Textbook of Biochemistry for Medical Students (Seventh Edition)

Books Biochemistry

Textbook of Biochemistry for Medical Students (Seventh Edition)

Textbook of Biochemistry

for Medical Students

(Seventh Edition)


Contents

SECTION A: Chemical Basis of Life

1. Biochemical Perspective to Medicine                            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 8

2. Subcellular Organelles and Cell Membranes              10

Subcellular organelles 10; Nucleus 10; Endoplasmic reticulum 11; Golgi apparatus 12; Lysosomes 12; Peroxisomes 13; Mitochondria 13; Plasma membrane 14; Specialized membrane structures 16; Transport mechanisms 17

3. Amino Acids: Structure and Properties                      24

Classification of amino acids 24; Properties of amino acids 27; General reactions of amino acids 29; Peptide bond formation 31

4. Proteins: Structure and Function                                33

Structure of proteins 34; Study of protein structure 39; Physical properties of proteins 41; Precipitation reactions of proteins 41; Classification of proteins 42; Quantitative estimation 44

5. Enzymology: General Concepts and Enzyme Kinetics      47

Classification of enzymes 48; Co-enzymes 49; Mode of action of enzymes 51; Michaelis-Menten theory 53; Fischer's template theory 53; Koshland's induced fit theory 53; Active site or active center of enzyme 54; Thermodynamic considerations 54; Enzyme kinetics 55; Factors influencing enzyme activity 56; Specificity of enzymes 65; Iso-enzymes 66

6. Chemistry of Carbohydrates                    69

Nomenclature 69; Stereoisomers 70; Reactions of monosaccharides 73; Disaccharides 76; Polysaccharides 78; Heteroglycans 79; Mucopolysaccharides 80; Glycoproteins and mucoproteins 81

7. Chemistry of Lipids                      83

Classification of lipids 83; Fatty acids 84; Saturated fatty acids 85; Unsaturated fatty acids 85; Trans fatty acids 86; Neutral fats 87; Phospholipids 89

 

SECTION B: General Metabolism

8. Overview of Metabolism                  97

Experimental study of metabolism 97; Metabolism 98; Metabolic profile of organs 99

9. Major Metabolic Pathways of Glucose              105

Digestion of carbohydrates 105; Absorption of carbohydrates 106; Glucose metabolism 107; Glycolysis 108; Metabolic fate of pyruvate 115; Gluconeogenesis 117

10. Other Metabolic Pathways of Glucose           123

Glycogen metabolism 123; Degradation of glycogen (glycogenolysis) 124; Glycogen synthesis (glycogenesis) 125; Glycogen storage diseases 128; Hexose monophosphate shunt pathway 129; Oxidative phase 130; Non-oxidative phase 130; Glucuronic acid pathway of glucose 134; Polyol pathway of glucose 135

11. Metabolic Pathways of Other Carbohydrates       137

Fructose metabolism 137; Galactose metabolism 138; Metabolism of alcohol 140; Metabolism of amino sugars 142; Glycoproteins 142

12. Metabolism of Fatty Acids                      147

Digestion of lipids 147; Absorption of lipids 148; Beta oxidation of fatty acids 151; Oxidation of odd chain fatty acids 154; Alpha oxidation 155; Omega oxidation 155; De novo synthesis of fatty acids 156; Synthesis of triacylglycerols 160; Metabolism of adipose tissue 161; Fatty liver and lipotropic factors 162; Metabolism of ketone bodies 163; Ketosis 164

13. Cholesterol and Lipoproteins 169

Biosynthesis of cholesterol 170; Plasma lipids 173; Chylomicrons 175; Very low density lipoproteins 176; Low density lipoproteins 177; High density lipoprotein 179; Free fatty acid 181; Formation of bile acids 182

14. MCFA, PUFA, Prostaglandins and Compound Lipids      184

Monounsaturated fatty acids 185; Polyunsaturated fatty acids 186; Eicosanoids 188; Prostaglandins 188; Synthesis of compound lipids 191

15. General Amino Acid Metabolism (Urea Cycle, One Carbon Metabolism) 196

Digestion of proteins 196; Formation of ammonia 200; Disposal/detoxification of ammonia 203; Urea cycle 203; One-carbon metabolism 207

16. Simple, Hydroxy and Sulfur-containing Amino Acids (Glycine, Serine, Methionine, Cysteine)      210

Glycine 210; Creatine and creatine phosphate 211; Serine 213; Alanine 215; Threonine 215; Methionine 216; Cysteine 217; Cystinuria 219; Homocystinurias 220

17. Acidic, Basic and Branched Chain Amino Acids (Glutamic Acid, Aspartic Acid, Glutamine, Asparagine, Lysine, Arginine, Nitric Oxide, Valine, Leucine, Isoleucine) 223

Glutamic acid 223; Glutamine 224; Glutamate transporters 225; Aspartic acid 226; Asparagine 226; Arginine 226; Nitric oxide 227; Polyamines 229; Branched chain amino acids 230

18. Aromatic Amino Acids (Phenylalanine, Tyrosine, Tryptophan, Histidine, Proline) and Amino Acidurias     232

Phenylalanine 232; Tyrosine 233; Phenylketonuria 236; Alkaptonuria 237; Albinism 238; Hypertyrosinemias 239; Tryptophan 239; Histidine 243; Proline and hydroxyproline 244; Aminoacidurias 245

19. Citric Acid Cycle 247

Regulation of citric acid cycle 253

20. Biological Oxidation and Electron Transport Chain 255

Redox potentials 256; Biological oxidation 256; Enzymes and co-enzymes 257; High energy compounds 258; Organization of electron transport chain 260; Chemiosmotic theory 263

21. Heme Synthesis and Breakdown             270

Structure of heme 270; Biosynthesis of heme 271; Catabolism of heme 276; Hyperbilirubinemias 279

22. Hemoglobin (Structure, Oxygen and Carbon Dioxide Transport, Abnormal Hemoglobins)           283

Structure of hemoglobin 283; Transport of oxygen by hemoglobin 284; Transport of carbon dioxide 287; Hemoglobin derivatives 289; Hemoglobin (globin chain) variants 290; Thalassemias 293; Myoglobin 294; Anemias 295; Hemolytic anemia 295

SECTION C: Clinical and Applied Biochemistry

23. Clinical Enzymology and Biomarkers             301

Clinical enzymology 301; Creatine kinase 302; Cardiac troponins 303; Lactate dehydrogenase 303; Alanine amino transferase 305; Aspartate amino transferase 305; Alkaline phosphatase 305; Prostate specific antigen 306; Glucose-6-phosphate dehydrogenase 307; Amylase 307; Lipase 308; Enolase 308

24. Regulation of Blood Glucose; Insulin and Diabetes Mellitus           311

Regulation of blood glucose 311; Reducing substances in urine 316; Hyperglycemic hormones 322; Glucagon 322; Diabetes mellitus 323; Acute metabolic complications 326

25. Hyperlipidemias and Cardiovascular Diseases       334

Atherosclerosis 334; Plasma lipid profile 336; Risk factors for atherosclerosis 336; Prevention of atherosclerosis 339; Hypolipoproteinemias 341; Hyperlipidemias 342

26. Liver and Gastric Function Tests           346

Functions of liver 346; Clinical manifestations of liver dysfunction 348; Studies on malabsorption 359

27. Kidney Function Tests                           361

Renal function tests 361; Abnormal constituents of urine 364; Markers of glomerular filtration rate 366; Markers of glomerular permeability 371; Tests for tubular function 373

28. Plasma Proteins 378

Electrophoresis 378; Albumin 380; Transport proteins 382;

Acute phase proteins 383; Clotting factors 385; Abnormalities in coagulation 386

29. Acid-Base Balance and pH 390

Acids and bases 390; Buffers 392; Acid-base balance 393; Buffers of the body fluids 393; Respiratory regulation of pH 395; Renal regulation of pH 395; Cellular buffers 397; Disturbances in acid-base balance 397

30. Electrolyte and Water Balance 407

Intake and output of water 407; Osmolality of extracellular fluid 408; Sodium 411; Potassium 413; Chloride 416

31. Body Fluids (Milk, CSF, Amniotic Fluid, Ascitic Fluid) 420

Milk 420; Cerebrospinal fluid 421; Amniotic fluid 422; Ascitic fluid 423

32. Metabolic Diseases 424

Prenatal diagnosis 424; Newborn screening 427; Laboratory investigations to diagnose metabolic disorders 427

33. Free Radicals and Antioxidants 433

Clinical significance 436

34. Clinical Laboratory; Quality Control 439

Reference values 439; Preanalytical variables 440; Specimen collection 441; Quality control 443

35. General Techniques for Separation, Purification and Quantitation 446

Electrophoresis 446; Chromatography 448; Radioimmunoassay 452; ELISA test 453; Colorimeter 455; Autoanalyzer 457; Mass spectrometry 458

SECTION D: Nutrition

36. Fat Soluble Vitamins (A, D, E, K) 463

Vitamin A 464; Vitamin D (cholecalciferol) 469; Vitamin E 473; Vitamin K 474

37. Water Soluble Vitamins - 1 (Thiamine, Riboflavin, Niacin, Pyridoxine, Pantothenic Acid, Biotin) 477

Thiamine (vitamin B1 ) 477; Riboflavin (vitamin B2 ) 479; Niacin 480; Vitamin B6 482; Pantothenic acid 484; Biotin 485

38. Water Soluble Vitamins - 2 (Folic Acid, Vitamin B12 and Ascorbic Acid) 488

Folic acid 488; Vitamin B12 491; Choline 494; Inositol 495; Ascorbic acid (vitamin C) 495; Rutin 499; Flavonoids 499

39. Mineral Metabolism and Abnormalities 502

Calcium 502; Phosphorus 511; Magnesium 512; Sulfur 513; Iron 514; Copper 520; Iodine 521; Zinc 522; Fluoride 522; Selenium 522; Manganese 523; Molybdenum 523; Cobalt 523; Nickel 523; Chromium 523; Lithium 524

40. Energy Metabolism and Nutrition 527

Importance of carbohydrates 530; Nutritional importance of lipids 531; Importance of proteins 532; Protein-energy malnutrition 534; Obesity 536; Prescription of diet 538

41. Detoxification and Biotransformation of Xenobiotics 544

Phase one reactions 545; Phase two reactions; conjugations 546; Phase three reactions 548

42. Environmental Pollution and Heavy Metal Poisons 550

Corrosives 550; Irritants 551; Heavy metal poisons 551; Pesticides and insecticides 553; Occupational and industrial hazards 553; Air pollutants 553

SECTION E: Molecular Biology

43. Nucleotides: Chemistry and Metabolism 559

Biosynthesis of purine nucleotides 563; Uric acid 566; Gout 566; De novo synthesis of pyrimidine 569

44. Deoxyribonucleic Acid: Structure and Replication 574

Structure of DNA 574; Replication of DNA 578; DNA repair mechanisms 582

45. Transcription 587

Ribonucleic acid 587; Transcription process 589

46. Genetic Code and Translation 596

Protein biosynthesis 596; Translation process 599

47. Control of Gene Expression 608

Mutations 612; Classification of mutations 612; Cell cycle 614; Regulation of gene expression 616; Viruses 620

48. Recombinant DNA Technology and Gene Therapy 624

Recombinant DNA technology 624; Vectors 626; Gene therapy 629; Stem cells 631

49. Molecular Diagnostics and Genetic Techniques 633

Hybridization and blot techniques 633; Polymerase chain reaction 638; Mutation detection techniques 641

SECTION F: Hormones

50. Mechanisms of Action of Hormones and Signaling Molecules 649

51. Hypothalamic and Pituitary Hormones 659

Hypothalamic neuropeptides 659; Hormones of anterior pituitary 660

52. Steroid Hormones 664

Adrenal cortical hormones 664; Sex hormones 669

53. Thyroid Hormones 672

54. Gut Hormones 678

SECTION G: Advanced Biochemistry

55. Immunochemistry 685

Structure of immunoglobulins 687; Paraproteinemias 690; Complement system 691; Immunodeficiency states

56. Biochemistry of AIDS and HIV 699

The human immunodeficiency virus 701; Anti-HIV drugs 703

57. Biochemistry of Cancer 705

Oncogenic viruses 707; Oncogenes 709; Tumor markers 713; Anticancer drugs 716

58. Tissue Proteins in Health and Disease 720

Collagen 720; Elastin 723; Muscle proteins 724; Lens proteins 727; Prions 727; Biochemistry of aging 730

59. Applications of Isotopes in Medicine 732

Isotopes 733; Radioactivity 733; Biological effects of radiation 738

60. Signal Molecules and Growth Factors 740


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Preface to the Seventh Edition

We are glad to present the Seventh edition of the Textbook of Biochemistry for Medical Students. Now, this textbook is entering the 19th year of existence. With humility, we may state that the medical community of India has warmly received the previous editions of this book. The Medical Council of India has accepted it as one of the standard textbooks. We are happy to note that this book has also reached in the hands of medical students of neighboring countries of Nepal, Pakistan, Bangladesh, Sri Lanka, etc. and also to distant countries in Africa and Europe. We are very proud to report that the Textbook has a Spanish edition, with wide circulation in the Central and South America. Apart from the medical community, this book has also become popular to other biological group of students in India. In retrospect, it gives immense satisfaction to note that this book served the students and faculty for the past two decades.

We are bringing out the new edition of the textbook every 3 years. A major addition of this edition is the incorporation of clinical case studies in almost all chapters. We hope that this feature will help the students to identify the clinical relevance of the biochemistry. Further, chapters on clinical chemistry have been extensively updated and clinically relevant points were further added. Rapid progress has been made in the area of molecular biology during past few years, and these advances are to be reflected in this book also. The major change in this Seventh edition is that advanced knowledge has been added in almost all chapters, clinical case studies have been added in relevant chapters; and a few new chapters were added. The print fonts and font size have also been changed for better readability.

From the First edition onwards, our policy was to provide not only basic essentials but also some of the advanced knowledge. About 30% contents of the previous editions were not required for a student aiming for a minimum pass. A lot of students have appreciated this approach, as it helped them to pass the postgraduate (PG) entrance examinations at a later stage. However, this asset has paved the way for a general criticism that the extra details are a burden to the average students. Especially, when read for the first time, the student may find it difficult to sort out the essential minimum from the desirable bulk. In this Seventh edition, advanced topics are given in small prints. In essence, this book is composed of three complementary books. The bold printed areas will be useful for the student at the time of revision just before the examinations; regular printed pages are meant for an average first year MBBS student and the fine printed paragraphs are targeted to the advanced students preparing for the PG entrance. Essay questions, short notes, multiple choice questions and viva voce type questions are given as a separate book, but free of cost. These questions are compiled from the question papers of various universities during the last decade. These questions will be ideal for students for last-minute preparation for examinations. We are introducing the online study material, which provides concepts of major topic as well as clinical case studies. This shall be updated through the year. Hence, students are advised to check the web page at regular intervals.

A textbook will be matured only by successive revisions. In the preface for the First edition, we expressed our desire to revise the textbook every 3 years. We were fortunate to keep that promise. This book has undergone metamorphosis during each edition. Chemical structures with computer technology were introduced in the Second edition. Color printing has been launched in the Third edition. The Fourth edition came out with multicolor printing. In the Fifth edition, the facts were presented in small paragraphs, so as to aid memory. In the Sixth edition, figures were drastically increased. In this Seventh edition, about 100 case studies are added. In this book, there are about 1100 figures, 230 tables and 200 boxes (perhaps we could call it as illustrated textbook of biochemistry), altogether making the book more student-friendly. The quality of paper is also improved during successive editions.

We were pleasantly surprised to receive many letters giving constructive criticisms and positive suggestions to improve the textbook. These responses were from all parts of the country (we got a few such letters from African and European students also). Such contributors include Heads of Departments, very senior professors, middle level teachers and mostly postgraduate students. We have tried to incorporate most of those suggestions, within the constraints of page limitations. In a way, this book thus became multi-authored, and truly national in character. This is to place on record, our deep gratitude for all those “pen-friends” who have helped us to improve this book. The first author desires more interaction with faculty and students who are using this textbook. All are welcome to communicate at his e-mail address <dmvasudevan@yahoo.co.in>

As indicated in the last edition, the first author is in the process of retirement, and would like to reduce the burden in due course. A successful textbook is something like a growing institution; individuals may come and go, but the institution will march ahead. Therefore, we felt the need to induce younger blood into the editorial board. Thus, a third author has been added in the Sixth edition, so that the torch can been handed over smoothly at an appropriate time later on. In this Seventh edition, the first author has taken less responsibility in editing the book, while the third author has taken more effort.

The help and assistance rendered by our postgraduate students in preparing this book are enormous. The official website of Nobel Academy has been used for pictures and biographies of Nobel laureates. Web pictures, without copyright protection, were also used in some figures. The remarkable success of the book was due to the active support of the publishers. This is to record our appreciation for the cooperation extended by Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Managing Director) and Mr Tarun Duneja (Director-Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India.

We hope that this Seventh edition will be friendlier to the students and be more attractive to the teachers. Now this is in your hands to judge.

 

“End of all knowledge must be building up of character”

—Mahatma Gandhi

                  DM Vasudevan

Sreekumari S

Kannan Vaidyanathan

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