Wills' Biochemical Basis of Medicine

Wills' Biochemical Basis of Medicine, Second Edition provides a basic understanding of the structure and metabolic processes in the context in which they occur in the cell or in the tissues. This book provides groundwork of academic biochemistry and demonstrations of the application of biochemistry to medicine. Organized into five parts encompassing 43 chapters, this edition begins with an overview of the biochemistry of the subcellular organelles. This text then examines the functions of the nucleus, mitochondria, and the endoplasmic reticulum. Other chapters consider the biochemistry of the hormones and the regulation of the metabolic fuels. This book discusses as well the biochemistry of environmental hazards and examines the treatment of viral carcinogenesis. The final chapter deals with the results of the application of recombinant DNA technology to the diagnosis of genetic disorder. This book is a valuable resource for biochemists, biologists, physicians, clinical researchers, and medical students.

Preface to Second Edition

Preface to First Edition

Acknowledgments

Part 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 1

Part 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 2

Part 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 Retina

Part 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 Oncogenes

Part 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 5

Appendix 1 Commonly Occurring Mono- and Disaccharides

Appendix 2 Polysaccharides - Starch and Glycogen

Appendix 3 Glycosaminoglycans (Mucopolysaccharides) - Proteoglycans

Appendix 4 Naturally Occurring α-Amino Acids

Appendix 5 Lipid Chemistry and Classification

Appendix 6 Phospholipids

Appendix 7 Purine and Pyrimidine Bases

Appendix 8 Nucleosides - Nucleotides

Appendix 9 Glycolysis

Appendix 10 Pentose Phosphate Pathway - Outline of Stages

Appendix 11 Citric Acid Cycle

Appendix 12 ß-Oxidation of Fatty Acids in Mitochondria

Appendix 13 Biosynthesis of Cholesterol

Appendix 14 Summary of Amino Acid Metabolism

Appendix 15 Ornithine Cycle - Synthesis of Urea

Appendix 16 The Genetic Code

Appendix 17 Transfer RNAs

Appendix 18 Steps in Eukaryotic Protein Synthesis

Index