Contents

Section 1: Chemical Basis of Life

1. Biochemical Perspective to Medicine 3
Historical Background of Biochemistry  3; Biomolecules 4;  Study of Metabolic Processes  5;
Stabilizing Forces in Molecules  5;  Water: The Universal Solvent  6;  Principles of Thermodynamics  7;
Donnan Membrane Equilibrium  7; Osmosis 8; Dialysis 10;  Equivalent Weight  10;
Molecular Weight  10

2. Subcellular Organelles and Cell Membranes 12

Subcellular Organelles  12;  Plasma Membrane  15;  Bacterial Cell Wall  17;
Specialized Membrane Structures  17; Cytoskeleton 18;  Transport Mechanisms  18;
Transport of Large Molecules   22

3. Amino Acids and Proteins 28

Classification of Amino Acids  28;  Properties of Amino Acids  31;
General Reactions of Amino Acids  33;  Amino Acid Derivatives of Importance  34;
Proteins and Peptide Bond Formation  34;  Structure of Proteins (Organization of Proteins)  35;
Structure-function Relationship  39;  Study of Protein Structure  40;
Chemical Synthesis of Peptides  41;  Physical Properties of Proteins  42;
Precipitation Reactions of Proteins  42;  Classification of Proteins  43;
Quantitative Estimation of Proteins  44; Proteomics  46

4. Enzymology: General Concepts, Enzyme Kinetics, Isoenzymes and Clinical Enzymology 53

Classification of Enzymes  54; Coenzymes 55; Metalloenzymes 56; Cofactors  57;
Mode of Action of Enzymes  57;  Active Site or Active Center of Enzyme  59;
Thermodynamic Considerations  61;  Enzyme Kinetics  61;  Factors Influencing Enzyme Activity  62;
Specificity of Enzymes  70; Ribozymes 71;  Enzyme Assays and Units  71;
Body Metabolism is Controlled by Enzymes  71;  Drug Metabolism  71;  Enzyme Engineering  72;
Drug Designing  72;  Processive Enzymes  72;  Multienzyme Complexes  72; Isoenzymes 72;
Clinical Enzymology  73

5. Chemistry of Carbohydrates 86
Functions of Carbohydrates  86; Nomenclature 
86; Stereoisomers  86;  Reactions of Monosaccharides  89;
Disaccharides  92; Polysaccharides 
93;  Common Sugar Substitutes  96;  Dietary Fiber  96; Aquasomes 96;
Glycome and Glycomics  96

6. Chemistry of Lipids 100

Classification of Lipids  100
xiv Textbook of Biochemistry
Section 2: GENERAL METABOLISM
7. Overview of Metabolism 115
Experimental Study of Metabolism  115; Metabolism 116;  Metabolic Profile Under Well-fed State  117;
Metabolic Adaptations during Fasting  117;  Metabolic Adaptations during Starvation  117;
Metabolic Profile of Important Organs  119;  Glucose Utilization in Lungs  121;
Metabolic Changes during Pregnancy  122;  Metabolic Changes during Lactation  123;
Metabolic Changes in Trauma and Critical Illness  123;
Importance of Gluconeogenesis in Premature Infants  124;  Lifestyle Diseases  124

8. Metabolic Pathways of Glucose 128

Digestion of Carbohydrates  128;  Absorption of Carbohydrates  128;  Glucose Metabolism  130;
Cori’s Cycle or Lactic Acid Cycle  137;  Metabolic Fate of Pyruvate  138; Gluconeogenesis 139;
Glycogen Metabolism  143;  Glycogen Storage Diseases  147;
Hexose Monophosphate Shunt Pathway  147;  Glucuronic Acid Pathway  152;
Polyol Pathway of Glucose  152

9. Regulation of Blood Glucose, Insulin and Diabetes Mellitus 161

Regulation of Blood Glucose  161;  Reducing Substances in Urine  166; Insulin 167;
Hyperglycemic Hormones  171;  Diabetes Mellitus  172;  Obesity  174

10. Metabolic Pathways of Carbohydrates other than Glucose 186

Fructose Metabolism  186;  Galactose Metabolism  187;  Metabolism of Alcohol  188;
Metabolism of Amino Sugars  190; Glycoproteins 191;
Congenital Disorders of Glycosylation  192; Mucopolysaccharidoses 193

11. Metabolism of Fatty Acids 198

Digestion of Lipids  198;  Absorption of Lipids  199;  Beta-oxidation of Fatty Acids  201;
Oxidation of Odd Chain Fatty Acids  205;  Alpha Oxidation  205;  Omega Oxidation  205;
De Novo Synthesis of Fatty Acids  206;  Synthesis of Triglycerides  210;
Metabolism of Ketone Bodies  213

12. Cholesterol and Lipoproteins 220

Cholesterol  220;  Plasma Lipids  224; Apolipoproteins 226; Chylomicrons 227;
Very Low-density Lipoproteins   227;  Low-density Lipoproteins  227;  High-density Lipoprotein  229;
Free Fatty Acid  231;  Formation of Bile Acids  231

13. Cardiovascular Diseases, Biomarkers of Cvd and Hyperlipidemias 236

Clinical Significance of Cholesterol  236; Atherosclerosis 236;  Cardiac Biomarkers  237;
Hypolipoproteinemias  245; Hyperlipidemias 245;
Rheumatic Fever and Rheumatic Heart Disease (Rheumatic Carditis)  247;
Hypertension  248
 Contents xv
14. Medium Chain Fatty Acid, Polyunsaturated Fatty Acid, Prostaglandins
and Compound Lipids 253
Digestion of Medium Chain Fatty Acids  253;  Very Long Chain Fatty Acids  253;
Monounsaturated Fatty Acids  254;  Polyunsaturated Fatty Acids  254;
Synthesis of Compound Lipids  258

15. General Amino Acid Metabolism: Urea Cycle and One-carbon Metabolism 265
Digestion of Proteins  265;  Absorption of Amino Acids  267;
Intracellular Protein Degradation  267;  Nitrogen Balance   269;
Interorgan Transport of Amino Acids  269;  General Metabolism of Amino Acids  269;
Formation of Ammonia  269;  Disposal or Detoxification of Ammonia  271;
Urea Cycle  272;  Hyperammonemia   276;  One-carbon Metabolism  277

16. Metabolism of Aliphatic Amino Acids (Glycine, Serine, Methionine, Cysteine,

Glutamic Acid, Aspartic Acid, Lysine, Arginine, Nitric Oxide, Histidine, Valine,
Leucine and Isoleucine) 282
Glycine  282; Serine 286; Alanine 287; Threonine 288; Methionine  288; Cysteine 290;
Metabolism of Sulfur  291;  Glutamic Acid  294; Glutamine 295;  Aspartic Acid  296;
Asparagine  296; Lysine 296; Arginine 297;  Nitric Oxide  297; Polyamines 299;
Branched-chain Amino Acids  300

17. Aromatic and Heterocyclic Amino Acids (Phenylalanine, Tyrosine, Tryptophan,

Histidine and Proline) 306
Phenylalanine  306; Tyrosine 307;  Inborn Errors Associated with Phenylalanine  310;
Tryptophan  313; Histidine 316;  Proline and Hydroxyproline  317;
Fate of Carbon Skeletons of Amino Acids   318; Aminoacidurias 318

18. Inborn Errors of Metabolism, Prenatal Screening and Newborn Screening 324
General Considerations  324;  Tests for Metabolic Disorders in Newborn  325;
Important Inborn Errors of Metabolism  327;  Prenatal Diagnosis  328;
Prenatal Screening  329;  Newborn Screening  331

19. Citric Acid Cycle, Biological Oxidation and Electron Transport Chain 334
Citric Acid Cycle  334;  Stages of Oxidation of Foodstuffs  341;  Redox Potentials  342;
Biological Oxidation  343;  High Energy Compounds  345;  Electron Transport Chain  346;
Mitochondrial Transport Systems  354;  Diseases Associated with Mitochondria  354

20. Heme and Hemoglobin (Pigment Metabolism) 360

Heme  360;  Catabolism of Heme  367;  Plasma Bilirubin  369;  Structure of Hemoglobin  372;
Transport of Oxygen by Hemoglobin  373;  Transport of Carbon Dioxide  375;
Embryonic Hemoglobins  376;  Fetal Hemoglobin   376;  Hemoglobin A2  377;
Hemoglobin Derivatives  377;  Hemoglobin (Globin Chain) Variants  378; Anemias  383
xvi Textbook of Biochemistry
Section 3: CLINICAL AND APPLIED BIOCHEMISTRY
21. Liver and Gastric Function Tests 395
Functions of Liver  396;  Clinical Manifestations of Liver Dysfunction   397;
Liver Function Tests  397;  Reye Syndrome (Hepatic Mitochondrial Damage)  403;
Gastric Function  403;  Pancreatic Function Tests  405;  Studies on Malabsorption  406

22. Kidney Function Tests 410

Renal Function Tests  410;  Abnormal Constituents of Urine  412;  Markers of Gfr  414;
Markers of Glomerular Permeability  418;  Tests for Tubular Function  420;
Immunological Tests in Renal Diseases  421

23. Plasma Proteins 425

Electrophoresis  425; Albumin 427;  Transport Proteins  429;  Acute Phase Proteins  430;
Clotting Factors  431

24. Acid-base Balance and ph 437

Acids and Bases  438; Buffers 439;  Buffers of the Body Fluids  439;
Respiratory Regulation of ph  441;  Renal Regulation of ph  441;
Cellular Buffers  444;  Disturbances in Acid-base Balance  444;
Assessment of Acid-base Parameters  449;  Normal Serum Electrolyte Values  450

25. Water Balance, Electrolyte Balance (Sodium, Potassium, Chloride,

Magnesium) and Body Fluids 455
Water Balance  455;  Sodium   460;  Potassium   461;  Chloride   464;
Magnesium   464;  Body Fluids  465

26. Free Radicals and Antioxidants 471

Generation of Free Radicals  472;  Free Radical Scavenger Systems  472;
Damage Produced by Reactive Oxygen Species  473;  Clinical Significance  474;
Lipid Peroxidation  475;  Role of Antioxidants  476

27. Detoxification and Biotransformation of Xenobiotics 478

Phase One Reactions  479;  Phase Two Reactions: Conjugations  480;  Phase Three Reactions  482

Section 4: NUTRITION
28. Fat Soluble Vitamins (A, D, E and K) 487
Vitamin A  488;  Vitamin D (Cholecalciferol)  492;  Vitamin E  496;  Vitamin K  497

29 Water-Soluble Vitamins (Thiamine, Riboflavin, Niacin, Pyridoxine,

Pantothenic Acid, Biotin, Folic Acid, Vitamin B12 and Ascorbic Acid) 502
B Complex Group of Vitamins  502;  Thiamine (Vitamin B1)  502;  Riboflavin (Vitamin B2)  503;
Niacin  505;  Vitamin B6  507;  Pantothenic Acid  509; Biotin 511;  Folic Acid  512;  Vitamin B12  514;
Choline  517; Inositol 518;  Ascorbic Acid (Vitamin C)  519
 Contents xvii
30. Mineral Metabolism and Abnormalities 527
Calcium (Ca++)  527; Phosphorus 534; Sulfur 535;  Iron (Fe)  536;  Copper (Cu)  541; Iodine 542;
Zinc (Zn)  542; Fluoride 542;  Selenium (Se)  543;  Manganese (Mn)  543;  Molybdenum (Mo)  543;
Cobalt (Co)  544;  Nickel (Ni)  544;  Chromium (Cr)  544;  Lithium (Li)  544

31. Energy Metabolism and Nutrition 549

Calorific Value  549;  Respiratory Quotient  549;  Energy Requirements of a Normal Person  550;
Requirements of Dietary Nutrients  551;  Proximate Principles  551;  Protein Energy Malnutrition  555;
Obesity  556;  Regulators of Appetite  557;  Adipose Tissue Talks to Brain through Factors  557;
Prescription of Diet  557

32. Heavy Metal Poisons and Environmental Pollution 565

Heavy Metal Poisons  565; Corrosives 567;  Cyanide Poisoning  567; Irritants  567;
Pesticides and Insecticides  567;  Occupational and Industrial Hazards  567;  Air Pollutants  568;
Toxic Substances in Foodstuffs  568;  Pollutants in Household  569

Section 5: MOLECULAR BIOLOGY

33. Nucleotides: Chemistry and Metabolism 575
Composition of Nucleotides  575; Nucleosides 576; Nucleotides 576;
Nucleoside Triphosphates  577;  Cyclic Nucleotides   578;  Digestion of Nucleic Acids  578;
Biosynthesis of Purine Nucleotides  578;  Degradation of Purine Nucleotides  582;
Disorders of Purine Metabolism  583;  De Novo Synthesis of Pyrimidine  585;
Disorders of Pyrimidine Metabolism  587;  Deoxyribonucleotide Formation  587;
Combined Regulation of Purine and Pyrimidine Synthesis  587;
Synthesis of Deoxythymidine Nucleotides  587;
Anticancer Agents Acting on Pyrimidine Synthesis or Pyrimidine Analogues  587;
Degradation of Pyrimidine Nucleotides  588

34. Deoxyribonucleic Acid: Structure, Organization and Replication 592

Structure of Dna  593;  Replication of Dna  596;  Elongation of Dna Strand  599;
Discontinuous Synthesis and Okazaki Pieces  599;  Condensation into Chromatin Structure  600;
Modification after Replication  600;  Cell Cycle  600;  Dna Repair Mechanisms  601;
Telomere and Telomerase  603;  Hydrolysis of Dna  603;  Inhibitors of Dna Replication  604

35. Transcription and Translation 607

Ribonucleic Acid  607;  Central Dogma of Molecular Biology  608;  Transcription Process  608;
Protein Biosynthesis  613;  Genetic Code  615;  Translation Process  616; Mitochondrial Dna   621;
Micro-Rna  621; Interfering Rna or Rnai or sirna  621;  Antisense Therapy  622;
Genomics and Proteomics  622

36. Inheritance, Mutations, Cell Cycle and Control of Gene Expression 627
Basic Principles of Heredity  627;  Genetic Disorders  630; Mutations 630;  Cell Cycle  632;
Apoptosis (Programmed Cell Death)  634;  Regulation of Gene Expression  635; Viruses 638
xviii Textbook of Biochemistry
37. Recombinant Dna Technology and Gene Therapy 643
Recombinant Dna Technology  643;  Restriction Endonucleases  644; Vectors 644;
Procedure of Dna Recombination  645;  Gene Library  647;  Linkage Analysis  647;
Crispr-Cas9  648;  Gene Therapy  648;  Animal Cloning  650;  Stem Cells  651

38. Molecular Diagnostics 654

Hybridization Techniques  654;  Applications of Dna Hybridization in Medicine  656;
Polymerase Chain Reaction  658;  Mutation Detection Techniques  660; Dna Sequencing  661;
Next Generation Sequencing  661; Bioinformatics 661; Nanotechnology  662; Aquasomes 662

Section 6: ADVANCED BIOCHEMISTRY

39. Mechanisms of Action of Hormones 667
Hormones Acting through Cyclic Amp  667;  Calcium-based Signal Transduction  670;
Hormones Acting through Pip2 Cascade   670;  Hormones with Intracellular Receptors  671;
Hypothalamic Hormones  672;  Hormones of Anterior Pituitary  673;  Adrenal Cortical Hormones  675;
Sex Hormones  680;  Thyroid Hormones  681;  Gut Hormones  684;
Growth Factors and Growth Factor Receptors  685

40. Immunochemistry 691

Antigens  692;  Immune Response  692;  Structure of Immunoglobulins  693;
Different Classes of Immunoglobulins  693; Paraproteinemias 695;
Complement System  696;  Immunodeficiency States  697;
Primary and Secondary Immune Responses  697;  Transposition of Genes  697;
Gene, Cistron, Split Gene and Polypeptide  698;  Molecular Structure of Antigens  698;
Soluble Factors  698;  Hybridoma Technology and Monoclonal Antibodies  699;
Concepts Involved in Development of Vaccines  700

41. Biochemistry of Aids and Hiv 703

Epidemic of Acquired Immunodeficiency Syndrome   703;  The Human Immunodeficiency Virus  704;
Immunology of Aids  705;  Laboratory Diagnosis  705;  Antihuman Immunodeficiency Virus Drugs  706;
Prevention  706

42. Biochemistry of Cancer 708

Etiology of Cancer  708;  Oncogenic Viruses  709; Oncogenes 711;  Oncosuppressor Genes  712;
Growth Factors  713;  Differences between Normal and Tumor Cells   713;  Tumor Immunology  714;
Tumor Markers  715;  Anticancer Drugs  716

43. Extracellular Matrix and Tissue Proteins in Health and Diseases 720
Extracellular Matrix  720; Collagen 721; Elastin 723; Keratins 724;  Contractile Proteins  724;
Muscle Proteins  724;  Cellular and Subcellular Movements  727;  Lens Proteins  728;  Nerve Cells  728;
Prions  730;  Biochemistry of Aging  732;  Snake Venom   733
 Contents xix
44. Clinical Laboratory Practice: Laboratory Instrumentation, Techniques and Quality Control 736
Electrophoresis  736; Ultracentrifugation 738; Chromatography 738; Immunoassays 741;
Colorimeter  743; Spectrophotometer 744; Chemiluminescence 745;  Flame Photometer  745;
Ion Selective Electrodes  745;  The pH Meter  745; Biosensors 746;  Mass Spectrometry  747;
Interpretation of Laboratory Data  748;  Specimen Collection  750;  Quality Control  751;
Laboratory Safety  752

45. Applications of Isotopes in Medicine 756

Isotopes  756;  Atomic Number and Atomic Weight  757; Radioactivity 757; 
Biological Effects of Radiation  760;  Radiation Protection  761

Clinical Case Study Answers 763

Appendices 777
Appendix I: Abbreviations used in this Book  777
Appendix II: Reference Values (Normal Values)  783
Appendix III: Conversion Chart  787
Appendix IV: Recommended Daily Allowance of Essential Nutrients  788
Appendix V: Composition of Nutrients in Selected Common Food Materials  789

Index 791