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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