Biochemical Basis of Medicine

Part 1 Biochemistry of the Cell and Its Metabolism Chapter 1 Infrastructure of the Mammalian Cell 1.1 Introduction 1.2 Methods of Studying Cell Structure and Function 1.3 Ultrastructure of Typical Cells 1.4 Biochemical Functions of the Main Subcellular Components Chapter 2 Roles of Extracellular and Intracellular Membranes: Membrane Structure and Membrane Transport 2.1 Introduction 2.2 Membrane Composition 2.3 Membrane Structure 2.4 Membrane Functions 2.5 Membrane Transport Chapter 3 Role of Subcellular Organelles: Lysosomes 3.1 Origin of Lysosomal Enzymes 3.2 The Nature of the Lysosomal Enzymes 3.3 Investigational Methods and Properties of Lysosomal Enzymes 3.4 The Life Cycle of the Lysosome 3.5 Functions of Lysosomes in the Tissues 3.6 Lysosomes in Pathological Conditions Chapter 4 Role of Subcellular Organelles: Peroxisomes 4.1 Historical and Background 4.2 Structure of the Peroxisome 4.3 Enzyme Complement of the Peroxisomes 4.4 Biological Functions of Peroxisomes 4.5 Evolutionary History of Peroxisomes and Its Significance Chapter 5 Role of Subcellular Organelles: Metabolism in the Cytosol 5.1 Introduction 5.2 Preparation of the Cytosol 5.3 Composition of the Cytosol 5.4 Functions of the Cytosol Chapter 6 Role of Subcellular Organelles: Mitochondria and Energy Conservation 6.1 Introduction 6.2 Mitochondria in Typical Cells 6.3 Mitochondrial Structure 6.4 Composition of the Mitochondria 6.5 Functions of the Mitochondria 6.6 Relation of Mitochondrial Structure to Enzyme Activity and Function 6.7 Replication of Mitochondria Chapter 7 Role of Subcellular Organelles: Inter-Relationships of the Mitochondria and Cytosol 7.1 Membranes of the Mitochondria 7.2 Mitochondrial Transport Systems 7.3 Classification of Carrier Types 7.4 Classification of Carriers 7.5 Mode of Action of Typical Carriers 7.6 Roles of Carrier Systems in Metabolism Chapter 8 Role of Subcellular Organelles: The Nucleus 8.1 Introduction 8.2 Structure of the Nucleus 8.3 Metabolism in the Nucleus Chapter 9 Role of Subcellular Organelles: The Endoplasmic Reticulum 9.1 Nature of the Endoplasmic Reticulum 9.2 Relationship of the Endoplasmic Reticulum to Other Cellular Organelles 9.3 Separation of the Endoplasmic Reticulum By Ultracentrifugation—The 'Microsomes' or 'Microsomal Fraction' 9.4 Structure and Composition of the Endoplasmic Reticulum 9.5 Functions of the Smooth Membranes of the Endoplasmic Reticulum 9.6 Functions of the Rough Membranes of the Endoplasmic Reticulum—The RibosomesPart 2 Whole Body Metabolism Chapter 10 Nutrition: General Aspects 10.1 Introduction 10.2 Components of an Adequate Diet 10.3 Causes of Malnutrition 10.4 Nutritional Methodology 10.5 Nutritional Problems in Modern Society Chapter 11 Nutrition: Energy Requirements and the Supply of Energy by Oxidation of Foodstuffs 11.1 Energy Units 11.2 Energy Supply and Utilization 11.3 Basal Metabolism 11.4 Energy for Work Activity 11.5 Energy Supply from Foodstuffs Chapter 12 Nutrition: Proteins in the Diet 12.1 Introduction 12.2 Protein Turnover 12.3 Consequences of Removal of Protein from the Diet 12.4 Protein in Foodstuffs 12.5 Daily Protein Requirements 12.6 Protein Quality: First and Second Class Proteins and Essential Amino Acids 12.7 Concept of 'Biological Value' and 'Chemical Score' 12.8 Simulated Meat Foods 12.9 Consequence of Large Intakes of Protein 12.10 Nitrogen Balance Chapter 13 Nutrition: Dietary Fats 13.1 Introduction: Why Eat Fats? 13.2 Essential Fatty Acids 13.3 Human Response to Essential Fatty Acid Deficiency 13.4 Chain Elongation and Functions of Essential Fatty Acids 13.5 Diet and Heart Disease 13.6 Mode of Action of Polyunsaturated Fats in Reducing the Concentration of the Plasma Cholesterol 13.7 Value of Dietary Changes in the Prevention of Heart Disease Chapter 14 Nutrition: Vitamins 14.1 Introduction 14.2 Classification of the Vitamins 14.3 Vitamin Synthesis by Intestinal Bacteria 14.4 Storage of Vitamins 14.5 The Water-Soluble Vitamins: the B Groups of Vitamins and Vitamin C 14.6 The Fat-Soluble Vitamins Chapter 15 Nutrition: Inorganic Constituents of the Diet 15.1 Introduction 15.2 Metals Found in the Human Body 15.3 Factors Affecting Metal Requirements 15.4 Dietary Requirements for Metals 15.5 Anions in the Diet Chapter 16 Digestion and Absorption of Foodstuffs 16.1 Foods Digested and Absorbed in Man 16.2 Biochemical Changes in Ingested Foods and the Role of Digestive Organs 16.3 Enzymic Processes Involved in Digestion 16.4 The Digestive Secretions 16.5 Control of Digestive Secretions: The Gastrointestinal Hormones 16.6 Methods of Studying Absorption from the Intestine 16.7 Absorption Mechanisms 16.8 Carbohydrate Digestion and Absorption 16.9 Protein Digestion and Absorption 16.10 Fat Digestion and Absorption 16.11 Dietary Fiber 16.12 Bacteria Flora in the Gastrointestinal Tract 16.13 Malabsorption Syndromes Chapter 17 Hormones: A Summary of Their Structures and Functions 17.1 Introduction 17.2 The Role of the Second Messenger: Cyclic AMP 17.3 Structural Relationships of the Hypothalamus and the Pituitary Gland 17.4 the Hypothalamus—Anterior Pituitary—Target Organ Relationships 17.5 Hormones of the Hypothalamus 17.6 Hormones of the Anterior Pituitary (Adenohypophysis) 17.7 Hormones of the Posterior Pituitary (Neurohypophysis) 17.8 Hormones of the Pancreas 17.9 Hormones of the Thyroid 17.10 The Adrenals - the Adrenal Medulla 17.11 The Adrenal Cortex 17.12 Control of Metabolism by Hormones Chapter 18 Plasma Glucose and Its Regulation 18.1 Introduction 18.2 Maintenance of Glucose Concentration During Fasting Conditions 18.3 Insulin Release in the Fed Condition 18.4 Tissue Response to Increased Insulin and Glucose Plasma Concentration 18.5 The Role of Glucagon 18.6 Circulating Glucose Under Stress Conditions Chapter 19 Plasma Lipids and Their Regulation 19.1 Classification of Plasma Lipids 19.2 Lipid Transport in the Fed State 19.3 Lipid Transport in the Fasting State 19.4 Fatty Livers 19.5 Interaction and Interchange between Lipoproteins 19.6 Hyperlipoproteinaemias Chapter 20 Plasma Amino Acids and Utilization of Amino Acids by the Tissues 20.1 How Does Man Utilize Amino Acids? 20.2 The Effect of a Protein Meal on Plasma Amino Acid Concentrations 20.3 The Utilization of Branched-Chain Amino Acids in Muscle and Formation of Alanine 20.4 The Induction of Amino Acid Catabolizing Enzymes 20.5 Amino Acid Imbalance 20.6 Hormonal Regulation of Plasma Amino Acids Chapter 21 Plasma Electrolytes 254 21.1 Electrolyte Composition of Normal Plasma 21.2 Water Compartments of the Body 21.3 The Osmolarity of the Fluid Compartment and Its Regulation 21.4 Changes in the Plasma Concentrations of Specific Electrolytes Chapter 22 Plasma Calcium and Phosphate: Regulation By Vitamin D and Parathyroid Hormone 22.1 Introduction: Importance of Calcium and Phosphate in the Animal Body 22.2 Plasma Calcium 22.3 Dietary Calcium and Phosphate and Calcium Kinetics 22.4 Factors Regulating Calcium Absorption 22.5 Vitamin D 22.6 Conversion of Vitamin D3 to 1,25-Dihydroxy-Vitamin-D3 22.7 Mode of Action of 1,25-Dihydroxy-Vitamin-D3 22.8 Parathyroid Hormone 22.9 Calcitonin 22.10 Inter-Relationships of Vitamin D, Parathyroid Hormone and Calcitonin in the Regulation of Plasma Calcium Chapter 23 Starvation 23.1 Energy Storage 23.2 Phases of Starvation 23.3 Interprandial Phase 23.4 Postabsorptive Phase (Overnight Fast) 23.5 Prolonged Starvation 23.6 Clinical Aspects of Starvation—Anorexia NervosaPart 3 Specialized Metabolism of Tissues Chapter 24 Blood: Erythropoiesis—Role of Folate and Vitamin B12 24.1 Normal Erythropoiesis and Site of Formation of Abnormal Cells In Conditions of Folate and Vitamin B12 Deficiencies 24.2 Macrocytic Anaemias 24.3 Causes of Folate Deficiency 24.4 Absorption of Folate 24.5 Causes of Vitamin B12 Deficiency 24.6 Absorption and Transport of Vitamin B12 24.7 Inter-Relationships of Folate and Vitamin B12 24.8 Mode of Action of Folic Acid 24.9 Mode of Action of Vitamin B12 24.10 Metabolic Inter-Relationships of Folate and Vitamin B12 in 'Methyltetrahydrofolate Sink' Hypothesis 24.11 Possible Relationships of Folate and Vitamin B12 Deficiencies to Anemias 24.12 Neurological Damage in Vitamin B12 Deficiency Chapter 25 Blood: Metabolism in the Red Blood Cell 25.1 Introduction 25.2 Role of Glycolysis and the Pentose-Shunt Pathways 25.3 Utilization of ATP in Ion Transport 25.4 Metabolic Role of 2,3-Diphosphoglycerate 25.5 The Role of Glutathione and NADPH 25.6 Genetic Abnormalities: Enzyme Deficiencies Chapter 26 Blood: Blood Clotting 26.1 Introduction 26.2 Physiological Events in Blood Clotting 26.3 Platelet Adhesion and Aggregation 26.4 Roles of Prostaglandins, Endoperoxides, Prostacyclins and Thromboxanes in Platelet Aggregation 26.5 Summary of Biochemical Events in the Clotting Process 26.6 The Intrinsic Pathway 26.7 The Extrinsic Pathway 26.8 The Common Pathway of Blood Clotting 26.9 Interactions of Platelets and Plasma Factors in the Clotting Process 26.10 Fibrinolysis 26.11 Genetic Defects and Abnormalities of Blood Clotting Chapter 27 Blood: Catabolism of Haemoglobin 27.1 Role of the Reticuloendothelial System 27.2 Mechanisms of Bile Pigment Formation 27.3 Bilirubin Transport 27.4 Conjugation of Bilirubin: Role of the Liver 27.5 Excretion of Bile Pigments and Bacterial Metabolism 27.6 Development of Conjugating Enzymes 27.7 Inherited Defects of Conjugation 27.8 Hyperbilirubinaemias: Causes and Consequences Chapter 28 Blood: Iron and Iron Metabolism 28.1 Introduction 28.2 Iron Balance 28.3 Daily Iron Losses 28.4 Iron Intake and Dietary Iron 28.5 Factors Affecting Iron Absorption 28.6 the Mechanism and Control of Iron Absorption 28.7 Iron Transport: Transferrin 28.8 Iron Storage: Ferritin and Haemosiderin 28.9 Iron Kinetics 28.10 Valency of Iron During Metabolism 28.11 Iron Pathology Chapter 29 Functions of the Liver 29.1 Structure of the Liver 29.2 Metabolic Roles of the Liver: General Considerations 29.3 Role of the Liver in Carbohydrate Metabolism 29.4 Role of the Liver in Fat Metabolism 29.5 The Role of the Liver in Amino Acid Metabolism 29.6 The Role of the Liver in Protein Synthesis 29.7 The Role of the Liver in Storage 29.8 The Role of the Liver in Providing Digestive Secretions 29.9 The Excretory Role of the Liver in Synthesizing or Processing Metabolites for Excretion Chapter 30 the Kidney 30.1 Major Functions of the Kidney 30.2 the Structure of the Kidney 30.3 Mechanism of Action 30.4 Composition of the Urine 30.5 Major Metabolic Processes in the Kidney 30.6 Energy Provision in the Kidney 30.7 Water Absorption 30.8 Absorption of Electrolytes 30.9 Absorption of Glucose 30.10 Absorption of Amino Acids 30.11 Regulation of pH Chapter 31 Muscle 31.1 Microscopic Structure of Muscle 31.2 The Proteins of Muscle 31.3 Assembly of Proteins Into Filaments 31.4 Models of Muscle Contraction 31.5 Energy for Contraction 31.6 The Role of Calcium in Muscle Contraction Chapter 32 Bone and Collagen: Calcification 32.1 Bone Structure 32.2 Bone Mineral 32.3 Precipitation of Calcium Phosphate 32.4 Collagen 32.5 Biosynthesis of Collagen and the Role of Ascorbic Acid (Vitamin C) 32.6 Calcification of Bone 32.7 Resorption of Bone Chapter 33 The Brain and the Central Nervous System 33.1 Excitation and Conduction 33.2 Chemical Transmission and Transmitters 33.3 Amino Acid Transmitters 33.4 Myelin 33.5 Metabolism in the BrainPart 4 Environmental Hazards—Detoxication Chapter 34 Toxicology: General Aspects 34.1 Biochemical Damage Caused by Toxic Substances Chapter 35 Toxic Metals 35.1 Metal Complexes and Chelates 35.2 Protein Complexes 35.3 Copper 35.4 Toxicity of Mercury 35.5 Toxicity of Lead 35.6 Radionuclides 35.7 Removal of Toxic Metals: Chelation Therapy Chapter 36 Metabolism of Xenobiotics: Xenobiochemistry 36.1 Origins of Xenobiotics and Mode of Entry into the Body 36.2 General Properties of Xenobiotic Metabolites 36.3 Role of the Liver in Xenobiotic Metabolism 36.4 Phase I and Phase II Reactions 36.5 Conjugation Reactions of Xenobiotics 36.6 Reduction in Xenobiotic Metabolism 36.7 Hydrolysis of Xenobiotics 36.8 Oxidative Metabolism of Xenobiotics 36.9 Induction of Oxidative Xenobiotic Metabolism Chapter 37 Alcohol: Effects On Metabolism 37.1 Metabolism of Ethanol 37.2 Hypoglycaemic Effects of Alcohol 37.3 Effects of Alcohol on Plasma Lipids Chapter 38 Chemical Carcinogenesis 38.1 Introduction: What is Cancer? 38.2 Cancer-Causing Agents 38.3 Chemical Nature of Carcinogens—Their Occurrence in the Environment and Their Origins 38.4 How Do Carcinogens Gain Access to the Body? 38.5 Methods of Testing for Carcinogens 38.6 Factors Affecting the Carcinogenicity of Chemicals 38.7 Multistage Concept of Carcinogenesis 38.8 Metabolism of Carcinogens 38.9 Formation of Electrophilic Reagents 38.10 Site of DNA Attack 38.11 Induction of Enzyme Systems Involved in Oxidative Metabolism of CarcinogensPart 5 Biochemical Basis of Diagnosis—Disease and Its Treatment Chapter 39 Biochemical Diagnosis 39.1 Principles of Methods Used 39.2 Typical Enzymes Determined in Plasma 39.3 Distribution of Enzymes in Tissues and Serum Patterns 39.4 Isoenzymes 39.5 Examples of the Use of Measurements of Serum Enzyme in Diagnosis Chapter 40 An Example of Metabolic Disturbance: Obesity 40.1 Introduction 40.2 Measurement of Obesity 40.3 Relation of Water Loss to Obesity 40.4 The Fundamental Causes of Obesity 40.5 Regulation of Food Intake 40.6 The Adipocytes in Obesity 40.7 The Biochemical Changes Observed in Obesity 40.8 the Role of Thermogenesis in Obesity Chapter 41 Biochemical Genetics: Inborn Errors of Metabolism 41.1 Introduction 41.2 General Defects in Metabolic Processes 41.3 Clinical Manifestations of Metabolic Errors 41.4 Therapeutics 41.5 Typical Metabolic Disorders 41.6 Genetic Defects of Blood Proteins 41.7 Carbohydrate Metabolism 41.8 Defects of Amino Acid Metabolism 41.9 Lipid Metabolism 41.10 Purine/Pyrimidine Metabolism Chapter 42 Immunology 42.1 Introduction 42.2 Antigens and Antibodies 42.3 Antibody Structure: The Immunoglobulins 42.4 Antibody Synthesis: Roles of Macrophages and Lymphocytes 42.5 Control of Antibody Synthesis: Antibody Diversity 42.6 Complement 42.7 Immunity to Infection 42.8 Allergy, Autoimmune Diseases and Transplantation Chapter 43 Principles of Chemotherapy 43.1 Historical Background 43.2 Origins of New Drugs 43.3 Why are Chemotherapeutic Drugs Effective? 43.4 Relation of Chemical Structure to Chemotherapeutic Activity 43.5 Summary of Mode of Action of Chemotherapeutic Drugs 43.6 Problems in Cancer Therapy—Multiple Drug Therapy and Effect of Drugs On Cell CycleAppendices Appendix 1 Commonly Occurring Mono- and Disaccharides Appendix 2 Polysaccharides—Starch and Glycogen Appendix 3 Mucopolysaccharides—Proteoglycans Appendix 4 Naturally Occurring Α-Amino Acids Appendix 5 Lipid Chemistry and Classification Appendix 6 Phospholipids Appendix 7 Unsaturated Fatty Acids and Their Metabolism Appendix 8 Structure of the Steroids and Major Inter-Relationships Appendix 9 Purine and Pyrimidine Bases Appendix 10 Nucleosides—Nucleotides Appendix 11 Nucleic Acid Structure Appendix 12 Classification and Numbering of Enzymes Appendix 13a Enzyme Kinetics and Enzyme Inhibition Appendix 13b Example of the Mechanism of Action of an Enzyme Appendix 14 Glycolysis—Outline of Stages Appendix 15 Glycolysis Appendix 16 Pentose Phosphate Pathway—Outline of Stages Appendix 17 Citric Acid Cycle—ATP Formation Appendix 18 Citric Acid Cycle—Structures of Intermediates Appendix 19 Citric Acid Cycle—Links with Amino Acid Metabolism Appendix 20 ß-Oxidation of Fatty Acids Appendix 21 The Electron Transport Chain Appendix 22 Steroid Synthesis: Biosynthesis of Cholesterol Appendix 23 Purine Metabolism Appendix 24 Summary of Amino Acid Metabolism Appendix 25 Ornithine Cycle—Synthesis of Urea Appendix 26 Synthesis of DNA Appendix 27 Replication of DNA: Formation of Okazaki Fragments Appendix 28 Metabolic Compartmentation of Protein Synthesis Appendix 29 The Genetic Code Appendix 30 The Genetic Code—Relationships of Amino Acid Structure to Coding Symbol Appendix 31 Transfer RNAs Appendix 32 Protein SynthesisFurther ReadingIndex