Wills' Biochemical Basis of Medicine

Preface to Second EditionPreface to First EditionAcknowledgmentsPart 1 Biochemistry of the Cell and Its Metabolism Chapter 1 Ultrastructure 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 Roles of Subcellular Organelles: Lysosomes 3.1 Introduction 3.2 Origin of Lysosomal Enzymes 3.3 The Nature of the Lysosomal Enzymes 3.4 Investigation Methods and Properties of Lysosomal Enzymes 3.5 Transport Across the Lysosomal Membrane 3.6 The Life Cycle of the Lysosome 3.7 Functions of Lysosomes in the Tissues 3.8 Lysosomes in Pathological Conditions Chapter 4 Roles 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 Roles 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 the Biochemistry of Mitochondria 6.6 Relation of Mitochondrial Structure to Enzyme Activity and Function 6.7 Replication of Mitochondria Chapter 7 Roles of Subcellular Organelles: Inter-Relationships of the Mitochondria and Cytosol 7.1 Introduction 7.2 Membranes of the Mitochondria 7.3 Mitochondrial Transport Systems 7.4 Classification of Carrier Types 7.5 Classification of Carriers 7.6 Mode of Action of Typical Carriers 7.7 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 83 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 Ribosomes Further Reading to Part 1Part 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 Eats 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 Β Group 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 Roles of Metal Ions 15.6 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 Bacterial 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 17.3 Structural Relationships of the Hypothalamus and Pituitary Gland 17.4 The Hypothalamus - Anterior Pituitary - Target Organ Relationships 17.5 Biosynthesis of Peptide Hormones 17.6 Hormones of the Hypothalamus 17.7 Hormones of the Anterior Pituitary (Adenohypophysis) 17.8 Hormones of the Posterior Pituitary (Neurohypophysis) 17.9 Hormones of the Pancreas 17.10 The Thyroid and Parathyroid Glands 17.11 The Adrenal Medulla 17.12 Steroidogenic Organs 17.13 Diseases of Steroid Hormone Production 17.14 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 State 18.4 Tissue Response to Increased Plasma Insulin and Glucose Concentrations 18.5 The Role of Glucagon 18.6 Carbohydrate Metabolism in the Fetus and Newborn 18.7 Metabolism of Fructose and Galactose 18.8 Circulating Glucose under Stress Conditions Chapter 19 Plasma Lipids and Their Regulation 19.1 Introduction 19.2 Classification of Plasma Lipids 19.3 Lipid Transport in the Fed State 19.4 Lipid Transport in the Fasting State 19.5 Fatty Livers 19.6 Interactions and Interchange between Lipoproteins 19.7 Hyperlipoproteinaemias 19.8 Factors Leading to Raised Plasma Lipid Levels Chapter 20 Plasma Amino Acids and Utilization of Amino Acids by the Tissues 20.1 Introduction 20.2 How Does Man Utilize Amino Acids? 20.3 The Effect of a Protein Meal on Plasma Amino Acid Concentrations 20.4 The Utilization of Branched-Chain Amino Acids in Muscle and Formation of Alanine 20.5 The Induction of Amino Acid Catabolizing Enzymes 20.6 Amino Acid Imbalance 20.7 Hormonal Regulation of Plasma Amino Acids Chapter 21 Plasma Electrolytes 21.1 Introduction 21.2 Electrolyte Composition of Normal Plasma 21.3 Water Components of the Body 21.4 The Osmolarity of the Fluid Compartment and Its Regulation 21.5 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-Dihy Droxy-Vi Tamin-D3 22.7 Mode of Action of 1,25-Dihy Droxy-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 Introduction 23.2 Energy Storage 23.3 Phases of Starvation 23.4 Interprandial Phase 23.5 Postabsorptive Phase (Overnight Fast) 23.6 Prolonged Starvation 23.7 Clinical Aspects of Starvation - Anorexia Nervosa Further Reading to Part 2Part 3 Specialized Metabolism of Tissues Chapter 24 Blood: Erythropoiesis-Role of Folate and Vitamin Β12 24.1 Normal Erythropoiesis and Site of Formation of Abnormal Cells in Conditions of Folate and Vitamin B12 Deficiencies 24.2 Macrocytic Anemias 24.3 Causes of Folate Deficiency 24.4 Absorption and Distribution of Folate 24.5 Causes of Vitamin B12 Deficiency 24.6 Absorption and Distribution 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 Β12 24.10 Metabolic Inter-Relationships of Folate and Vitamin B12 and the 'Methyl Trap' 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 Phosphate Pathway 25.3 Utilization of ATP in Ion Transport 25.4 The 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, Prostacyclin 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 Mechanism 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 Hemosiderin 28.9 Iron Kinetics 28.10 Valency of Iron during Metabolism 28.11 Iron Pathology Chapter 29 Functions of the Liver 29.1 Introduction 29.2 Structure of the Liver 29.3 Metabolic Roles of the Liver: General Considerations 29.4 Role of the Liver in Carbohydrate Metabolism 29.5 Role of the Liver in Fat Metabolism 29.6 The Role of the Liver in Amino Acid Metabolism 29.7 The Role of the Liver in Protein Synthesis 29.8 The Role of the Liver in Storage 29.9 The Role of the Liver in Providing Digestive Secretions 29.10 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 The Glomeruler Capillary Basement Membrane 30.5 Composition of the Urine 30.6 Major Biochemical Processes in the Kidney 30.7 Energy Provision in the Kidney 30.8 Water Absorption 30.9 Absorption of Electrolytes 30.10 Absorption of Glucose 30.11 Absorption of Amino Acids 30.12 Regulation of pH Chapter 31 Muscle 31.1 Introduction 31.2 Microscopic Structure of Muscle 31.3 The Proteins of Muscle 31.4 Assembly of Proteins into Filaments 31.5 Models of Muscle Contraction 31.6 Energy for Contraction 31.7 The Role of Calcium in Muscle Contraction Chapter 32 Bone and Collagen: Calcification 32.1 Introduction 32.2 Bone Structure 32.3 Bone Mineral 32.4 Precipitation of Calcium Phosphate 32.5 Collagen 32.6 Biosynthesis of Collagen and the Role of Ascorbic Acid (Vitamin C) 32.7 Calcification of Bone 32.8 Resorption of Bone 32.9 Bone Repair Chapter 33 The Brain 33.1 Introduction 33.2 The Cell Types of the Brain 33.3 The Synapse 33.4 Excitation and Conduction 33.5 Chemical Transmission and Transmitters 33.6 Myelin 33.7 Metabolism in the Brain Chapter 34 The Eye 34.1 Introduction 34.2 The Cornea 34.3 The Lens 34.4 The RetinaPart 4 Environmental Hazards - Detoxication Chapter 35 Toxicology: General Aspects 35.1 Introduction 35.2 Biochemical Damage Caused by Toxic Substances Chapter 36 Toxic Metals 36.1 Introduction 36.2 Metal Complexes and Chelates 36.3 Protein Complexes 36.4 Copper 36.5 Toxicity of Mercury 36.6 Toxicity of Lead 36.7 Radionuclides 36.8 Removal of Toxic Metals: Chelation Therapy Chapter 37 Metabolism of Xenobiotics: Xenobiochemistry 37.1 Introduction 37.2 Origins of Xenobiotics and Mode of Entry into the Body 37.3 General Properties of Xenobiotic Metabolites 37.4 Role of the Liver in Xenobiotic Metabolism 37.5 Phase I and Phase II Reactions 37.6 Conjugation Reactions of Xenobiotics 37.7 Reduction in Xenobiotic Metabolism 37.8 Hydrolysis of Xenobiotics 37.9 Oxidative Metabolism of Xenobiotics 37.10 Induction of the Oxidative Metabolism of Xenobiotics and Intermediary Metabolites Chapter 38 Alcohol: Effects on Metabolism 38.1 Introduction 38.2 Metabolism of Ethanol 38.3 Hypoglycaemic Effects of Alcohol 38.4 Effects of Alcohol on Plasma Lipids 38.5 Effects of Alcohol on Vitamin Requirements Chapter 39 Carcinogenesis 39.1 Introduction: What is Cancer? 39.2 Cancer-Causing Agents 39.3 Chemical Nature of Many Carcinogens - Their Occurrence in the Environment and Their Origins 39.4 How do Chemical Carcinogens Gain Access to the Body? 39.5 Methods of Testing for Chemical Carcinogens 39.6 Factors Affecting the Carcinogenicity of Chemicals 39.7 Multistage Concept of Carcinogenesis 39.8 Metabolism of Carcinogens 39.9 Formation of Electrophilic Reagents 39.10 Site of DNA Attack 39.11 Induction of Enzyme Systems Involved in Oxidative Metabolism of Carcinogens 39.12 OncogenesPart 5 Biochemical Basis of Diagnosis-Disease and Its Treatment Chapter 40 Biochemical Diagnosis 40.1 Introduction 40.2 Principles of Methods Used 40.3 Typical Enzymes Determined in the Serum 40.4 Distribution of Enzymes in Tissues and Serum Patterns 40.5 Isoenzymes 40.6 Examples of the Use of Measurements of Serum Enzymes in Diagnosis Chapter 41 An Example of Metabolic Disturbance: Obesity 41.1 Introduction 41.2 Measurement of Obesity 41.3 Relation of Water Loss to Obesity 41.4 The Fundamental Causes of Obesity 41.5 Regulation of Food Intake 41.6 The Adipocytes in Obesity 41.7 The Biochemical Changes Observed in Obesity 41.8 The Role of Thermogenesis in Obesity Chapter 42 Biochemical Genetics: Inborn Errors of Metabolism 42.1 Introduction 42.2 The Nature of the Genetic Defects 42.3 Prenatal Diagnosis 42.4 Clinical Manifestations of Metabolic Errors 42.5 Therapeutics 42.6 Typical Metabolic Disorders 42.7 Genetic Defects of Blood Proteins 42.8 Carbohydrate Metabolism 42.9 Defects of Amino Acid Metabolism 42.10 Lipid Metabolism 42.11 Purine/Pyrimidine Metabolism Chapter 43 Principles of Chemotherapy 43.1 Introduction 43.2 Historical Background 43.3 Origins of New Drugs 43.4 Why are Chemotherapeutic Drugs Effective? 43.5 Relation of Chemical Structure to Chemotherapeutic Activity 43.6 Summary of Mode of Action of Chemotherapeutic Drugs 43.7 Problems in Cancer Therapy - Multiple Drug Therapy and Effect of Drugs on Cell Cycle Further Reading to Part 5Appendix 1 Commonly Occurring Mono- and DisaccharidesAppendix 2 Polysaccharides - Starch and GlycogenAppendix 3 Glycosaminoglycans (Mucopolysaccharides) - ProteoglycansAppendix 4 Naturally Occurring α-Amino AcidsAppendix 5 Lipid Chemistry and ClassificationAppendix 6 PhospholipidsAppendix 7 Purine and Pyrimidine BasesAppendix 8 Nucleosides - NucleotidesAppendix 9 GlycolysisAppendix 10 Pentose Phosphate Pathway - Outline of StagesAppendix 11 Citric Acid CycleAppendix 12 ß-Oxidation of Fatty Acids in MitochondriaAppendix 13 Biosynthesis of CholesterolAppendix 14 Summary of Amino Acid MetabolismAppendix 15 Ornithine Cycle - Synthesis of UreaAppendix 16 The Genetic CodeAppendix 17 Transfer RNAsAppendix 18 Steps in Eukaryotic Protein SynthesisIndex