The Year in Metabolism 1975-1976

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