2 Metabolic Actions of Ethanol.- 2.1. Effects of Ethanol on Protein Metabolism.- 2.1.1. Origin of the Increased Liver Protein.- 2.1.2. Type of Proteins That Accumulate after Chronic Alcohol Consumption.- 2.1.3. Mechanisms of the Alcohol-Induced Accumulation of Liver Protein.- Effects of Ethanol on Protein Synthesis.- Effects of Ethanol on Protein Secretion.- Effects of Ethanol on Protein Catabolism.- 2.1.4. Summary of the Alcohol-Induced Alterations of Hepatic Protein Metabolism and Possible Consequences.- 2.2. Effects of Ethanol on Lipid Metabolism.- 2.2.1. Liver Upids.- 2.2.2. Alcohol-Induced Alterations in the Metabolism of Serum Lipoproteins.- 2.2.3. Alcohol, Coronary Heart Disease, and High-Density Lipoproteins.- 2.2.4. Conclusion.- References.- 3 Disorders of Lipid and Lipoprotein Metaboiism.- 3.1. Introduction.- 3.2. Lipoprotein Structure and Metabolism.- 3.2.1. General Review.- 3.2.2. Apolipoprotein C-II.- 3.2.3. High-Density Lipoproteins.- 3.2.4. The Lp(a) Lipoprotein.- 3.2.5. Lipoprotein-X and Liver Disease.- 3.3. Type III Hyperlipoproteinemia.- 3.3.1. Diagnosis.- 3.3.2. Apolipoprotein E.- 3.3.3. Pathophysiology; Treatment.- 3.4. Tangier Disease.- 3.5. High-Density Lipoprotein Levels and Coronary Heart Disease.- 3.5.1. Epidemiologic Studies.- 3.5.2. Alcohol, High-Density Lipoproteins, and Coronary Risk.- 3.5.3. Other Clinical Studies.- 3.5.4. Pathophysiology.- 3.5.5. Implications.- 3.6. Cholesterol Metabolism and Its Regulation.- 3.6.1. In Intact Humans.- 3.6.2. In Cultured Cells.- 3.7. Familial Hypercholesterolemia.- 3.7.1. Epidemiologic and Clinical Studies.- 3.7.2. Pathophysiology.- 3.7.3. Therapy.- 3.8. Chronic Renal Failure and Hyperlipidemia.- 3.8.1. Pathophysiology.- 3.8.2. Therapy.- 3.9. Hypertriglyceridemia.- 3.9.1. Pathophysiology.- 3.9.2. Diabetes Mellitus; Other Clinical Studies.- 3.9.3. Treatment Effects: Diet, Drugs, Exercise.- 3.10. Hyperlipidemia and Its Treatment.- 3.10.1. Epidemiologic Studies.- 3.10.2. Definition and Classification.- 3.10.3. Diet.- 3.10.4. Drugs.- 3.10.5. Prevention of Ischemic Heart Disease.- References.- 4 Nutrition and Cellular Growth of the Brain.- 4.1. Methods for Producing Early Malnutrition.- 4.2. Malnutrition and Brain Size.- 4.3. Malnutrition and Cellular Growth of the Brain.- 4.4. Malnutrition and Myelination.- 4.5. Other Effects of Malnutrition on the Growing Brain.- 4.6. Regional Changes Induced by Malnutrition.- 4.7. Malnutrition and Cellular Growth of the Peripheral Nerves.- 4.8. Malnutrition and Cellular Growth of the Human Brain.- References.- 5 Metabolic Aspects of Renal Stone Disease.- 5.1. Introduction.- 5.2. Renal Stone Disease Secondary to Increased Crystalloid Excretion.- 5.2.1. Hypercalciuria.- 5.2.2. Hyperuricosuria.- 5.2.3. Hyperoxaluria.- 5.3. Treatment of Renal Stone Disease.- References.- 6 Hormone Receptors, Cyclic Nucleotides, and Control of Cell Function.- 6.1. Introduction.- 6.2. Receptor Systems.- 6.2.1. Physiological Regulation of Receptors.- 6.2.2. Relationship of Receptors to Adenylate Cyclase.- 6.2.3. Opiate Receptors and Endorphins.- 6.2.4. Catecholamine Receptors.- Adrenergic Receptors.- a-Adrenergic Receptors.- Dopamine.- 6.2.5. Hormone Receptors in the Kidney.- 6.2.6. Somatomedin Receptors, Multiplication- Stimulating Activity, and Other Growth Factors.- 6.2.7. Insulin Receptors.- 6.3. Regulation of Adenylate Cyclase.- 6.3.1. Guanine Nucleotide Control.- 6.3.2. Guanosine Triphosphatase.- 6.3.3. Guanine Nucleotides and Agonist Affinity.- 6.3.4. Cholera Toxin and Adenylate Cyclase.- 6.4. Protein Kinases.- 6.4.1. Cell Regulation by Occupied Cyclic AMP Receptors.- 6.5. Calcium Regulation of Cyclic Nucleotide Concentration.- 6.6. Cyclic Nucleotides in the Extracellular Fluids.- 6.6.1. Nephrogenous Cyclic AMP in Parathyroid and Related Disorders.- References.- 7 Diabetes Mellitus.- 7.1. Heterogeneity of Diabetes Mellitus.- 7.1.1. The Histocompatibility System (HLA) and Genetic Susceptibility to Diabetes Mellitus.- 7.1.2. Susceptibility to Viral Infection and Viral Infection in the Etiology of Diabetes Mellitus.- 7.1.5. Autoimmunity in Diabetes Mellitus.- 7.2. Insulin Secretion.- 7.2.1. Experimental Results in Animals: Hypothalamic Influences.- 7.2.2. Regulation in Man.- Effects of Intraportal and Peripheral Infusions of Glucagon on Insulin Secretion.- Effects of Secretin.- Effects of Hypocalcemia and Theophylline.- Plasma Insulin in Early Diabetes.- Plasma Insulin in Diabetes.- Measurement of Other Beta Cell Secretory Products: Proinsulin and C- Peptide.- Effects of Control of Diabetes on Insulin Secretion.- 7.3. Insulin Resistance and Insulin Receptors.- 7.3.1. Insulin Resistance and Sensitivity.- 7.3.2. Insulin Receptors.- Insulin Receptors and Insulin Resistance in Diabetes.- Insulin-Binding in Other Clinical Conditions.- 7.3.3. Autoantibodies to Insulin Receptors.- 7.4. Diabetes and Exercise.- 7.4.1. Exercise and Diabetes Mellitus in Man.- 7.4.2. Effect of Exercise in Depancreatized Dogs.- 7.4.3. Effect of in Vitro Contracting Skeletal Muscle on Glucose Uptake.- 7.5. Diabetes and Pregnancy.- 7.5.1. Special Considerations.- 7.5.2. Management of Pregnancy in Diabetic Patients.- 7.6. Acidosis in Diabetes.- 7.6.1. Diabetic Ketoacidosis.- Diabetic Ketoacidosis and Low-Dose Insulin Therapy.- 7.6.2. Lactic Acidosis.- 7.7. Long-Term Complications.- 7.7.1. Diabetic Neuropathy.- Evidence of Genetic Heterogeneity.- Radiculopathy.- Peripheral Neuropathy.- Diabetic Amyotrophy.- Autonomic Neuropathy.- Myoinositol Metabolism.- Experimental Diabetes and Diabetic Neuropathy.- 7.7.2. Diabetic Microangiopathy.- Muscle Capillary Basement Membrane Thickening.- Diabetic Microangiopathy and Intravascular Factors.- Diabetic Retinopathy.- Renal Changes and Nephropathy.- 7.7.3. Bone Mass in Diabetes Mellitus.- 7.8. Treatment of Diabetes Mellitus.- 7.8.1. General Considerations.- 7.8.2. Glycosylated Hemoglobin and Diabetic Control.- 7.8.3. Diet.- 7.8.4. Insulin.- Chronic Insulin Therapy.- Insulin Antibodies.- Lipoatrophy.- Insulin Delivery Systems.- 7.8.5. Transplantation.- 7.8.6. Oral Hypoglycemic Agents.- References.- 8 Glucagon and Somatostatin.- 8.1. Anatomy of the Islets of Langerhans.- 8.1.1. Topographical Relationships of the Islet Cells.- 8.1.2. Vascular and Neural Relationships.- 8.1.3. "Paracrine" Relationships.- 8.1.4. Subcellular Specializations.- Tight Junctions.- Gap Junctions.- 8.2. Structure-Function Relationships of Glucagon.- 8.2.1. Biological Structure-Function Relationships.- 8.2.2. Immunologic Structure-Function Relationships.- 8.3. Pancreatic and Extrapancreatic Immunoreactive Glucagons.- 8.3.1. Immunoreactive Glucagon Fractions in Tissue Extracts.- Pancreas.- Stomach.- Intestine.- Salivary Gland.- 8.3.2. Biosynthesis of Pancreatic Glucagon.- 8.3.3. Extrapancreatic A Cells and Glucagon Secretion.- A Cells.- Glucagon.- 8.3.4. Immunoreactive Glucagon in Plasma.- 8.4. Glucagon Metabolism, Clearance, and Degradation.- 8.5. Actions of Glucagon.- 8.5.1. Mechanisms.- Receptor Binding.- Adenylate Cyclase Activation.- Glycogenolysis.- Gluconeogenesis.- Ketogenesis.- Effects on Lipids.- 8.5.2. Physiology.- Glycogenolysis.- Gluconeogenesis.- 8.6. Control of Glucagon Secretion.- 8.6.1. Control by Nutrients.- Glucose.- Amino Acids.- Free Fatty Acids.- 8.6.2. Influence of Hormones.- Gastrointestinal Hormones.- Neurotensin and Substance P.- Bombesin.- Other Factors.- 8.6.3. Neural Control.- Hypothalamic Influences.- Adrenergic Stimulation-Stress and Exercise.- Dopaminergic Influence.- Serotonin.- 8.7. Glucagonlike Immunoreactivity (Enteroglucagon).- 8.8. Somatostatin.- 8.8.1. Distribution in Tissues.- Central Nervous System.- Gastrointestinal Tract.- Pancreas.- 8.8.2. Pancreatic Somatostatin Release.- 8.8.3. Mechanism of Action.- 8.8.4. Abnormalities of Somatostatin.- 8.8.5. Somatostatin Degradation.- 8.8.6. Somatostatin Analogues.- 8.9. Glucagon in Clinical Medicine.- 8.9.1. Diabetes Mellitus.- A-Cell Function in Diabetes.- Effect of Insulin on A-Cell Function in Juvenile-Type Diabetes Mellitus.- Effect of Insulin on Adult-Onset Diabetics.- Pathophysiologic Importance of Glucagon in Insulin Deficiency.- Controversy Concerning the Importance of Glucagon in Diabetes Mellitus.- Controversy Concerning the Role of Glucagon in the Presence of Insulin.- Mechanism of Somatostatin-Induced Amelioration of Diabetic Hyperglycemia.- 8.9.2. Glucagonoma.- 8.9.3. Nondiabetic Hyperglucagonemia.- 8.9.4. Glucagon Deficiency.- References.- 9 Recent Advances in Body Fuel Metabolism.- 9.1. Introduction.- 9.2. Glucose Metabolism.- 9.2.1. Is Glucagon Essential in Diabetes?.- Somatostatin-Induced Hypoglucagonemia.- Pancreatectomized Man.- 9.2.2. Effects of Hyperglucagonemia.- Normal Man.- Diabetes.- Uremia.- 9.2.3. Glucose Production: Gluconeogenesis from Alanine.- 9.2.4. The Counterregulatory Response to Hypoglycemia.- 9.3. Ketone and Fatty Acid Metabolism.- 9.3.1. Hormonal Control of Ketogenesis.- 9.3.2. Role of Malonyl-Coenzyme A.- 9.3.3. Hypoketonemic Action of Alanine.- 9.4. Amino Acid Metabolism.- 9.4.1. Origin of Alanine Synthesized in Skeletal Muscle.- 9.4.2. Metabolic Fate of Glutamine Utilized by Intestine.- 9.5. Fuel Metabolism in Exercise.- 9.5.1. Influence of Glucose Ingestion before Exercise.- 9.5.2. Influence of Ethanol Ingestion.- 9.5.3. Glucose-Sparing Effect of Free Fatty Acids.- 9.5.4. Interaction of Exercise and Insulin in Diabetes 376.- References.- 10 What's New in Obesity: Current Understanding of Adipose Tissue Morphoiogy.- 10.1. Introduction.- 10.2. Techniques for Measuring Adipocyte Size and Number.- 10.2.1. Intact Tissue.- 10.2.2. Osmium-Fixed Tissue.- 10.2.3. Adipocyte Suspensions.- 10.2.4. Advantages and Disadvantages of Counting Techniques.- 10.3. Cellularity of Adipose Tissue in Man and Animals.- 10.3.1. Development of Adipose Cellularity in Man.- 10.3.2. Adipose Cellularity in Laboratory Rodents.- 10.3.3. Cellularity in Human Obesity.- 10.3.4. Cellularity in Animal Obesity.- 10.4. How Constant Is Adipocyte Number?.- 10.4.1. Stability of Cell Number.- 10.4.2. Changes in Cell Number.- 10.5. How Are New Adipocytes Formed?.- 10.6. Significance of Cell Size and Number in Energy Regulation.- References.- 11 Divalent Ion Metabolism.- 11.1. Introduction.- 11.2. Vitamin D.- 11.2.1. Introduction.- 11.2.2. Metabolism and Transport of 25-Hydroxy-Vitamin Dg.- 11.2.3. Regulation of 25-Hydroxy-Vitamin Dg-la- Hydroxylase and Generation of 1,25-Dihydroxy- Vitamin Dg.- 11.2.4. Measurement of Vitamin D Metabolites in Plasma.- 11.2.5. Actions of Vitamin D.- Effects on Phosphate Homeostasis and Absorption.- Actions of Vitamin D on the Kidney.- Effect of Vitamin D on the Parathyroid Glands.- 11.2.6. Biological Actions of 24,25-Dihydroxy-Vitamin Dg..- 11.2.7. Metabolism and Degradation of Vitamin D.- 11.2.8. Intestinal Calcium Absorption and Mechanism of Adaptation to a Low-Calcium Diet.- Methods of Assessing Calcium Absorption.- 11.3. Clinical Disorders That Involve Altered Vitamin D Metabolism.- 11.3.1. Abnormal Metabolism of 25-Hydroxy-Vitamin Dg.- Liver Disease.- Anticonvulsants.- Nephrotic Syndrome.- 11.3.2. Defective Production of 1,25-Dihydroxy-Vitamin Dg.- Renal Osteodystrophy.- Diabetes MeUitus.- Osteomalacia Related to Mesenchymal Tumor.- Fanconi Syndrome.- 11.3.3. Other Disorders with Uncertain Relationship to Vitamin D.- Neonatal Hypocalcemia.- Familial Hypophosphatemic Vitamin-D- Resistant Rickets.- "Itai-Itai" Disease.- Metabolic Acidosis.- Glucocorticoid Treatment.- 11.3.4. Endocrine Disorders with Altered Production of I, 25-Dihydroxy-Vitamin Dg.- 11. 3.4.1. Hypoparathyroidism.- Pseudohypoparathyroidism.- 11.4. Phosphorus Metabolism.- 11.4.1. Regulation of Phosphorus by the Kidney.- Effect of Restriction of Phosphorus Intake.- Adaptation to High-Phosphorus Intake.- Effect of Parathyroid Hormone.- Effects of Estrogen on Phosphate Metabolism.- Growth Hormone and Renal Phosphate Reabsorption.- Other Factors That Affect Renal Handling of Phosphorus.- 11.4.2. Phosphate-Depletion Syndrome.- References.- 12 Metabolism of Amino Acids and Organic Acids.- 12.1. Pyruvate Metabolism and Its Disorders.- 12.2. Pyruvate Metabolism and Its Regulation.- 12.2.1. Pyruvate Kinase.- 12.2.2. The Pyruvate Dehydrogenase Complex.- 12.2.3. Pyruvate Carboxylase.- 12.2.4. Phosphoenolpyruvate Carboxykinase and the Malate Shutde.- 12.2.5. Metabolic Regulation of Pyruvate Metabolism.- 12.3. Specific Disorders of Pyruvate Metabolism.- 12.3.1. Erythrocyte Pyruvate Kinase Deficiency.- 12.3.2. Pyruvate Carboxylase Deficiency.- 12.3.3. Phosphoenolpyruvate Carboxykinase Deficiency.- 12.3.4. Pyruvate Dehydrogenase Complex Mutants.- Pyruvate Decarboxylase Deficiency.- Dihydrolipoyl Transacetylase Deficiency.- Dihydrolipoyl Dehydrogenase Deficiency.- 12.3.5. Pyruvate Dehydrogenase Phosphatase Deficiency.- 12.3.6. Decreased Activity of Pyruvate Oxidation in Patients with Friedreich's Ataxia and OtherNeuromuscular Diseases.- References.

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