Disorders of Lipid Metabolism

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.