The Year in Metabolism 1975-1976

ISBN-13: 9781468476583 / Angielski / Miękka / 2012 / 353 str.

Norbert Freinkel

Opis

It is unclear, and really no longer relevant, whether the information explosion that we now contend with has been fostered by the growth of specialization and subspecialization in medicine, or vice versa. What is clear is that the two are mutually supportive and constitute what would be in endocrine parlance a short-loop positive feedback system. As a result, for most areas of medicine, even the subspecialist in that area has a problem in maintaining currency, the more general specialist has substan tial difficulty in doing so, and the generalist is tempted to abandon the effort altogether. Nevertheless, for all, both the internal pressures of conscience and self-esteem and the external pressures generated by peer review, recertifi cation, and subspecialty boards create the need for continuous self-educa tion. We are, therefore, in an era in which the means of dissemination of new information deserves as much creative attention as does its acquisition."

Spis treści

1 Hormone Receptors, Cyclic Nucleotides, and Control of Cell Function.- 1.1. Introduction.- 1.2. Receptor Systems.- 1.2.1. General Regulatory Mechanisms and Kinetics.- 1.2.1.1. Physiological Regulation of Receptors.- 1.2.2. Opiate Receptors.- 1.2.2.1. Endogenous Peptides Active at the Opiate Receptor.- 1.2.3. ?-Adrenergic Receptors.- 1.2.3.1. Regulation of ?-Andrenergic Receptors.- 1.2.4. Calcitonin Receptors.- 1.2.5. Parathyroid Hormone Receptors.- 1.2.6. Vasopressin Receptors.- 1.2.7. Insulin, Nonsuppressible Insulinlike Activity, Somatomedin, Nerve Growth Factor, and Epidermal Growth Factor Receptors.- 1.2.7.1. Insulin and Nonsuppressible Insulinlike Activity Receptors.- 1.2.7.2. Somatomedin, Nerve Growth Factor, and Epidermal Growth Factor Receptors.- 1.2.8. Metabolic Defects Involving Receptors.- 1.2.8.1. Receptor Deficiency.- 1.2.8.2. Immunopathic Receptor Disorders.- 1.3. Regulation of Adenylate Cyclase.- 1.3.1. General.- 1.3.2. Guanine Nucleotides and Regulation of Adenylate Cyclase.- 1.3.3. Toxins.- 1.4. Cyclic 3?,5?-Adenosine Monophosphate Concentration in Tissue and Protein Kinase Activation.- 1.4.1. General.- 1.4.2. Protein Kinases.- 1.4.3. Regulation of Cyclic Nucleotide Phosphodiesterase Activity.- 1.4.3.1. Cyclic Nucleotide Phosphodiesterase in the Physiology of Vision.- 1.5. Cyclic Nucleotides in the Extracellular Fluids.- 1.5.1. General.- 1.5.2. Plasma Cyclic Nucleotides—Production Rates and Clearance.- 1.5.3. Cyclic 3?,5?-Adenosine Monophosphate in Cerebrospinal Fluid.- 1.5.4. Urinary Excretion of Cyclic 3?,5?-Adenosine Monophosphate.- 1.5.5. Parathyroid Hormone and Renal Clearance of Cyclic 3?,5?-Adenosine Monophosphate.- 1.5.5.1. Pseudohypoparathyroidism.- 1.5.6. Other Factors and Hormones That Affect Urinary Cyclic 3?,5?-Adenosine Monophosphate Excretion.- References.- 2 Diabetes Mellitus.- 2.1. Introduction.- 2.2. Heterogeneity in Etiology and Pathogenesis.- 2.2.1. Heterogeneity of Heredity.- 2.2.1.1. Patterns of Inheritance.- 2.2.1.2. Histocompatibility Typing.- 2.2.1.3. Twin Studies.- 2.2.1.3a. Prevalence of Diabetes.- 2.2.1.3b. HLA Typing.- 2.2.1.4. Autoimmunity.- 2.2.2. Environmental Factors.- 2.2.2.1. Viral Factors—Multiple.- 2.2.2.2. Nutritional Factors.- 2.2.3. Insulin Secretion.- 2.2.3.1. Heterogeneity of Insulin Responses to Glucose in the Maturity-Onset Type of Diabetes.- 2.2.3.2. Insulin Resistance.- 2.2.3.2a. In Vivo.- 2.2.3.2b. In Vitro—Receptor-Binding Studies.- 2.2.3.3. Glucose Receptors—d-Glucose Anomers.- 2.2.4. Glucagon Secretion—Somatostatin.- 2.3. Measurement of Insulin Secretory Products.- 2.4. Acute Complications.- 2.4.1. Ketoacidosis.- 2.4.1.1. Low-Dose Insulin Treatment.- 2.4.1.2. Bicarbonate Therapy.- 2.4.1.3. 2,3-Diphosphoglycerate and Phosphate Therapy.- 2.4.2. Alcoholic Ketoacidosis.- 2.4.3. Lactic Acidosis.- 2.5. Long-Term Complications.- 2.5.1. Diabetic Neuropathy.- 2.5.2. Accelerated Aging.- 2.5.3. Diabetic Microangiopathy.- 2.5.3.1. Basement Membrane Thickening.- 2.5.3.2. Diabetic Glomerulosclerosis.- 2.5.3.2a. Human.- 2.5.3.2b. Experimental.- 2.5.3.3. Diabetic Retinopathy and Intravascular Factors.- 2.5.4. Evidence for Heterogeneity.- 2.5.5. Changes in Hemoglobin Components.- 2.5.5.1. Changes in Concentration of Hemoglobin Alc.- 2.5.5.2. Changes in Concentration of 2,3-DPG.- References.- 3 Glucagon.- 3.1. Immunoreactive Glucagon in Tissues and Plasma.- 3.1.1. Primary Structure of Glucagon.- 3.1.2. Biosynthesis.- 3.1.3. Plasma Immunoreactive Glucagon.- 3.1.4. Tissue Immunoreactive Glucagon.- 3.2. Glucagon Metabolism—Clearance and Degradation.- 3.3. Actions of Glucagon on the Liver.- 3.3.1. Glucagon and Hepatic Glucose Production.- 3.3.2. Glucagon and Ketogenesis.- 3.4. Physiological Roles of Glucagon and Insulin in Fuel Homeostasis—The Concept of a Bihormonal Unit.- 3.5. Proposed Mechanisms of Glucagon Action.- 3.5.1. Glucagon and Its Receptors.- 3.5.2. Mechanism of Adenylate Cyclase Activation.- 3.6. Control of Glucagon Secretion.- 3.6.1. Glucose.- 3.6.2. Amino Acids.- 3.6.3. Free Fatty Acids.- 3.6.4. Cyclic 3?,5?-Adenosine Monophosphate.- 3.6.5. Hormones.- 3.6.6. Sympathetic Nerves.- 3.6.7. Exercise.- 3.6.8. Severe Stress.- 3.6.9. Acetylcholine.- 3.6.10. Calcium.- 3.6.11. Somatostatin.- 3.7. Studies of Glucagon Physiology Using Somatostatin.- 3.8. Microanatomical Organization of the Islets of Langerhans.- 3.8.1. Functional Subdivisions of the Islets and the Role of the Insular D-Cell.- 3.8.2. Ultrastructural Features of Islet Cells.- 3.8.2.1. Exocytosis.- 3.8.2.2. Tight Junctions.- 3.8.2.3. Gap Junctions.- 3.9. Extrapancreatic Glucagon.- 3.9.1. Morphological and Biochemical Studies.- 3.9.2. Gastric Glucagon Secretion.- 3.10. Diabetes Mellitus.- 3.10.1. A-Cell Function in Human Diabetes.- 3.10.2. The Bihormonal Abnormality Hypothesis.- 3.10.3. Evidence Against the Bihormonal Abnormality Hypothesis.- 3.10.4. Mechanism of Diabetic Hyperglucagonemia in Man.- 3.11. A-Cell Function in Prediabetes.- 3.12. Catabolic Diseases.- 3.13. Glucagonoma.- References.- 4 Recent Developments in Body Fuel Metabolism.- 4.1. Introduction.- 4.2. Glucose Metabolism.- 4.2.1. Glucose Disposal.- 4.2.2. Insulin—Glucagon Interaction in Glucose Disposal.- 4.3. Protein and Amino Acid Metabolism.- 4.3.1. Protein Feeding and Repletion of Muscle Nitrogen.- 4.3.2. Amino Acid Output from Muscle in the Fasting State.- 4.4. Fatty Acid and Ketone Metabolism.- 4.4.1. Substrate and Enzymatic Factors in Ketogenesis.- 4.4.2. Hormonal Regulation of Ketogenesis.- 4.4.3. Ketone Accumulation in Starvation.- 4.4.4. Ketone–Alanine Interactions.- 4.5. Fuel Metabolism in Exercise.- 4.5.1. Brief and Prolonged Exercise in Normal Subjects.- 4.5.2. Exercise in Diabetes Mellitus.- References.- 5 Recent Endocrine and Metabolic Investigations Relevant to Obesity.- 5.1. Introduction.- 5.2. Insulin.- 5.2.1. Carbohydrate Resistance in Obesity.- 5.2.2. Studies on Insulin Receptors.- 5.2.3. Insulin as a Controller of Appetite and Hunger.- 5.3. Thermogenesis and Thyroid Function.- 5.4. The Gastrointestinal Tract.- 5.4.1. Jejunoileal Shunts.- 5.4.2. Cholecystokinin and Satiety.- 5.5. Appetite and Substrate Utilization.- 5.5.1. Protein-Sparing and Ketogenic Diets.- 5.5.2. Inhibition of Fatty Acid Synthesis.- References.- 6 Disorders of Lipid and Lipoprotein Metabolism.- 6.1. Introduction.- 6.2. Lipoprotein Structure and Metabolism.- 6.2.1. Introduction.- 6.2.2. Very-Low-Density Lipoproteins.- 6.2.3. Low-Density Lipoproteins.- 6.2.4. High-Density Lipoproteins.- 6.3. Hyperlipidemias—Definition and Classification.- 6.3.1. “Normal” Levels of Plasma Lipids.- 6.3.2. Classification by Lipid Elevation.- 6.3.3. Classification by Type of Hyperlipoproteinemia.- 6.3.4. Genetic Classification.- 6.4. Familial Hypercholesterolemia.- 6.4.1. Introduction.- 6.4.2. Pathogenesis.- 6.4.3. Diagnosis and Classification.- 6.4.4. Portacaval Shunt Surgery and Homozygous Familial Hypercholesterolemia.- 6.4.5. Other Therapy.- 6.5. Type III Hyperlipoproteinemia.- 6.6. Familial Lecithin: Cholesterol Acyltransferase Deficiency.- 6.7. Chronic Renal Failure and Hyperlipidemia.- 6.8. Diabetes Mellitus and Hyperlipidemia.- 6.9. Treatment of Hyperlipidemia.- 6.9.1. Diet.- 6.9.2. The Coronary Drug Project.- 6.9.3. Primary Prevention of Ischemic Heart Disease.- References.- 7 Metabolism of Amino Acids and Organic Acids.- 7.1. Introduction.- 7.2. Hyperammonemia and Urea Cycle Enzymes.- 7.2.1. Ammonia Formation and Removal.- 7.2.2. Ammonia Intoxication.- 7.2.3. Biochemical and Clinical Variations in Ornithine Transcarbamylase Deficiency.- 7.2.4. Possible Modes of Successful Therapy for Severe Ornithine Transcarbamylase Deficiency.- 7.2.5. Pathogenesis of Hyperammonemia in Reye’s Syndrome.- 7.3. Inherited Defects of Cobalamin (Vitamin B12) Metabolism.- 7.3.1. Genetic Control of Vitamin Metabolism.- 7.3.2. Enumeration and Characterization of Specific Inherited Defects.- 7.3.3. Cobalamin Supplementation as Therapy—Some Caveats.- 7.3.4. Prenatal Diagnosis and Treatment of Methylmalonicacidemia.- 7.4. Use of Stable Isotopes in the Investigation of Disorders of Amino Acid and Organic Acid Metabolism.- 7.4.1. Stable Isotopes.- 7.4.2. Advances in Instrumentation: Combined Gas Chromatography-Mass Spectrometry and 13C Nuclear Magnetic Resonance.- 7.4.3. Biohazards.- 7.4.4. Recent Investigations with Stable Isotopes.- 7.4.4.1. [13C]Valine Metabolism in a Patient with Methylmalonicacidemia, Using 13C-NMR —Identification of Propionate as an Obligate Intermediate.- 7.4.4.2. Identification of a Minor Pathway of Isoleucine Metabolism.- 7.4.4.3. Use of Deuterated Phenylalanine and Tyrosine in Studies of Phenylketonuria In Vivo.- References.- (Section 7.1).- Hyperammonemia and Urea Cycle Enzymes (Section 7.2).- Inherited Defects of Cobalamin Metabolism (Section 7.3).- Stable Isotopes (Section 7.4).- 8 Disorders of Purine and Pyrimidine Metabolism.- 8.1. Introduction.- 8.1.1. Role of Gout and Hyperuricemia in Development of New Medical Concepts.- 8.1.1.1. Pathology Produced by Sparingly Soluble Substances.- 8.1.1.2. Concept of Genetic Heterogeneity in Causation of Disease.- 8.1.2. Insight into Cellular and Physiological Mechanisms Revealed by Mutations.- 8.1.2.1. Regulation of Purine Synthesis.- 8.1.2.2. Physiological Consequences of Failure To Repair DNA Damaged by Ultraviolet (UV) Light.- 8.1.2.3. Role of Purine and Pyrimidine Nucleotide Metabolism in Brain Function.- 8.1.2.4. Role of Purine and Pyrimidine Nucleotide Metabolism in Normal Development and Function of the Hematological System.- 8.1.2.5. Role of Purine Nucleoside Interconversion and Pyrimidine Metabolism in the Immune Response.- 8.1.2.6. Purine and Pyrimidine Biosynthesis as a Major Function of Carbon Dioxide Required by Mammalian Cells In Vitro.- 8.1.2.7. Use of Purine and Pyrimidine Mutants in Somatic Cell Genetics.- 8.2. Abnormalities of Purine Metabolism.- 8.2.1. Adenine Phosphoribosyltransferase Deficiency.- 8.2.2. Hypoxanthine-Guanine Phosphoribosyltransferase (HPRT) Deficiency.- 8.2.3. Adenosine Deaminase Deficiency.- 8.2.3.1. Range of Clinical Presentation.- 8.2.3.2. Radiographic Changes.- 8.2.3.3. Genetics.- 8.2.3.4. Enzymology of Adenosine Deaminase.- 8.2.3.5. Changes with Mitogenic Stimulation.- 8.2.3.6. Proposed Pathogenetic Mechanisms.- 8.2.3.7. Therapy.- 8.2.4. Mutations in Phosphoribosylpyrophosphate Synthetase.- 8.2.4.1. Increased Activity of Phosphoribosylpyrophosphate Synthetase.- 8.2.4.2. Decreased Activity of Phosphoribosylpyrophosphate Synthetase.- 8.2.5. Hereditary Xanthinuria from Xanthine Oxidase Deficiency.- 8.2.6. Evidence of Influence of Carbohydrate Metabolism on Purine Metabolism.- 8.3. Abnormalities in Serum Urate Concentration.- 8.3.1. Hyperuricemia.- 8.3.2. Effects of Hyperuricemia on Renal Function.- 8.3.3. Clinical Disorders Associated with Hypouricemia.- 8.3.4. Convenient Clinical Method for Evaluation of Uric Acid Production.- 8.4. Abnormalities of Pyrimidine Metabolism.- 8.4.1. Orotic Aciduria.- 8.4.1.1. Hereditary Orotic Aciduria.- 8.4.1.2. Orotic Aciduria from Defects in Urea Synthesis.- 8.4.1.3. Pharmacologically Induced Orotic Aciduria.- 8.4.2. Pyrimidine 5?-Nucleotidase Deficiency.- 8.4.2.1. Presentation.- 8.4.2.2. Biochemical Features.- 8.4.2.3. Genetics.- 8.4.3. Uridine Monophosphate Kinase Relative Deficiency.- 8.4.4. Carbamyl Phosphate Synthetase Deficiency.- 8.4.5. ?-Aminoisobutyric Acid Excretion.- 8.5. Regulatory Role of Cyclic Purine Nucleotides.- 8.5.1. Cyclic 3?,5?-Adenosine Monophosphate.- References.- 9 What’s New—Vitamins and Minerals.- 9.1. Introduction.- 9.2. Vitamin C.- 9.3. Vitamin D.- References.- 10 Nutrition, Growth, and Development.- 10.1. Introduction.- 10.2. Normal Nutrition.- 10.2.1. Nutrition and Cellular Growth.- 10.2.1.1. Specific Nutrient Deficiencies.- 10.2.2. Nutrition and Neurohormones.- 10.2.3. Nutrition and Pregnancy.- 10.2.4. Early Infant Nutrition.- 10.2.5. Nutrition and Muscle Metabolism.- 10.2.6. Interaction of Nutrition and the Endocrine System.- 10.3. Abnormal Nutrition.- 10.3.1. Parenteral Nutrition in Small Infants.- 10.3.2. Nutrition and Physical and Mental Development.- 10.3.3. Childhood Obesity.- 10.3.4. Nutrition and Cancer.- References.- Additional Selected Reading List.- 11 Metabolic Aspects of Renal Stone Disease.- 11.1. Introduction.- 11.2. Types of Renal Stones.- 11.3. Pathogenesis of Renal Stones.- 11.3.1. Basic Mechanisms of Stone Formation.- 11.3.2. Specific Causes of Renal Stone Disease.- 11.3.2.1. Hypercalciuria.- 11.3.2.2. Hyperoxaluria.- 11.3.2.3. Recurrent Urinary Tract Infections.- 11.3.2.4. Hyperuricosuria.- 11.3.2.5. Cystinuria.- 11.3.2.6. Xanthinuria.- 11.3.3. Idiopathic Stone Disease.- 11.4. Treatment and Prevention of Renal Stones.- 11.4.1. General Measures.- 11.4.1.1. Fluids.- 11.4.1.2. Diet.- 11.4.1.3. Urine pH.- 11.4.2. Specific Measures.- 11.4.2.1. Agents That Affect Calcium Excretion.- 11.4.2.2. Agents That Affect Oxalate Excretion.- 11.4.2.3. Agents That Affect Urate Excretion.- 11.4.2.4. Agents That Affect Cystine Excretion.- 11.4.2.5. Inhibitors of Stone Formation.- 11.5. Summary.- References.- 12 Metabolism and Metabolic Actions of Ethanol.- 12.1. Metabolism of Ethanol.- 12.2. The Hypermetabolic State Produced by Ethanol.- 12.3. Effects of Alcohol on the Liver and Development of Alcoholic Liver Injury.- 12.4. Interaction of Ethanol and Lipid Metabolism in Liver and Intestine.- 12.5. Acetaldehyde—Its Metabolism and Metabolic Effects.- References.