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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 |