Disorders of Lipid Metabolism, Softcover reprint of the original 1st ed. 1990

For the past 30 years I have been teaching lipid biochemistry to'inedical students, graduate students, and undergraduate students. The major topics covered in my courses were fatty acids, prostaglandins, leukotrienes, phospholipids, glyco­ lipids, triacylglycerols, cholesterol, bile acids, and plasma lipoproteins. Empha­ sis was placed on the regulation and disorders of lipid metabolism. The latter included hyperlipidemias, atherosclerosis, and alcohol-induced liver damage. In this volume, I have chosen to focus on the disorders of lipid metabolism at a level appropriate both for medical students and for graduate and undergradu­ ate students majoring in the biological sciences. The biochemistry, nutrition, genetics, and cell biology aspects of lipids and lipid metabolism will be covered as they relate to lipid disorders. I am not aware of any textbook that integrates the disorders of lipid metabolism in this manner. Chapter 1 includes a brief discussion of the basic structures, properties, and metabolism of lipids. This chapter is not very detailed, since the material covered is available in basic textbooks on biochemistry. The major fpcus of this volume is the various lipid disorders, with emphasis on polyunsaturated fatty acids, the molecular biology and pathogenesis of the hyperlipidemias, dietary and drug therapy for the hyperlipidemias, and alcohol-induced liver damage. The material presented has been obtained from several textbooks on biochemistry and from a variety of recent articles in the scientific literature.

1 Disorders of Lipid Digestion and Absorption.- 1.1. Introduction to the Structures and Properties of Lipids.- 1.2. Digestion and Absorption of Lipids.- 1.2.1. Lingual and Gastric Digestion.- 1.2.2. Intestinal Digestion.- 1.3. Characteristics of Disorders of Lipid Digestion and Absorption.- References.- 2 Disorders of Fatty Acid Metabolism.- 2.1. General Aspects of Fatty Acid Metabolism.- 2.1.1. Oxidation of Fatty Acids.- 2.1.2. Role of Carnitine.- 2.1.3. Deficiency of CAT-I and Carnitine.- 2.2. ? Oxidation of Fatty Acids.- 2.3. Disorders of Propionic Acid Metabolism.- 2.3.1. Propionyl-CoA Carboxylase Deficiency.- 2.3.2. Methylmalonic Acid Acidemias.- 2.4. ? and ? Oxidation of Fatty Acids.- 2.5. Refsum’s Disease.- 2.6. Zellweger’s Syndrome.- 2.7. Ketogenesis, Ketosis, and Ketoacidosis.- 2.8. Synthesis of Fatty Acids.- 2.8.1. Elongation of Fatty Acids.- 2.8.2. Formation of Nonessential Monoenoic and Polyenoic Fatty Acids.- 2.9. Essential Fatty Acid Deficiency.- References.- 3 Disorders of Excessive Alcohol Intake: Hypoglycemia, Fatty Liver, and Liver Cirrhosis.- 3.1. Introduction to the Biochemical Effects of Alcohol Intake.- 3.2. Metabolism of Alcohol.- 3.3. Effects of Alcohol Intake on Fatty Acid Metabolism.- 3.4. Alcoholic Hypoglycemia.- 3.5. Alcoholic Hepatitis and Liver Cirrhosis.- 3.6. Effects of Alcohol on the CNS.- 3.7. Effects of Acetaldehyde.- 3.8. Effects of Alcohol on the Heart.- 3.9. Alcohol-Drug Interactions.- 3.10. Alcohol Withdrawal Symptoms.- 3.11. Alcohol Intake and Heart Disease.- References.- 4 Disorders of Cholesterol Metabolism: Cholesterol Storage Diseases.- 4.1. Overall Cholesterol Balance in Humans.- 4.2. Synthesis of Cholesterol.- 4.3. Conversion of Cholesterol to Bile Acids.- 4.4. Abnormalities of Cholesterol Metabolism.- 4.4.1. Wolman’s Disease.- 4.4.2. Cholesterol Ester Storage Disease.- 4.4.3. Cerebrotendinous Xanthomatosis.- 4.4.4. ?-Sitosterolemia with Xanthomatosis.- 4.4.5. Pseudohomozygous Familial Hypercholesterolemia.- 4.4.6. Familial LCAT Deficiency.- 4.5. Cholelithiasis (Gallstones).- References.- 5 Disorders of Lipoprotein Metabolism: Dyslipoproteinemias.- 5.1. Plasma Lipoproteins and Apoproteins: General Aspects.- 5.2. Structure and Function of Apoproteins.- 5.2.1. ApoA-I.- 5.2.2. ApoA-II.- 5.2.3. ApoA-IV.- 5.2.4. ApoB-100 and ApoB-48.- 5.2.5. ApoC-I.- 5.2.6. ApoC-II.- 5.2.7. ApoC-III.- 5.2.8. ApoE.- 5.3. Metabolism of Lipoproteins.- 5.3.1. Lipoprotein Lipase.- 5.3.2. Hepatic Lipase.- 5.3.3. Metabolism of Chylomicrons.- 5.3.4. Metabolism of Very-Low-Density Lipoproteins.- 5.3.5. Metabolism of High-Density Lipoproteins.- 5.4. LDL, LDL Receptor, and HMGR.- 5.4.1. Metabolism of LDL.- 5.4.2. Structure of LDL and the LDL Receptor.- 5.4.3. Variant of the LDL.- 5.4.4. Synthesis of the LDL Receptor.- 5.4.5. The LDL Receptor mRNA and Gene.- 5.4.6. Mutations of the LDL Receptor.- 5.4.7. Structure of HMGR.- 5.4.8. Synthesis of HMGR.- 5.4.9. HMGR mRNA and Gene.- 5.4.10. Coordinate Regulation of HMGR and the LDL Receptor.- 5.5. Pathogenesis of Hyperlipoproteinemias.- 5.6. Factors Leading to Hyperlipidemias.- 5.7. Mechanisms of Hyperlipidemias.- 5.7.1. Defects in Lipoprotein Lipase and ApoC-II.- 5.7.2. Defects in LDL Clearance.- 5.7.3. Defects in ApoE and in Remnant Removal.- 5.8. Lipoprotein Metabolism in Diabetes.- 5.9. Hypolipoproteinemias.- 5.9.1. HDL Deficiency (Tangiers Disease).- 5.9.2. LCAT Deficiency.- References.- 6 Cholesterol, Lipoproteins, and Atherosclerosis.- 6.1. Atherosclerosis.- 6.1.1. Early History of Atherosclerosis.- 6.1.2. Experimental Atherosclerosis.- 6.1.3. Epidemiological Data.- 6.2. Survey Studies: Cholesterol and CHD.- 6.3. Alcohol Intake and CHD.- 6.4. Drug Therapy for Hyperlipidemias.- 6.5. Postulated Mechanisms of Atherosclerosis.- References.- 7 Dietary Management of Elevated Blood Lipids.- 7.1. Dietary Lipids, Hyperlipidemia, and Heart Disease.- 7.1.1. Dietary Lipids.- 7.1.2. Effects of Dietary Fatty Acids on Plasma Lipids and Lipoproteins.- 7.1.3. Effects of Dietary Fatty Acids on Platelet Aggregation.- 7.1.4. Role of Dietary ?-3 Fatty Acids in Heart Disease.- 7.1.5. Conversion of Polyunsaturated Fatty Acids to Prostaglandins.- 7.1.6. Relation of Dietary Lipids to CHD.- 7.1.7. Influence of Egg Consumption on Blood Cholesterol.- 7.1.8. Exercise and Heart Disease.- 7.1.9. Fad Diets and Other Dietary Agents.- 7.1.10. Excessive Vitamin Intake.- 7.2. Biochemical Effects of Polyunsaturated Fatty Acids.- 7.2.1. Types of Polyunsaturated Fatty Acids.- 7.2.2. ?-6 Fatty Acids and Plasma Lipids.- 7.2.3. Membrane Fatty Acid Composition and Lipoprotein Metabolism.- 7.2.4. ?-3 Fatty Acids and Plasma Lipids.- 7.2.5. Hypolipidemic Mechanisms of the ?-3 Fatty Acids.- 7.3. Platelet and Blood Vessel Prostaglandins Derived from Dietary Polyunsaturated Fatty Acids.- 7.4. Effects of Polyunsaturated Fatty Acids on Platelet Function.- 7.4.1. Linoleic Acid.- 7.4.2. Linolenic Acid.- 7.4.3. Eicosapentenoic Acid.- 7.5. Platelet Lipid Composition.- 7.6. Platelet and Vascular Function.- 7.7. Mechanisms of Fatty Acid Effects.- 7.8. Possible Risks and Side Effects from Increased Amounts of Dietary Polyunsaturated Fatty Acids.- 7.8.1. ?-6 Fatty Acids.- 7.8.2. ?-3 Fatty Acids.- References.- 8 Drug Therapy for Hyperlipidemias: Lipid-Lowering Drugs and Antithrombic and Fibrinolytic Drugs.- 8.1. Lipid-Lowering Drugs.- 8.2. Combined Drug Therapy.- 8.3. Antithrombic Drugs.- 8.3.1. Endothelial Injury.- 8.3.2. Platelet Adherence and Aggregation.- 8.3.3. Thrombin and Fibrin Formation.- 8.3.4. Plasmin Formation and Fibrinolysis.- 8.4. Fibrinolytic Drugs.- 8.5. Mechanisms of Action of Antithrombic Drugs.- 8.6. Arachidonic Acid Release Inhibitors.- 8.7. Drugs That Inhibit cAMP Formation in Platelets.- 8.8. Membrane-Active Drugs.- 8.9. Anticoagulants and Other Drugs.- 8.10. Antithrombic Drugs for Treatment of CHD.- 8.10.1. Anticoagulant Therapy for MI.- 8.10.2. Long-Term Anticoagulant Therapy for MI.- 8.10.3. Platelet Inhibitors and Acute MI.- References.- 9 Lung Surfactant Deficiency: Respiratory Distress Syndrome of the Newborn.- 9.1. Early History.- 9.2. Properties of DPPC.- 9.3. Lung Surfactant.- 9.4. Synthesis of Lung Surfactant Phospholipids.- 9.5. Hormonal Regulation of the Synthesis of Lung Surfactant.- 9.6. Therapy for RDS.- References.- 10 Sphingolipidoses: Gangliosidoses, Tay-Sachs Disease, and Sandhoff’s Disease.- 10.1. Early History.- 10.2. Genetic Defects.- 10.3. Sphingolipids.- 10.3.1. Biosynthesis of the Sphingolipids.- 10.3.2. Enzymatic Degradation of the Gangliosides.- 10.3.3. Distribution of Gangliosides in the Brain.- 10.3.4. Types and Clinical Features of GM2 Gangliosidoses.- 10.4. Overview of the Sphingolipidoses.- 10.5. Therapeutic Approaches for the Sphingolipidoses.- References.