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Biochemistry

Biochemistry

U Satyanarayana

(2014)

Additional Information

Book Details

Abstract

This textbook ‘Biochemistry’ has become one of the most preferred text books (in India and many other countries) for the students as well as teachers in medical, biological and other allied sciences. The book has undergone three editions, several reprints, and revised reprints in a span of 13 years.

There are many biochemistry textbooks in the market. Some of them are purely basic while others are applied, and there are very few books which cover both these aspects together. For this reason, the students learning biochemistry in their undergraduate courses have to depend on multiple books to acquire a sound knowledge of the subject.

This book, ‘Biochemistry’ is unique with a simultaneous and equal emphasis on basic and applied aspects of biochemistry. This textbook offers an integration of medical and pure sciences, comprehensively written to meet the curriculum requirements of undergraduate courses in medical, dental, pharmacy, life-sciences and other categories (agriculture, veterinary, etc.).

This book is designed to develop in students a sustained interest and enthusiasm to learn and develop the concepts in biochemistry in a logical and stepwise manner. It incorporates a variety of pedagogic aids, besides colour illustrations to help the students understand the subject quickly and to the maximum. The summary and biomedical/clinical concepts are intended for a rapid absorption and assimilation of the facts and concepts in biochemistry. The self-assessment exercises will stimulate the students to think rather than merely learn the subject. In addition, these exercises (essays, short notes, fill in the blanks, multiple choice questions) set at different difficulty levels, will cater to the needs of all the categories of learners.

New to This Edition

  • The book offers an integration of medical and pure sciences, and is comprehensively written, revised and updated to meet the curriculum requirements of Medical, Pharmacy, Dental, Veterinary, Biotechnology, Agricultural Sciences, Life Sciences, and others studying Biochemistry as one of the subjects.
  • It is the first text book on Biochemistry in English with multi-colour illustrations by an author from Asia. The use of multicolours is for a clearer understanding of the complicated biochemical reactions.
  • It is written in a lucid style with the subject being presented as an engaging story growing from elementary information to the most recent advances, and with theoretical discussions being supplemented with illustrations, flowcharts, and tables for easy understanding of Biochemistry.
  • It has each chapter beginning with a four-line verse followed by the text, biomedical concepts, a summary, and self-assessment exercises. The lively illustrations and text with appropriate headings and sub-headings in bold type faces facilitate reading path clarity and quick recall.

  • It provides the most recent and essential information on Molecular Biology and Biotechnology, Diabetes, Cancer, Free Radicals, Free radicals and Antioxidants, Prostaglandins, etc.
  • It describes a wide variety of case studies and biochemical correlations and several newer biomedical aspects- Metabolic syndrome, Therapeutic diets, Atkins diet, Trans fatty acids, Epigenetics, Nutrigenomics, Recombinant ribozymes, Membrane transport disorders, Pleural fluid etc.
  • It contains the basics (Bioorganic and Biophysical Chemistry, Tools of Biochemistry, Immunology, and Genetics) for beginners to learn easily Biochemistry, origins of biochemical words, confusables in Biochemistry, principles of Practical Biochemistry, and Clinical Biochemistry Laboratory.

Table of Contents

Section Title Page Action Price
Cover Cover
Front matter i
Copyright iv
Preface to the Fourth Edition v
Preface to the First Edition vi
Acknowledgements vii
Scope of Biochemistry viii
Contents ix
Section I - Chemical Constituents of Life 1
Chapter 1 - Biomolecules and the Cell 3
Carbon—a unique element of life 3
Chemical molecules of life 3
Complex biomolecules 3
Structural heirarchy of an organism 3
Chemical composition of man 4
The cell 4
Prokaryotic and eukaryotic cells 4
Eukaryotic cell 4
Nucleus 5
Mitochondria 6
Endoplasmic reticulum 6
Golgi apparatus 6
Lysosomes 7
Peroxisomes 7
Cytosol and cytoskeleton 7
Integration of cellular functions 7
Chapter 2 - Carbohydrates 9
Functions of carbohydrates 9
Classification of carbohydrates 9
Monosaccharides 10
Aldoses 10
Ketoses 10
Oligosaccharides 10
Polysaccharides 10
Monosaccharides—structural aspects 10
Glyceraldehyde—the reference carbohydrate 10
D- and L-isomers 12
Optical activity of sugars 12
Configuration of D-aldoses 12
Configuration of D-ketoses 12
Epimers 12
Enantiomers 13
Structure of glucose 13
Pyranose and furanose structures 14
Anomers—mutarotation 14
Mutarotation 14
Mutarotation of fructose 15
Reactions of monosaccharides 15
Tautomerization or enolization 15
Reducing properties 16
Oxidation 16
Reduction 16
Dehydration 17
Bial's test 17
Mucic acid test 17
Osazone formation 17
Formation of esters 17
Glycosides 17
Naming of glycosidic bond 18
Physiologically important glycosides 18
Derivatives of monosaccharides 18
Disaccharides 18
Maltose 18
Sucrose 19
Inversion of sucrose 19
Lactose 19
Lactulose 20
Polysaccharides 20
Homopolysaccharides 20
Starch 20
Dextrins 21
Dextrans 21
Inulin 21
Glycogen 21
Cellulose 22
Chitin 22
Heteropolysaccharides 22
Mucopolysaccharides 22
Hyaluronic acid 23
Chondroitin sulfates 23
Heparin 23
Dermatan sulfate 23
Keratan sulfate 24
Agar and pectins 24
Glycoproteins 24
Blood group substances 25
Self-assessment excercises 26
Chapter 3 - Lipids 28
Classification of lipids 28
Neutral lipids : 29
Functions of lipids 29
Fatty acids 29
Occurrence 29
Even and odd carbon fatty acids 29
Saturated and unsaturated fatty acids 29
Nomenclature of fatty acids 29
Numbering of carbon atoms 30
Length of hydrocarbon chain of fatty acids 30
Shorthand representation of fatty acids 30
Essential fatty acids 31
Biochemical basis for essentiality 31
Functions of EFA 31
Deficiency of EFA 31
Isomerism in unsaturated fatty acids 31
Hydroxy fatty acids 31
Cyclic fatty acids 31
Eicosanoids 32
Triacylglycerols 32
Fats as stored fuel 32
Fats primarily occur in adipose tissue 32
Structures of acylglycerols 32
Stereospecific numbering of glycerol 32
Properties of triacylglycerols 33
Antioxidants 33
Tests to check purity of fats and oils 33
Iodine number 33
Saponification number 33
Reichert-Meissl (RM) number 34
Acid number 34
Phospholipids 34
Glycerophospholipids 34
Sphingomyelins 34
Functions of phospholipids 34
Glycolipids 35
Gangliosides 35
Lipoproteins 35
Steroids 35
Cholesterol 36
Structure and occurrence 36
Properties and reactions 36
Functions of cholesterol 36
Ergosterol 36
Amphipathic lipids 37
Examples of amphipathic lipids 37
Orientation of amphipathic lipids 37
Membrane bilayers 38
Liposomes 38
Emulsions 38
Soaps and detergents 38
Detergents 38
Self-Assessment excercises 40
Chapter 3 40
Chapter 4 - Proteins and Amino Acids 43
Origin of the word ‘protein’ 43
Functions of proteins 43
Structural functions 43
Dynamic functions 43
Elemental composition of proteins 43
Proteins are polymers of amino acids 44
Standard amino acids 44
Amino acids 44
General structure of amino acids 44
Optical isomers of amino acids 44
Classification of amino acids 44
Heterocyclic amino acids 48
Selenocysteine – the 21st amino acid 49
Pyrrolysine – the 22nd amino acid? 49
Properties of amino acids 49
Physical properties 49
Zwitterion or dipolar ion 49
Titration of amino acids 50
Chemical properties 50
Non-standard amino acids 51
Amino acids useful as drugs 51
Structure of proteins 52
Primary structure of protein 53
Peptide bond 53
Formation of a peptide bond 53
Characteristics of peptide bonds 53
Writing of peptide structures 53
Shorthand to read peptides 54
Naming of peptides 54
Dimensions of a peptide chain 54
Determination of primary structure 54
Separation and estimation of amino acids 54
Enzymatic cleavage 55
Chemical cleavage 55
Sanger's reagent 56
Edman's reagent 56
Sequenator 56
Overlapping peptides 56
Reverse sequencing technique 56
Secondary structure of protein 56
α-Helix 56
β-Pleated sheet 57
Parallel and anti-parallel β-sheets 57
Occurrence of β-sheets 58
Other types of secondary structures 58
Tertiary structure of protein 58
Bonds of tertiary structure 58
Domains 58
Quaternary structure of protein 58
Bonds in quaternary structure 58
Importance of oligomeric proteins 58
Examples of oligomeric proteins 58
Bonds responsible for protein structure 58
Disulfide bonds 58
Examples of protein structure 59
Structure of human insulin 59
Methods to determine protein structure 59
Methods for the isolation and purification of proteins 60
Properties of proteins 60
Precipitation at pI 60
Precipitation by salting out 60
Precipitation by salts of heavy metals 60
Precipitation by anionic or alkaloid reagents 61
Precipitation by organic solvents 61
Biuret reaction 61
Denaturation 61
Agents of denaturation 62
Physical agents 62
Chemical agents 62
Characteristics of denaturation 62
Coagulation 62
Flocculation 62
Classification of proteins 63
Functional classification of proteins 63
Protein classification based on chemical nature and solubility 63
Nutritional classification of proteins 64
Biologically important peptides 64
Functions 64
Self-assessment excercises 66
Chapter 4 66
Chapter 5 - Nucleic Acids and Nucleotides 69
Brief history 69
Functions of nucleic acids 69
Components of nucleic acids 69
Nucleotides 69
Structure of nucleotides 70
Purines and pyrimidines 70
Major bases in nucleic acids 70
Tautomeric forms of purines and pyrimidines 70
Minor bases found in nucleic acids 71
Other biologically important bases 71
Purine bases of plants 71
Sugars of nucleic acids 71
Nomenclature of nucleotides 71
The binding of nucleotide components 71
Nucleoside di- and triphosphates 72
Purine, pyrimidine and nucleotide analogs 73
Structure of DNA 73
Schematic representation of polynucleotides 73
Chargaff's rule of DNA composition 73
DNA double helix 74
Conformations of DNA double helix 75
Other types of DNA structure 76
Bent DNA 76
Triple-stranded DNA 76
Four-stranded DNA 76
The size of DNA molecule —units of length 77
Denaturation of DNA strands 78
Organization of DNA in the cell 78
Organization of prokaryotic DNA 78
Organization of eukaryotic DNA 78
Structure of RNA 78
Types of RNA 78
Messenger RNA (mRNA) 80
Transfer RNA (tRNA) 80
Base pairs in tRNA 81
Ribosomal RNA (rRNA) 81
Other RNAs 81
Catalytic RNAs—ribozymes 81
Recombinant ribozymes (rribozymes) 81
Self-assessment excercises 83
Chapter 5 83
Chapter 6 - Enzymes 85
Historical background 85
Nomenclature and classification 86
Chemical nature and properties of enzymes 87
Genetic engineering and modified enzymes 87
Hybrid enzymes 87
Site-directed mutagenesis 87
Factors affecting enzyme activity 88
1. Concentration of enzyme 88
2. Concentration of substrate 88
Enzyme kinetics and Km value 88
Lineweaver-Burk double reciprocal plot 89
Enzyme reactions with two or more substrates 89
3. Effect of temperature 90
Clinical significance 90
4. Effect of pH 90
5. Effect of product concentration 90
6. Effect of activators 91
7. Effect of time 91
8. Effect of light and radiation 91
Active site 91
Salient features of active site 91
Enzyme inhibition 92
1. Reversible inhibition 92
Antimetabolites 93
2. Irreversible inhibition 94
Suicide inhibition 95
3. Allosteric inhibition 95
Enzyme inhibition by drugs 95
Enzyme specificity 95
Coenzymes 96
Coenzymes are second substrates 96
Coenzymes from B-complex vitamins 97
Non-vitamin coenzymes 97
Nucleotide coenzymes 97
Protein coenzymes 98
Coenzymes do not decide enzyme specificity 98
Mechanism of enzyme action 98
Enzymes lower activation energy 98
Enzyme-substrate complex formation 98
Lock and key model or Fischer's template theory 98
Induced fit theory or Koshland's model 98
Substrate strain theory 99
Mechanism of enzyme catalysis 99
Thermodynamics of enzymatic reactions 100
Regulation of enzyme activity in the living system 100
1. Allosteric regulation and allosteric inhibition 100
Allosteric effectors 101
Classes of allosteric enzymes 101
Conformational changes in allosteric enzymes 101
Feedback regulation 102
2. Activation of latent enzymes 102
3. Compartmentation 103
4. Control of enzyme synthesis 104
Induction and repression 104
Examples of enzyme induction 104
Examples of repression 104
5. Enzyme degradation 104
6. Isoenzymes 104
Units of enzyme activity 104
Katal 104
International Units (IU) 104
Laboratory use of enzyme units 105
Non-protein enzymes 105
Ribozymes 105
Applications of enzymes 105
Enzymes as therapeutic agents 105
Enzymes as analytical reagents 106
Immobilized enzymes 106
Diagnostic importance of enzymes 106
1. Plasma specific or plasma functional enzymes 106
2. Non-plasma specific or plasma non-functional enzymes 106
Amylase 107
Alanine transaminase (ALT/SGPT) 107
Aspartate transaminase (AST/SGOT) 107
Alkaline phosphatase (ALP) 107
Acid phosphatase (ACP) 107
Lactate dehydrogenase (LDH) 107
Creatine kinase (CK) 107
γ-Glutamyl transpeptidase (GGT) 109
Decreased plasma enzyme activities 109
Isoenzymes 109
Explanation for the existence of isoenzymes 109
Isoenzymes of lactate dehydrogenase (LDH) 109
Structure of LDH isoenzymes 109
Significance of differential catalytic activity 110
Diagnostic importance of LDH 110
Isoenzymes of creatine phosphokinase 111
Isoenzymes of alkaline phosphatase 111
Isoenzymes of alcohol dehydrogenase 111
Enzyme pattern in diseases 111
Enzymes in myocardial infarction 111
Cardiac troponins (CT) 111
Enzymes in liver diseases 111
Enzymes in muscle diseases 111
Enzymes in cancers 112
Diagnostic importance of enzymes in other body fluids and tissues 112
Urine 113
Cerebrospinal fluid 113
Gastric juice 113
Feces 113
Liver 113
Muscle 113
Erythrocytes 113
Self-assessment excercises 114
Chapter 6 114
Chapter 7 - Vitamins 116
History and nomenclature 116
Classification of vitamins 117
Synthesis of vitamins by intestinal bacteria 117
Fat soluble vitamins—general 118
Water soluble vitamins—general 118
Vitamers 118
Individual vitamins 118
Vitamin A 118
Chemistry 118
Absorption, transport and mobilization 119
Biochemical functions 119
Vitamin A and vision 119
Rods and cones 121
Wald's visual cycle 121
Dark adaptation time 121
Bleaching of rhodopsin 121
Visual cascade and cGMP 121
Colour vision 122
Other biochemical functions of vitamin A 122
Recommended dietary allowance (RDA) 122
Dietary sources 123
Vitamin A deficiency 123
Deficiency manifestations of the eyes 123
Other deficiency manifestations 123
Effect on growth 123
Effect on reproduction 123
Effect on skin and epithelial cells 123
Hypervitaminosis A 123
Beneficial effects of β-carotene 123
Vitamin D 123
Chemistry 124
Absorption, transport and storage 124
Metabolism and biochemical functions 124
Synthesis of 1,25-DHCC 124
Regulation of the synthesis of 1,25-DHCC 124
Biochemical functions 125
Vitamin D is a hormone and not a vitamin—justification 127
Recommended dietary allowance (RDA) 127
Dietary sources 127
Deficiency symptoms 127
Renal rickets (renal osteodystrophy) 128
Hypervitaminosis D 128
Vitamin E 128
Chemistry 128
Absorption, transport and storage 128
Biochemical functions 128
Vitamin E and selenium 129
Recommended dietary allowance (RDA) 129
Dietary sources 129
Deficiency symptoms 129
Toxicity of vitamin E 129
Vitamin K 129
Chemistry 130
Absorption, transport and storage 130
Biochemical functions 130
Role of Gla in clotting 130
Recommended dietary allowance (RDA) 130
Dietary sources 131
Deficiency symptoms 131
Hypervitaminosis K 131
Antagonists of vitamin K 131
Vitamin C (Ascorbic acid) 132
Chemistry 132
Biosynthesis and metabolism 132
Biochemical functions 132
Recommended dietary allowance (RDA) 133
Section II - Physiological Biochemistry 163
Chapter 8 - Digestion and Absorption 165
Gastrointestinal tract 165
Carbohydrates 166
Digestion 166
Digestion in the mouth 166
Carbohydrates not digested in the stomach 166
Digestion in the small intestine 166
Absorption of monosaccharides 167
Mechanism of absorption 168
Oral rehydration therapy (ORT) 168
Absorption of fructose 168
Non-digestible carbohydrates 168
Abnormalities of carbohydrate digestion 169
Lactose intolerance 169
Sucrase deficiency 169
The problem of flatulence 169
Proteins 169
I. Digestion of proteins by gastric secretion 170
Hydrochloric acid 170
Pepsin 170
Rennin 170
II. Digestion of proteins by pancreatic proteases 170
Release and activation of zymogens 171
Specificity and action of pancreatic proteases 171
Action of carboxypeptidases 171
III. Digestion of proteins by small intestinal enzymes 171
Absorption of amino acids and dipeptides 171
Mechanism of amino acid absorption 172
Absorption of intact proteins and polypeptides 172
Abnormalities of protein digestion and amino acid absorption 173
Hartnup's disease (neutral amino aciduria) 173
Lipids 173
Minor digestion of lipids in the stomach 173
Emulsification of lipids in the small intestine 173
Digestion of lipids by pancreatic enzymes 174
Degradation of triacylglycerols (fat) 174
Degradation of cholesteryl esters 174
Degradation of phospholipids 174
Absorption- of lipids 174
Role of bile salts in lipid absorption 175
Mechanism of lipid absorption 176
Synthesis of lipids in the intestinal mucosal cells 176
Secretion of lipids from the intestinal mucosal cells 176
Abnormalities of lipid digestion and absorption 177
Steatorrhea 177
Cholesterol stones 178
Obesity and fat absorption 178
Nucleic acids 178
Abnormalities related to digestion and absorption 178
Peptic ulcers 178
Pancreatitis 178
Celiac disease (celiac sprue) 179
Self-assessment exercises 180
Answers to Self-assessment Exercises 180
Chapter 9 - Plasma Proteins 182
Importance of blood 182
Separation of plasma proteins 182
Electrophoresis 182
Abnormal electrophoretic pattern 182
Albumin/globulin (A/G) ratio 182
Components of plasma proteins 182
Albumin 182
Synthesis of albumin 182
Functions of albumin 182
Clinical significance of albumin 182
Globulins 182
a1-Antitrypsin 182
Clinical significance of a1-antitrypsin 182
a2-Macroglobulin 182
Haptoglobin 182
Functions of haptoglobin 182
Clinical significance of Hp 182
Ceruloplasmin 182
Transferrin 182
Acute phase proteins 182
C-reactive protein (CRP) 182
Immunoglobulins 182
ImmunoglobulinsŠbasic concepts 182
Structure of immunoglobulins 182
Constant and variable regions 182
Proteolytic cleavage of Ig 182
Classes of immunoglobulins 182
Immunoglobulin G (IgG) 182
Immunoglobulin A (IgA) 182
Immunoglobulin M (IgM) 182
Immunoglobulin D (IgD) 182
Immunoglobulin E (IgE) 182
Production of immunoglobulins by multiple genes 182
Antibody diversity 182
Multiple myeloma 182
Abnormal Ig production 182
Electrophoretic pattern 182
Bence Jones proteins 182
Blood clotting 182
Conversion of fibrinogen to fibrin 182
Conversion of prothrombin to thrombin 182
The extrinsic pathway 182
The intrinsic pathway 182
Anticoagulants 182
Fibrinolysis 182
Abnormalities in blood clotting 182
Hemophilia A (classical hemophilia) 182
Hemophilia B (Christmas disease) 182
Von Willebrand's disease 182
Self-Assessment Exercises 182
Answers to Self-assessment Exercises 182
Chapter 10 - Hemoglobin and Porphyrins 196
Hemoglobin 196
Structure of hemoglobin 196
Structure of globin 196
Structure of heme 197
Other forms of hemoglobin 197
Myoglobin 197
Functions of hemoglobin 197
Binding of O2 to hemoglobin 197
Oxygen dissociation curve 198
Cooperative binding of O2 to hemoglobin 198
Transport of O2 to the tissues 198
T and R forms of hemoglobin 198
T-form of Hb 198
R-form of Hb 198
Transport of CO2 by hemoglobin 199
Bohr effect 199
Mechanism of Bohr effect 200
Role of Cl– in oxygen transport 200
Effect of 2,3-bisphosphoglycerate on O2 affinity of Hb 200
Binding of 2,3-BPG to deoxyhemoglobin 201
Mechanism of action of 2,3-BPG 201
Clinical significance of 2,3-BPG 201
Hemoglobin derivatives 202
Methemoglobin 202
Carboxyhemoglobin (COHb) 202
Abnormal hemoglobins 202
Basic concepts of globin synthesis 202
Hemoglobinopathies 203
Sickle-cell anemia or sickle-cell hemoglobin 203
Occurrence of the disease 203
Molecular basis of HbS 203
Homozygous and heterozygous HbS 204
Abnormalities associated with HbS 204
Mechanism of sickling in sickle-cell anemia 204
Sticky patches and formation of deoxyhemoglobin fibres 204
Sickle-cell trait provides resistance to malaria 205
Diagnosis of sickle-cell anemia 206
Management of sickle-cell disease 206
Hemoglobin C disease 206
Hemoglobin D 206
Hemoglobin E 206
Thalassemias 206
Molecular basis of thalassemias 207
α-Thalassemias 207
β-Thalassemias 207
Porphyrins 208
Presentation and nomenclature of porphyrins 208
Type I porphyrins 208
Type III porphyrins 208
Porphyrins in cancer therapy 208
Biosynthesis of heme 210
Regulation of heme synthesis 210
Regulation in the liver 210
Effect of drugs on ALA synthase activity 210
Regulation in the erythroid cells 212
Porphyrias 212
I. Acute intermittent porphyria 212
II. Congenital erythropoietic porphyria 213
III. Porphyria cutanea tarda 213
IV. Hereditary coproporphyria 214
V. Variegate porphyria 214
VI. Protoporphyria 214
Acquired (toxic) porphyrias 214
Degradation of heme to bile pigments 214
Fate of globin 214
Sources of heme 214
Heme oxygenase 214
Biliverdin reductase 215
Transport of bilirubin to liver 215
Conjugation of bilirubin 216
Excretion of bilirubin into bile 216
Fate of bilirubin 216
Jaundice 216
Classification of jaundice 216
Jaundice due to genetic defects 217
Neonatal-physiologic jaundice 217
Phototherapy 218
Crigler-Najjar syndrome type I 218
Crigler-Najjar syndrome type II 218
Gilbert's disease 218
Self-assessment exercises 218
Answers to Self-assessment Exercises 218
Chapter 11 - Biological Oxidation 221
Bioenergetics 221
Free energy 221
Negative and positive ΔG 222
ΔG° is related to equilibrium constant (Keq) 222
ΔG is an additive value for pathways 222
High-energy compounds 222
Classification of high-energy compounds 223
High-energy bonds 223
ATP-the most important high-energy compound 223
ATP-ADP Cycle 223
Synthesis of ATP 224
Storage forms of high-energy phosphates 224
Biological oxidation 224
Redox potential (E0) 224
Electron transport chain 225
Mitochondria-the power houses of cell 225
Mitochondrial organization 225
Inner mitochondrial membrane 226
Mitochondrial matrix 226
Structural organization of respiratory chain 226
Components and reactions of the electron transport chain 226
I. Nicotinamide nucleotides 226
II. Flavoproteins 227
III. Iron-sulfur proteins 227
IV. Coenzyme Q 228
V. Cytochromes 228
Cytochrome a and a3 228
Oxidative phosphorylation 228
P : O Ratio 228
Sites of oxidative phosphorylation in ETC 229
Energetics of oxidative phosphorylation 229
Mechanism of oxidative phosphorylation 229
Chemical coupling hypothesis 229
Chemiosmotic hypothesis 229
Proton gradient 229
Rotary motor model for ATP generation 230
Inherited disorders of oxidative phosphorylation 231
Inhibitors of electron transport chain 232
Cyanide poisoning 232
Inhibitors of oxidative phosphorylation 232
Uncouplers 232
Physiological uncouplers 232
Significance of uncoupling 232
Ionophores 232
Other inhibitors of oxidative phosphorylation 232
Oligomycin 232
Atractyloside 233
Transport of reducing equivalents—shuttle pathways 233
I. Glycerol-phosphate shuttle 233
II. Malate-aspartate shuttle 233
Shuttle pathways and tissues 234
Enzymes involved in biological oxidation 234
Electron transport in prokaryotes 235
Self-assessment exercises 237
Chapter 11 237
Section III - Metabolisms 239
Chapter 12 - Introduction to Metabolism 241
Catabolism 241
Anabolism 241
Types of metabolic reactions 241
Methods employed to study metabolism 241
Chapter 13 - Metabolism of Carbohydrates 244
Major pathways of carbohydrate metabolism 244
Entry of glucose into cells 245
Glycolysis 245
Salient features 245
Reactions of glycolysis 246
Conversion of pyruvate to lactate—significance 248
Lactic acidosis 248
Production of ATP in glycolysis 249
Glycolysis and shuttle pathways 249
Cancer and glycolysis 249
Irreversible steps in glycolysis 250
Regulation of glycolysis 250
Role of fructose 2,6-bisphosphate in glycolysis 250
Pasteur effect 251
Crabtree effect 251
Glycolysis and dental caries 251
Rapaport-leubering cycle 251
Significance of 2,3-BPG 251
Conversion of pyruvate to acetyl CoA 252
Reactions of PDH complex 252
Arsenic poisoning 253
Regulation of PDH 253
Biochemical importance of PDH 253
Metabolic importance of pyruvate 253
Citric acid cycle 254
TCA cycle—the central metabolic pathway 254
Brief history 254
Location of TCA cycle 254
TCA cycle—an overview 254
TCA cycle—an open cycle 254
Reactions of citric acid cycle 254
Summary of TCA cycle 256
Requirement of O2 by TCA cycle 256
Energetics of citric acid cycle 256
Role of vitamins in TCA cycle 256
Inhibitors of Krebs cycle 256
Fluoroacetate – a suicide substrate 257
Regulation of citric acid cycle 257
Amphibolic nature of the citric acid cycle 257
Anaplerosis or anaplerotic reactions 257
Energetics of glucose oxidation 258
Gluconeogenesis 258
Location of gluconeogenesis 258
Importance of gluconeogenesis 259
Reactions of gluconeogenesis 259
Gluconeogenesis from amino acids 261
Gluconeogenesis from glycerol 261
Gluconeogenesis from propionate 261
Gluconeogenesis from lactate (Cori cycle) 261
Glucose-alanine cycle 262
Regulation of gluconeogenesis 262
Influence of glucagon 262
Availability of substrates 262
Acetyl CoA promotes gluconeogenesis 263
Alcohol inhibits gluconeogenesis 263
Gluconeogenesis from fat? 263
Glycogen metabolism 263
Functions of glycogen 263
Why store glycogen as a fuel reserve? 263
Glycogenesis 263
Glycogenolysis 265
Degradation of glycogen by lysosomal acid maltase 266
Regulation of glycogenesis and glycogenolysis 266
cAMP as second messenger for hormones 266
Regulation of glycogen synthesis by cAMP 267
Regulation of glycogen degradation by cAMP 267
Futile cycles 268
Glycogen storage diseases 269
von Gierke's disease (type I) 269
Hexose monophosphate shunt 270
HMP shunt—a unique multifunctional pathway 271
Location of the pathway 271
Reactions of the pathway 271
G6PD regulates HMP shunt 271
Significance of HMP shunt 274
Importance of pentoses 274
Importance of NADPH 274
Glucose 6-phosphate dehydrogenase deficiency 274
Clinical manifestations in G6PD deficiency 274
G6PD deficiency and resistance to malaria 275
Wernicke-Korsakoff syndrome 275
Uronic acid pathway 275
Effect of drugs on uronic acid pathway 275
Essential pentosuria 276
Metabolism of galactose 276
Disorders of galactose metabolism 277
Classical galactosemia 277
Diagnosis 277
Treatment 277
Galactokinase deficiency 277
Metabolism of fructose 278
Sorbitol / Polyol pathway 279
Sorbitol pathway in diabetes mellitus 279
Defects in fructose metabolism 279
High fructose consumption and the risk of atheroslerosis 279
Metabolism of amino sugars 280
Mucopolysaccharidoses 280
Glyoxylate cycle 280
Location of the cycle 281
Reactions of the cycle 281
Self-assessment Exercises 283
Chapter 13 283
Chapter 14 - Metabolism of Lipids 285
Triacylglycerols Šthe body fuel reserve 285
Why should fat be the fuel reserve of the body? 285
Other important body lipids 285
Transport of lipids 285
Plasma lipids 285
Dynamic state of body lipids 285
Mobilization of fat from adipose tissue 285
Regulation of hormone-sensitive TG-lipase 285
Fate of glycerol 285
Fate of free fatty acids 285
Triacylglycerol/fatty acid cycle 285
Fatty acid oxidation 285
Fatty acid oxidation Šstages and tissues 285
I. Fatty acid activation 285
II. Transport of acyl CoA into mitochondria 285
Inhibitor of carnitine shuttle 285
III. b-Oxidation proper 285
Oxidation of palmitoyl CoA 285
Energetics of b-oxidation 285
SIDSŠa disorder due to blockade in b-oxidation 285
Jamaican vomiting sickness 285
Oxidation of odd carbon chain fatty acids 285
Methylmalonic acidemia 285
Oxidation of unsaturated fatty acids 285
b-Oxidation of fatty acids in peroxisomes 285
a-Oxidation of fatty acids 285
-Oxidation of fatty acids 285
Oxidation of fatty acids and metabolic water 285
Ketone bodies 285
Ketogenesis 285
Utilization of ketone bodies 285
Overproduction of ketone bodies 285
Starvation 285
Ketonuria and weight loss programs 285
Diabetes mellitus 285
Regulation of ketogenesis 285
Ketogenic and antiketogenic substances 285
Ketoacidosis 285
Treatment of ketoacidosis 285
Biosynthesis of fatty acids 285
I. Production of acetyl CoA and NADPH 285
Advantages of coupled transport of acetyl CoA and NADPH 285
II. Formation of malonyl CoA 285
III. Reactions of fatty acid synthase complex 285
Summary of palmitate synthesis 285
Fatty acid synthase complex 285
Functional significance of FAS complex 285
Regulation of fatty acid synthesis 285
Acetyl CoA carboxylase 285
Hormonal influence 285
Dietary regulation 285
Availability of NADPH 285
Desaturation of fatty acid chains 285
Synthesis of long chain fatty acids from palmitate 285
Comparison between fatty acid synthesis and oxidation 285
Synthesis of triacylglycerols 285
Synthesis of glycerol 3-phosphate 285
Addition of acyl groups to form TG 285
Metabolism of phospholipids 285
Synthesis of phospholipids 285
Degradation of phospholipids 285
Role of LCAT in lecithin metabolism 285
Degradation of sphingomyelins 285
Niemann-Pick disease 285
Farber's disease 285
Metabolism of glycolipids 285
Synthesis of cerebrosides 285
Metabolic disorders of cerebrosides 285
Gaucher's disease 285
Krabbe's disease 285
Sphinogolipidoses 285
Metabolism of cholesterol 285
Functions of cholesterol 285
Cholesterol biosynthesis 285
Regulation of cholesterol synthesis 285
Degradation of cholesterol 285
I. Synthesis of bile acids 285
Enterohepatic circulation 285
Cholelithiasis 285
II. Synthesis of steroid hormones from cholesterol 285
III. Synthesis of vitamin D 285
Transport of cholesterol 285
Role of LCAT 285
Plasma cholesterolŠ biomedical importance 285
Hypercholesterolemia 285
Bad cholesterol and good cholesterol 285
Affects of lifestyles on serum cholesterol level 285
Control of hypercholesterolemia 285
Hypocholesterolemia 285
Lipoproteins 285
Structure of lipoproteins 285
Classification of lipoproteins 285
Apolipoproteins (apoproteins) 285
Metabolism of lipoproteins Ša general view 285
Role of lipoprotein lipase 285
Uptake of chylomicron remnants by liver 285
Conversion of VLDL to LDL 285
Cholesterol ester transfer protein (CETP) 285
LDL receptors and supply of cholesterol to tissues 285
Deficiency of LDL receptors 285
Metabolism of hdl 285
Role of LCAT in HDL metabolism 285
Cardioprotective function of HDL 285
Disorders of plasma lipoproteins 285
Hyperlipoproteinemias 285
Hypolipoproteinemias 285
Familial alpha-lipoprotein deficiency (Tangier disease) 285
Fatty liver 285
Endocrine factors 285
Lipotropic factors 285
Important lipotropic factors 285
Action of lipotropic factors 285
Choline deficiency and fatty liver 285
Obesity 285
Nutritional basis 285
Obesity due to virus infection 285
Body mass index (BMI) 285
Genetics, obesity and leptin 285
Obesity and adipose tissue 285
Pharmacological treatment of obesity 285
Metabolic syndrome 285
Cachexia 285
Atherosclerosis 285
Causes of atherosclerosis and CHD 285
Disorders that may cause atherosclerosis 285
Relation between HDL and CHD 285
Lipoprotein a and CHD 285
Antioxidants and atherosclerosis 285
Alcohol metabolism 285
Biochemical changes in alcoholism 285
Effects of chronic alcoholism 285
Self-assessment exercises 285
Chapter 14 285
Chapter 15 - Metabolism of Amino Acids 330
Amino acid pool 330
I. Sources of amino acid pool 331
II. Utilization of amino acids from body pool 331
Metabolism of amino acids —general aspects 332
Transamination 332
Salient features of transamination 332
Mechanism of transamination 333
Deamination 334
I. Oxidative deamination 334
Regulation of GDH activity 334
Oxidative deamination by amino acid oxidases 334
Fate of D-amino acids 335
II. Non-oxidative deamination 335
Metabolism of ammonia 335
I. Formation of ammonia 335
II. Transport and storage of NH3 335
Role of glutamine 336
III. Functions of ammonia 336
IV. Disposal of ammonia 336
V. Toxicity of ammonia 336
Hyperammonemia 336
Explanation for NH3 toxicity 336
Trapping and elimination of ammonia 337
Urea cycle 337
Overall reaction and energetics 339
Regulation of urea cycle 339
Disposal of urea 339
Integration between urea cycle and TCA cycle 339
Metabolic disorders of urea cycle 340
Blood urea—clinical importance 340
Non-protein nitrogen (NPN) 341
Metabolism of individual amino acids 341
Glycine 341
Glycine in proteins 341
Synthesis of glycine 342
Degradation of glycine 342
Synthesis of specialized products 342
Creatine and creatinine—clinical importance 344
Metabolic disorders of glycine 344
Phenylalanine and tyrosine 345
345
Conversion of phenylalanine to tyrosine 345
Degradation of tyrosine (phenylalanine) 346
Synthesis of melanin 348
Melanin—the colour pigment 348
Biosynthesis of thyroid hormones 349
Biosynthesis of catecholamines 349
Functions of catecholamines 350
Dopamine and Parkinson's disease 350
Biochemical basis 350
Treatment 350
Disorders of tyrosine (phenylalanine) metabolism 351
Phenylketonuria 351
Phenylalanine metabolism in PKU 351
Clinical/biochemical manifestations of PKU 351
Diagnosis of PKU 352
Treatment of PKU 352
Tyrosinemia type II 352
Neonatal tyrosinemia 352
Alkaptonuria (Black urine disease) 352
Enzyme defect 352
Biochemical manifestations 352
Diagnosis 352
Treatment 353
Tyrosinosis or tyrosinemia type I 353
Albinism 353
Biochemical basis 353
Clinical manifestations 353
Hypopigmentation 353
Tryptophan 354
I. Kynurenine pathway 354
NAD+ Pathway 356
Conversion of tryptophan to indole acetate 356
II. Serotonin pathway 356
Synthesis of serotonin 356
Degradation of serotonin 356
Functions of serotonin 356
Serotonin and brain 356
Effect of drugs on serotonin 356
Malignant carcinoid syndrome 356
Diagnosis 358
Melatonin 358
Functions of melatonin 358
Hartnup's disease 358
Sulfur amino acids 358
Metabolism of methionine 358
Transmethylation 359
Synthesis of S-adenosylmethionine 359
Functions of S-adenosylmethionine 359
Significance of transmethylation 360
Synthesis of cysteine 360
Homocysteine and heart attacks 360
Degradation of cysteine 361
Inborn errors of sulfur amino acid metabolism 361
Cystinosis (cystine storage disease) 361
Homocystinurias 362
Homocystinuria II 362
Homocystinuria III 362
Homocystinuria IV 362
One-carbon metabolism 363
I. Generation of one-carbon units 363
II. Utilization of one-carbon moieties 363
III. Role of methionine and B12 in one-carbon metabolism 363
Branched chain amino acids 363
Metabolic defects of branched chain amino acids 365
Enzyme defect 365
Biochemical complications and symptoms : 365
Diagnosis and treatment 365
Histidine, proline and arginine 366
Histidine 366
Histidinemia 366
Proline 366
Hyperprolinemia type I 366
Arginine 366
Nitric oxide (NO) 366
Functions of NO 367
Mechanism of action 368
Agmatine 368
Lysine 368
Synthesis of carnitine 368
Biochemical importance of carnitine 368
Glutamate and glutamine 369
Functions of GABA 370
Vitamin B6 deficiency and GABA 370
Glutamine 370
Aspartate and asparagine 370
Alanine 371
Serine 371
Threonine 372
Fate of carbon skeleton of amino acids 372
Biosynthesis of non-essential amino acids 374
Inborn errors of amino acid metabolism—a summary 374
Amino aciduria 374
Amino acids as neurotransmitters 374
Biogenic amines 374
Polyamines 374
Biosynthesis 374
Degradation of polyamines 374
Functions of polyamines 374
Clinical importance and polyamines 376
Self-assessment exercises 378
Answers to Self-assessment Exercises 378
Chapter 16 - Integration of Metabolism 380
Energy demand and supply 380
Integration of major metabolic pathways of energy metabolism 380
Regulation of metabolic pathways 382
Organ specialization and metabolic integration 382
Liver 382
Adipose tissue 382
Skeletal muscle 382
Brain 382
Metabolism in starvation 383
Liver in starvation 383
Adipose tissue in starvation 384
Skeletal muscle in starvation 385
Brain in starvation 385
Chapter 17 - Metabolism of Nucleotides 387
Biosynthesis of purine ribonucleotides 387
Inhibitors of purine synthesis 390
Synthesis of AMP and GMP from IMP 390
Formation of purine nucleoside diphosphates and triphosphates 391
Salvage pathway for purines 391
Regulation of purine nucleotide biosynthesis 392
Conversion of ribonucleotides to deoxyribonucleotides 392
Supply of reducing equivalents 392
Regulation of deoxyribonucleotide synthesis 392
Degradation of purine nucleotides 392
Disorders of purine metabolism 394
Hyperuricemia and gout 394
Uric acid pool in gout 396
Treatment of gout 396
Pseudogout 396
Lesch-Nyhan syndrome 396
Immunodeficiency diseases associated with purine metabolism 397
Hypouricemia 397
Biosynthesis of pyrimidine ribonucleotides 397
Regulation of pyrimidine synthesis 397
Degradation of pyrimidine nucleotides 399
Salvage pathway 399
Disorders of pyrimidine metabolism 399
Orotic aciduria 399
Reye's syndrome 399
Biosynthesis of nucleotide coenzymes 399
Self-assessment exercises 401
Answers to Self-assessment Exercises 401
Chapter 18 - Mineral Metabolism 403
General functions 403
Classification 403
Calcium 404
Biochemical functions 404
Dietary requirements 406
Sources 406
Absorption 406
Factors promoting Ca absorption 406
Factors inhibiting Ca absorption 406
Plasma calcium 406
Factors regulating plasma Ca level 407
Calcitriol 407
Parathyroid hormone 407
Mechanism of action of PTH 407
Action on the bone 407
Action on the kidney 407
Action on the intestine 407
Calcitonin 407
Importance of Ca : P ratio 408
Excretion of calcium 408
Calcium in the teeth 408
Disease states 408
Hypercalcemia 408
Hypocalcemia 408
Treatment 408
Rickets 408
Renal rickets 408
Osteoporosis 409
Occurrence 409
Etiology 409
Treatment 409
Osteopetrosis (marble bone disease) 409
Phosphorus 409
Biochemical functions 409
Dietary requirements 409
Sources 409
Absorption 409
Serum phosphate 410
Excretion 410
Section IV - Clinical Biochemistry and Nutrition 425
Chapter 19 - Hormones 427
Classification of hormones 427
I. Based on the chemical nature 427
II. Based on the mechanism of action 427
Mechanism of action of group I hormones 428
Mechanism of action of group II hormones 428
cAMPŠThe second messenger 430
Adenylate cyclase system 430
Action of cAMPŠa general view 430
Dephosphorylation of proteins 430
Degradation of cAMP 431
Hypothalamic and pituitary hormones 431
Hypothalamic hormones 431
Anterior pituitary hormones 432
I. The growth hormone-prolactin group 433
Growth hormone (GH) 433
Regulation of GH release 433
Biochemical functions of GH 433
Abnormalities of GH production 434
Deficiency of GH 434
Overproduction of GH 434
Prolactin 434
Biochemical functions of PRL 434
II. The glycoprotein hormones 434
Regulation of TSH production 434
Functions of TSH 434
Gonadotropins 435
III. The pro-opiomelanocortin (POMC) peptide family 435
Products of POMC 435
Regulation of ACTH production 435
Overproduction of ACTH 436
Endorphins and enkephalins 436
Synthesis 436
Biochemical actions 436
Posterior pituitary hormones 437
Oxytocin 437
Chapter 20 - Organ Function Tests 453
Liver function tests 453
Major functions of liver 453
Causes of liver damage 454
Tests to assess liver function 454
Markers of liver function 454
Bilirubin 454
Serum bilirubin 454
Icterus index 454
van den Bergh reaction 455
Mechanism of the reaction 455
Direct and indirect reactions 455
van den Bergh reaction and jaundice 455
Bilirubin in urine 455
Bromosulphthalein (BSP) test 455
Serum enzymes derived from liver 455
Transaminases or aminotransferases 455
Alkaline phosphatase 456
γ-Glutamyl transpeptidase 456
5′-Nucleotidase 456
Other enzymes 456
Enzyme combinations 456
Jaundice 456
Hemolytic jaundice 457
Obstructive jaundice 457
Hepatic jaundice 457
Galactose tolerance 457
Serum albumin 458
Prothrombin time 458
Hippuric acid synthesis 458
Choice of liver functions tests 458
Kidney (renal) function tests 459
The formation of urine 459
Renal threshold substances 460
Tests to assess renal function 460
Clearance tests 460
Creatinine clearance test 461
Procedure 461
Modified procedure 461
Reference values 461
Diagnostic importance 461
Urea clearance test 461
Standard urea clearance 462
Diagnostic importance 462
Urine concentration test 462
Osmolality and specific gravity 462
Analysis of blood (or serum) 462
Urine examination 463
Choice of renal function tests 463
Gastric function tests 463
Secretion of gastric HCI 463
Tests to assess gastric function 464
Fractional test meal (FTM) 464
Alcohol test meal 464
Pentagastrin stimulation test 464
Augmented histamine test meal 464
Insulin test meal 464
Tubeless gastric analysis 464
Abnormalities of gastric function 464
Other organ function tests 464
Pancreatic function tests 464
Pancreatic enzymes in serum 464
Thyroid function tests 464
Self Assessment excercises 465
Chapter 20 465
Chapter 21 - Water, Electrolyte and Acid-base Balance 468
Water and life 468
Functions of water 468
Distribution of water 468
Water turnover and balance 469
Water intake 469
Exogenous water 469
Endogenous water 469
Water output 469
Urine 469
Hormonal regulation of urine production 469
Skin 469
Lungs 470
Feces 470
Electrolyte balance 470
Electrolyte composition of body fluids 470
Osmolarity and osmolality of body fluids 470
Osmolality of plasma 471
Osmolality of ECF and ICF 471
Regulation of electrolyte balance 472
Aldosterone 472
Antidiuretic hormone (ADH) 472
Renin-angiotensin 472
Atrial natriuretic factor (ANF) 472
Na+ concentration and ECF 472
Dietary intake and electrolyte balance 472
Dehydration 472
Causes of dehydration 472
Characteristic features of dehydration 473
Treatment 473
Osmotic imbalance and dehydration in cholera 473
Overhydration 473
Water tank model 473
Metabolism of electrolytes 473
Diuretics in the treatment of edema and hypertension 474
Acid-base balance 474
Production of acids by the body 474
Production of bases by the body 474
Maintenance of blood pH 475
I. Blood buffers 475
Blood pH and the ratio of HCO3- to H2CO3 475
II. Respiratory mechanism for pH regulation 476
Hemoglobin as a buffer 476
Generation of HCO3- by RBC 476
III. Renal mechanism for pH regulation 477
Urine pH normally lower than blood pH 477
Carbonic anhydrase and renal regulation of pH 477
Carbon dioxideŠthe central molecule of pH regulation 479
Buffers of intracellular fluids 479
Disorders of acid-base balance 479
Clinical causes of acid-base disorders 480
Compensation of acid-base disorders 480
Anion gap 480
Metabolic acidosis 481
Anion gap and metabolic acidosis 481
Compensation of metabolic acidosis 482
Respiratory acidosis 482
Metabolic alkalosis 482
Respiratory alkalosis 482
Mixed acid-base disorders 483
Acid-base disorders and plasma potassium 483
Potassium and diabetic ketoacidosis 483
Potassium and alkalosis 483
Blood gas measurement 483
Self-assessment exercises 485
Chapter 21 485
Chapter 22 - Tissue Proteins and Body Fluids 487
Connective tissue proteins 487
Collagen 487
Functions of collagen 487
Types of collagen 487
Structure of collagen 487
Biosynthesis of collagen 487
Abnormalities associated with collagen 487
Scurvy 487
Lathyrism 487
Elastin 487
Abnormalities associated with elastin 487
Fibrillin 487
Fibronectin 487
Laminin 487
Keratins 487
Hair waving (curling) 487
Proteoglycans 487
Contractile proteins 487
Structure of muscle 487
Muscle proteins 487
Actin 487
Tropomyosin and troponin 487
Myosins 487
Light and heavy meromyosins 487
Muscle contraction 487
Sources of ATP for muscle contraction 487
Other proteins of muscle 487
Muscular dystrophy 487
Protein misfolding and diseases 487
Amyloidosis 487
Body fluids 487
Milk 487
Composition of milk 487
Carbohydrates in milk 487
Lipids in milk 487
Proteins in milk 487
Whey proteins 487
Minerals in milk 487
Vitamins in milk 487
Calorific value of milk 487
Cerebrospinal fluid (CSF) 487
Functions of CSF 487
Collection of CSF 487
Composition of CSF in health and disease 487
Amniotic fluid 487
Functions of amniotic fluid 487
Diagnostic importance of amniotic fluid 487
Assessment of fetal maturity 487
Lung maturity 487
Diagnosis of congenital disorders 487
Assessment of hemolytic diseases 487
Measurement of a-fetoprotein 487
Pleural fluid 487
Aqueous humor 487
Self-assessment excercises 487
Chapter 22 487
Chapter 23 - Nutrition 502
Methodology in nutrition 502
Study of human nutrition 502
Nutrition and energy supply 502
Energy content of foods 503
Unit of heat 503
Calorie value of foods 503
Respiratory quotient of foodstuffs 503
Carbohydrates 503
Fats 503
Proteins 503
Mixed diet 503
Utilization of energy in man 503
Basal metabolic rate 504
Measurement of BMR 504
Preparation of the subject 504
Measurement 504
Units of BMR 504
Normal values of BMR 504
Factors affecting BMR 504
Significance of BMR 505
Specific dynamic action 505
SDA for different foods 505
SDA for mixed diet 505
Significance of SDA 505
Mechanism of SDA 505
Physical activity of the body 506
Energy requirements of man 506
Nutritional importance of carbohydrates 506
Functions of carbohydrates 507
High fructose corn syrups (HFCS) 507
Glycemic index 507
Sources of carbohydrates 508
Requirement of carbohydrates 508
Fiber in nutrition 508
Beneficial effects of fiber 508
Adverse affects of fiber 509
Sources of dietary fiber 509
Nutritional importance of lipids 509
Major nutritional functions of lipids 509
Essential fatty acids 509
Functions of EFA 509
Deficiency of EFA 510
EFA content of foods 510
Dietary intake of EFA 510
ω-3 and ω-6 fatty acids 510
Trans fatty acids (tfa) 510
Cholesterol in nutrition 510
Requirement of dietary fat 510
Nutritional importance of proteins 510
Functions of proteins 510
Essential amino acids 511
Nitrogen balance 511
Positive nitrogen balance 511
Negative nitrogen balance 511
Other factors influencing nitrogen balance 511
Hormones 512
Disease states 512
Assessment of nutritive value of proteins 512
Protein efficiency ratio (PER) 512
Biological value (BV) 512
Net protein utilization (NPU) 512
Chemical score 512
Mutual supplementation of proteins. 513
Requirement of proteins 513
Dietary sources of proteins 514
Nutritional importance of vitamins and minerals 514
Recommended dietary allowances (rda) 514
Factors affecting RDA 514
RDA an for adult man 514
Balanced diet 514
Balanced diet in developed countries 515
Nutritional disorders 515
Protein–energy malnutrition 516
Kwashiorkor 516
Occurrence and causes 516
Clinical symptoms 516
Biochemical manifestations 516
Treatment 516
Marasmus 516
Signs comparable to marasmus in advanced cancer and AIDS 516
Nutritional anemias 516
Other nutritional disorders 517
Therapeutic diets 517
Atkins diet 517
Nutritional status and clinical practice 518
Drug and nutrient interactions 518
Nutrigenomics 518
Self-assessment excercises 519
Chapter 23 519
Section V - Molecular Biology and Biotechnology 522
Chapter 24 - DNAŒReplication, Recombination, and Repair 523
Why did DNA evolve as genetic material? 523
The central dogma of life 523
Replication of DNA 523
Replication in prokaryotes 523
Replication is semiconservative 523
Initiation of replication 523
Replication bubbles 523
RNA primer 523
DNA synthesis is semidiscontinuous and bidirectional 523
Replication fork and DNA synthesis 523
DNA helicases 523
Single-stranded DNA binding (SSB) proteins 523
DNA synthesis catalysed by DNA polymerase III 523
Polarity problem 523
Okazaki pieces 523
Proof-reading function of DNA polymerase III 523
Replacement of RNA primer by DNA 523
Supercoils and DNA topoisomerases 523
Replication in Eukaryotes 523
Process of replication in Eukaryotes 523
Inhibitors of dna replication 523
Cell cycle and DNA replication 523
Cyclins and cell cycle 523
Cell cycle check points 523
Cancer and cell cycle 523
Telomeres and Telomerase 523
Role of telomerase 523
Telomere in senescence and cancer 523
Recombination 523
Homologous recombination 523
Holliday model 523
Non-homologous recombination 523
Transposition 523
Retrotransposition 523
DNA transposition 523
Significance of transposition 523
Damage and repair of DNA 523
Consequences of DNA damage 523
Types of DNA damages 523
Mutations 523
Types of mutations 523
Consequences of point mutations 523
Consequences of frameshift mutations 523
Mutations and cancer 523
Repair of DNA 523
Base excision-repair 523
Nucleotide excision-repair 523
Mismatch repair 523
Double-strand break repair 523
Defects in DNA repair and cancer 523
Self-assessment exercises 523
Answers to Self-assessment Exercises 523
Chapter 25 - Transcription and Translation 542
Genome 542
Genomics 542
Transcriptome 542
Transcriptomics 542
Proteome 542
Proteomics 542
Metabolomics 542
Transcription 542
Transcription is selective 542
Transcription in prokaryotes 542
Initiation 542
Elongation 542
Termination 542
Transcription in eukaryotes 542
RNA polymerases 542
Promoter sites 542
Initiation of transcription 542
Heterogeneous nuclear RNA (hnRNA) 542
Post-transcriptional modifications 542
Messenger RNA 542
Different mRNAs produced by alternate splicing 542
Faulty splicing can cause diseases 542
mRNA editing 542
Transfer RNA 542
Ribosomal RNA 542
Inhibitors of transcription 542
Actinomycin 542
Rifampin 542
a-Amanitin 542
Cellular RNA contents 542
Reverse transcription 542
Synthesis of cDNA from mRNA 542
Translation 542
Variability of cells in translation 542
Genetic code 542
Other characteristics of genetic code 542
Codon-anticodon recognition 542
Wobble hypothesis 542
Codon bias 542
Mutations and genetic code 542
Protein biosynthesis 542
I. Requirement of the components 542
II. Activation of amino acids 542
III. Protein synthesis proper 542
Initiation of translation 542
Ribosomal dissociation 542
Formation of 43S preinitiation complex 542
Formation of 48S initiation complex 542
Recognition of initiation codon 542
Formation of 80S initiation complex 542
Regulation of initiation 542
Initiation of translation in prokaryotes 542
Elongation of translation 542
Binding of aminoacylŠtRNA to A-site 542
Peptide bond formation 542
Translocation 542
Incorporation of amino acids 542
Termination of translation 542
Inhibitors of protein synthesis 542
Streptomycin 542
Tetracycline 542
Puromycin 542
Chloramphenicol 542
Erythromycin 542
Diphtheria toxin 542
IV. Chaperones and protein folding 542
Types of chaperones 542
Protein misfolding and diseases 542
V. Post-translational modifications of proteins 542
Proteolytic degradation 542
Intein splicing 542
Covalent modifications 542
Protein targeting 542
Protein targeting to mitochondria 542
Protein targeting to other organelles 542
Mitochondrial dna, transcription and translation 542
Self-assessment exercises 542
Answers to Self-assessment Exercises 542
Chapter 26 - Regulation of Gene Expression 566
Gene regulationŠgeneral 566
Constitutive and inducible genes 566
One cistron-one subunit concept 566
Models to study gene expression 566
The operon concept 566
Lactose (lac) operon 566
Structure of lac operon 566
Repression of lac operon 566
Derepression of lac operon 566
Gratuitous inducers 566
The catabolite gene activator protein 566
Tryptophan operon 566
Tryptophan operon regulation by a repressor 566
Attenuator as the second control site for tryptophan operon 566
Gene expression in eukaryotes 566
Chromatin sructure and gene expression 566
Histone acetylation and deacetylation 566
Methylation of DNA and inactivation of genes 566
Enhancers and tissue-specific gene expression 566
Combination of dna elements and proteins in gene expression 566
Motifs in proteins and gene expression 566
Helix-turn-helix motif 566
Zinc finger motif 566
Leucine zipper motif 566
Helix-loop-helix motif 566
Gene regulation in eukaryotes 566
Gene amplification 566
Gene rearrangment 566
Processing of RNA 566
Alternate mRNA splicing 566
Degradation of mRNA 566
Epigenetic regulation of gene expression 566
Epigenetic therapy of cancers 566
Self-assessment exercises 566
Answers to Self-assessment Exercises 566
Chapter 27 - Recombinant DNA and Biotechnology 578
Brief history of recombinant DNA technology 578
Basic principles of rDNA technology 578
Molecular tools of genetic engineering 578
Restriction endonucleasesŠ DNA cutting enzymes 578
Nomenclature 578
Recognition sequences 578
Cleavage patterns 578
DNA ligasesŠDNA joining enzymes 578
Host cellsŠ the factories of cloning 578
Prokaryotic hosts 578
Escherichia coli 578
Bacillus subtilis 578
Eukaryotic hosts 578
Mammalian cells 578
VectorsŠ the cloning vehicles 578
Plasmid 578
Nomenclature of plasmids 578
pBR322 Œ the most common plasmid vector 578
Other plasmid cloning vectors 578
Bacteriophages 578
Cosmids 578
Artificial chromosome vectors 578
Human artificial chromosome (HAC) 578
Yeast artificial chromosomes (YACs) 578
Bacterial artificial chromosomes (BACs) 578
Choice of vector 578
Methods of gene transfer 578
Transformation 578
Conjugation 578
Electroporation 578
Liposome-mediated gene transfer 578
Direct transfer of DNA 578
Gene cloning strategies 578
Cloning from genomic dna or mRNA? 578
Basic techniques in genetic engineering 578
Isolation and purification of nucleic acids 578
Purification of cellular DNA 578
Lysis of cells 578
Bacterial cells 578
Animal cells 578
Plant cells 578
Methods to purify DNA 578
Purification of mRNA 578
Nucleic acid blotting techniques 578
Types of blotting techniques 578
Southern blotting 578
Zoo blot 578
Applications of Southern blotting 578
Northern blotting 578
Dot-blotting 578
Western blotting 578
Autoradiography 578
Applications of autoradiography 578
DNA Sequencing 578
Maxam and gilbert technique 578
Dideoxynucleotide method 578
Termination role of dideoxynucleotide 578
Sequencing method 578
Modifications of dideoxynucleotide method 578
Automated dna sequencing 578
Advantages of automated sequencing 578
DNA chips (microarrays) 578
Technique of DNA sequencing 578
Applications of DNA chips 578
The future of DNA chips 578
Polymerase Chain Reaction (DNA Amplification) 578
Principle of PCR 578
Technique of PCR 578
Sources of DNA polymerase 578
Variations of PCR 578
Applications of PCR 578
PCR in clinical diagnosis 578
Prenatal diagnosis of inherited diseases 578
Diagnosis of retroviral infections 578
Diagnosis of bacterial infections 578
Diagnosis of cancers 578
PCR in sex determination of embryos 578
PCR in DNA sequencing 578
PCR in comparative studies of genomes 578
PCR in forensic medicine 578
Gene libraries 578
Establishing a gene library for humans 578
Screening strategies 578
Screening by DNA hybridization 578
Site-directed mutagenesis and protein engineering 578
Tissue plasminogen activator (tPA) 578
Hirudin 578
DNA in disease diagnosis and medical forensics 578
Methods of dna assay 578
Nucleic acid hybridization 578
The DNA chip-microarray of gene probes 578
Technique for use of DNA chip 578
Applications of DNA chip 578
DNA in the diagnosis of infectious diseases 578
Tuberculosis 578
Malaria 578
Acquired immunodeficiency syndrome (AIDS) 578
DNA in the diagnosis of genetic diseases 578
Sickle-cell anemia 578
Gene banks Ša novel concept 578
DNA fingerprinting or DNA profiling 578
History and terminology 578
Applications of DNA fingerprinting 578
DNA markers in disease diagnosis and fingerprinting 578
Restriction fragment length polymorphisms (rflps) 578
RFLPs in the diagnosis of diseases 578
Methods of RFLP scoring 578
Applications of RFLPs 578
Variable Number Tandem Repeats (VNTRs) 578
Limitations of VNTRs 578
Use of RFLPs and VNTRs in genetic fingerprinting 578
Microsatellites (Simple tandem repeats) 578
Single Nucleotide Polymorphisms (SNPs) 578
Current technology of DNA Fingerprinting 578
Pharmaceutical products of DNA technology 578
Insulin and diabetes 578
Production of recombinant insulin 578
Technique for production of recombinant insulin 578
Recombinant vaccines 578
Hepatitis B vaccine Šthe first synthetic vaccine 578
Hepatitis B vaccine in India 578
DNA Vaccines (genetic immunization) 578
Dna vaccine and immunity 578
Humoral immunity 578
Cellular immunity 578
Transgenic animals 578
Importance of transgenic animalsŠgeneral 578
Transgenic mice and their applications 578
Animal bioreactors 578
Dolly Œ the transgenic clone 578
Cloning of pet animals 578
Biotechnology and society 578
Benefits of biotechnology 578
ELSI of Biotechnology 578
Risks and ethics of biotechnology 578
Self-assessment exercises 578
Answers to Self-assessment Exercises 578
Section VI - Current Topics 617
Chapter 28 - Human Genome Project 619
The birth and activity of human genome project 619
Announcement of the draft sequence of human genome 619
Mapping of the human genome 619
Approaches for genome sequencing 619
Whose genome was sequenced? 619
Human genome sequenceŠ results summarised 619
Most of the genome sequence is identified 619
Individual differences in genomes 619
Organization of human genome 619
Genes present in human genome 619
Human genes encoding proteins 619
Benefits/applications of human genome sequencing 619
Ethics and human genome 619
Chapter 29 - Gene Therapy 625
Approaches for gene therapy 625
Ex vivo gene therapy 625
Vectors in gene therapy 625
Viruses 625
Human artificial chromosome 625
Bone marrow cells 625
Selected examples of ex vivo gene therapy 625
Therapy for adenosine deaminase deficiency 625
Severe combined immunodeficiency (SCID) 625
Technique of therapy for ADA deficiency 625
Transfer of ADA gene into stem cells 625
In vivo gene therapy 625
Gene delivery by viruses 625
Gene delivery by non-viral systems 625
Gene therapy strategies for cancer 625
Tumor necrosis factor gene therapy 625
Suicide gene therapy 625
Gene replacement therapy 625
Antigene and antisense therapy 625
Antisense therapy for cancer 625
Peptide nucleic acid (PNA) therapy 625
The future of gene therapy 625
Chapter 30 - Bioinformatics 634
History and relevance of bioinformatics 634
Broad coverage of Bioinformatics 634
Functional genomics 634
Structural genomics 634
Comparative genomics 634
DNA microarrays 634
Medical informatics 634
Components of Bioinformatics 634
Bioinformatics and the Internet 634
World wide web (www) 634
Biological databases 634
Nucleotide sequence databases 634
Protein sequence databases 634
Molecular structure of databases 634
Other databases 634
Applications of Bioinformatics 634
Chapter 31 - Metabolism of Xenobiotics (Detoxification) 638
DetoxificationŠa misnomer? 638
Site of detoxification 638
Mechanism of detoxification 638
Phase I 638
Phase II 638
Oxidation 638
Alcohols 638
Aldehydes 638
Amines and their derivatives 638
Aromatic hydrocarbons 638
Sulfur compounds 638
Drugs 638
Role of cytochrome P450 638
Salient features of cytochrome P450 638
Reduction 638
Hydrolysis 638
Conjugation 638
Glucuronic acid 638
Glycine 638
Glutathione 638
Glutamine 638
Methyl group 638
Sulfate 638
Acetic acid 638
Thiosulfate 638
Detoxification by drugs 638
Chapter 32 - Prostaglandins and Related Compounds 644
History 644
Structure of prostaglandins 644
Synthesis of prostaglandins 644
CyclooxygenaseŒa suicide enzyme 644
Inhibition of PG synthesis 644
Aspirin inhibits PG synthesis 644
Degradation of prostaglandins 644
Biochemical actions of prostaglandins 644
Low doses of aspirin reduce heart attacks 644
Biomedical applications of PGs 644
Leukotrienes 644
Dietary marine lipids in relation to PGs, LTs and heart diseases 644
Chapter 33 - Biological Membranes and Transport 650
Chemical composition 650
Structure of membranes 650
Transport across membranes 650
Mechanism of facilitated diffusion 650
Na+-K+ pump 650
Na+-cotransport system 650
Transport systems 650
Cotransport system 650
Proton pump in the stomach 650
Passive transport of water-osmosis 650
Transport of macromolecules 650
Diseases due to loss of membrane transport systems 650
Chapter 34 - Free Radicals and Antioxidants 655
Types of free radicals 655
Free radicals and reactive oxygen species (ROS)Šnot synonymous 655
Sources and generation of free radicals 655
Lipid peroxidation 655
Initiation phase 655
Propagation phase 655
Termination phase 655
Malondialdehyde (MDA) as a marker for lipid peroxidation 655
Generation of ROS by macrophages 655
Medical applications of ROS 655
Harmful effects of free radicals 655
Free radicals and biomolecules 655
Proteins 655
Lipids 655
Carbohydrates 655
Nucleic acids 655
Free radicals and diseases 655
Cardiovascular diseases (CHD) 655
Cancer 655
Inflammatory diseases 655
Respiratory diseases 655
Diabetes 655
Cataract 655
Male infertility 655
Aging process 655
Other diseases 655
Antioxidants in biological system 655
I. Antioxidants in relation to lipid peroxidation 655
II. Antioxidants according to their location 655
III. Antioxidants according to their nature and action 655
The antioxidant enzyme system 655
Superoxide dismutase 655
Catalase 655
Glutathione peroxidase 655
Nutrient antioxidants 655
Tocopherols (vitamin E) 655
Ascorbic acid (vitamin C) 655
Carotenoids 655
Selenium 655
a-Lipoic acid 655
Caffeine 655
Metabolic antioxidants 655
Glutathione 655
Dietary supplementation of antioxidants 655
Chapter 35 - Environmental Biochemistry 662
Atmospheric (climatic) changes 662
Exposure to cold 662
Non-shivering phase 662
Exposure to heat 662
Heat stroke 662
Environmental pollution 662
Air pollution 662
Sulfur dioxide 662
Carbon monoxide 662
Carbon dioxide 662
Nitrogen dioxide 662
Hydrocarbons 662
Particulates 662
Ozone layer 662
Water pollution 662
Organic pollutants 662
Water-borne disease agents 662
Oxygen demanding wastes 662
Organic chemicals 662
Pesticides 662
Inorganic pollutants 662
Lead 662
Mercury 662
Cadmium 662
Aluminium 662
Arsenic 662
Noise pollution 662
Radioactive pollution 662
Toxic compounds in foodstuffs 662
Natural toxins in foodstuffs 662
Neurotoxins 662
Protease inhibitors 662
Goitrogens 662
Biogenic amines 662
Anti-vitamins 662
Toxic pollutants of foodstuffs 662
Cultivation 662
Processing 662
Storage 662
Carcinogens 662
Chapter 36 - Insulin, Glucose Homeostasis, and Diabetes Mellitus 669
Chapter 37 - Cancer 685
Incidence 685
Etiology 685
Chemical carcinogens 685
Mechanism of action 685
Ames assay 685
Promoters of carcinogenesis 685
Radiation energy 685
Carcinogenic viruses 685
DNAŠthe ultimate in carcinogenesis 685
Molecular basis of cancer 685
Oncogenes 685
Activation of protooncogenes to oncogenes 685
Mechanism of action of oncogenes 685
Growth factors 685
Growth factor receptors 685
GTP-binding proteins 685
Non-receptor tyrosine kinases 685
Antioncogenes 685
Genes that regulate apoptosis 685
Unified hypothesis of carcinogenesis 685
Tumor markers 685
Characteristics of growing tumor cells 685
Metastasis 685
Cancer therapy 685
Prevention of cancer 685
Chapter 38 - Acquired Immunodeficiency Syndrome (AIDS) 695
Epidemiology 695
Transmission of HIV 695
Virology of HIV 695
Structure of HIV 695
Genome and gene products of HIV 695
Immunological abnormalities in AIDS 695
Entry of HIV and lysis of CD4 cells 695
Other immunological abnormalities 695
Abnormalities of central nervous system : 695
Consequences of immunodeficiency 695
Natural course of AIDS 695
Laboratory diagnosis of AIDS 695
Drugs for the treatment of AIDS 695
Mechanism of action 695
Vaccine against AIDS Ša failure so far 695
Section VII - Basics to Learn Biochemistry 701
Chapter 39 - Introduction to Bioorganic Chemistry 703
Most common organic compounds found in living system 703
Common functional groups in biochemistry 703
Common ring structures in biochemistry 703
Homocyclic rings 703
Heterocyclic rings 703
Isomerism 703
Structural isomerism 703
Stereoisomerism 703
Geometrical isomerism 703
Optical isomerism 703
What is an asymmetric carbon? 703
What is optical activity? 703
Configuration of chiral molecules 703
Existence of chiral biomolecules 703
Chapter 40 - Overview of Biophysical Chemistry 708
Water 708
Structure of water 708
Hydrogen bonds between H2O molecules 708
Water expands on freezing 708
Acids and bases 708
Alkalies 708
Ampholytes 708
Dissociation of water 708
Hydrogen ion concentration (pH) 708
Buffers 708
Mechanism of buffer action 708
Buffering capacity 708
Solutions 708
Per cent concentration 708
Parts per million (ppm) 708
Molarity (M) 708
Molality 708
Normality 708
Chapter 41 - Tools of Biochemistry 719
Chromatography 719
Historical perspective 719
Principles and classification 719
Electrophoresis 719
Different types of electrophoresis 719
PhotometryŠcolorimeter and spectrophotometer 719
Colorimeter 719
Spectrophotometer 719
Fluorimetry 719
Flame photometry 719
Ultracentrifugation 719
Isolation of subcellular organelles by centrifugation 719
Radioimmunoassay 719
Chapter 42 - Immunology 732
Innate immunity 732
First line of defense 732
Second line of defense 732
The immune system 732
Organization of immune system 732
Primary lymphoid organs 732
Secondary lymphoid organs 732
Cells of the immune system 732
B-lymphocytes 732
T-lymphocytes 732
Major histocompatibility complex 732
The complement system 732
Nomenclature of complement system 732
Types of reaction 732
The immune response 732
Cytokines 732
Therapeutic uses of cytokines 732
Immunity in health and disease 732
Autoimmune diseases 732
Mechanism of autoimmunity 732
Organ transplantation 732
Cancers 732
Aids 732
Chapter 43 - Genetics 737
The blood theory of inheritance in humans 737
Brief history and development of genetics 737
Mendel's experiments 737
The origin of the word gene 737
Chemical basis of heredity 737
Importance of genes in inheritanceŠstudies on twins 737
Basic principles of heredity in humans 737
Monogenic and polygenic traits 737
Monogenic disorders 737
Polygenic disorders 737
Patterns of inheritance 737
Genetic diseases in humans 737
Aneuploidy 737
Eugenics 737
Eugenics in Nazi Germany 737
Section VIII - Appendices 743
Answers to Self-assessment Exercises 745
Appendix I : Abbreviations used in this Book 751
Appendix II : Origins of Important Biochemical Words 756
Appendix III : Common Confusables in Biochemistry 759
Appendix IV : Practical Biochemistry—Principles 763
Appendix V : Clinical Biochemistry Laboratory 769
Appendix VI : Case Studies with Biochemical Correlations 772
Appendix VII : Reference Biochemical Values\r 778a
Index 779