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G R V d e t i n U vip.persianss.ir A LANGE medical book Illustrated Harper’s Biochemistry G T h i r T i e T h Re d i T i o n V d Victor W. Rodwell, PhD Peter J. Kennelly, PhD e Professor (Emeritus) of Biochemistry Professor and Head Purdue University Department of Biochemistry t West Lafayette, Indiana Virginia Tech i Blacksburg, Virginia n David A. Bender, PhD P. Anthony Weil, PhD Professor (Emeritus) of Nutritional Biochemsitry U University College London Professor London, United Kingdom Department of Molecular Physiology & Biophysics Vanderbilt University Kathleen M. Botham, PhD, DSc Nashville, Tennessee Emeritus Professor of Biochemistry Department of Comparative Biomedical Sciences Royal Veterinary College University of London London, United Kingdom new York Chicago San Francisco Athens London Madrid Mexico City Milan new delhi Singapore Sydney Toronto vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 1 03/11/14 4:58 PM Copyright © 2015 by The McGraw-Hill Education. All rights reserved. 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THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USIdNG THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its opereation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation t of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. i n U vip.persianss.ir Co-Authors Peter L. Gross, MD, MSc, FRCP(C) Robert K. Murray, MD, PhD Associate Professor Emeritus Professor of Biochemistry Department of Medicine University of Toronto McMaster University Toronto, Ontario Hamilton, Ontario, Canada Margaret L. Rand, PhD Molly Jacob, MBBS, MD, PhD Senior Associate Scientist Professor and Chair The Hospital for Sick ChildGren Toronto, and Professor Department of Biochemistry Department of Laboratory Medicine & Pathobiology Christian Medical College University of Toronto, Toronto, Canada Vellore, Tamil Nadu, India R Joe Varghese, MBBS, MD, DNB Peter A. Mayes, PhD, DSc Emeritus Professor of Veterinary Biochemistry AssociatVe Professor Department of Biochemistry Royal Veterinary College Christian Medical College University of London dVellore, Tamil Nadu London, United Kingdom e t i n U iii vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 3 03/11/14 4:58 PM G R V d e t i n U vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 4 03/11/14 4:58 PM G R V d e t i n U vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 5 03/11/14 4:58 PM G R V d e This page intentionally left blank t i n U vip.persianss.ir Contents Preface xi 10 Bioinformatics & Computational S e C T i o n Structures & Functions of Biology 97 I Proteins & Enzymes 1 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD G 1 Biochemistry & Medicine 1 S e C T i o n Victor W. Rodwell, PhD & Robert K. Murray, MD, PhD III Bioenergetics 113 R 2 Water & ph 6 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD V 11 Bioenergetics: The role of ATP 113 3 Amino Acids & Peptides 15 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc Peter J. Kennelly, PhD & Victor W. Rodwell, PhD d 12 Biologic oxidation 119 4 Proteins: determination of Primary e Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc Structure 25 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD t 13 The respiratory Chain & oxidative i Phosphorylation 126 5 Proteins: higher orders of Strucnture 36 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc Peter J. Kennelly, PhD & Victor W. Rodwell, PhD U S e C T i o n Metabolism of S e C T i o n Enzymes: Kinetics, IV Carbohydrates 139 II Mechanism, Regulation, & Bioinformatics 51 14 overview of Metabolism & the Provision 6 Proteins: Myoglobin & hemoglobin 51 of Metabolic Fuels 139 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD David A. Bender, PhD & Peter A. Mayes, PhD, DSc 7 enzymes: Mechanism of Action 60 15 Carbohydrates of Physiological Peter J. Kennelly, PhD & Victor W. Rodwell, PhD Significance 152 David A. Bender, PhD & Peter A. Mayes, PhD, DSc 8 enzymes: Kinetics 73 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD 16 The Citric Acid Cycle: The Central Pathway of Carbohydrate, Lipid & Amino Acid 9 enzymes: regulation of Activities 87 Metabolism 161 Peter J. Kennelly, PhD & Victor W. Rodwell, PhD David A. Bender, PhD & Peter A. Mayes, PhD, DSc vii vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 7 03/11/14 4:58 PM viii CONTENTS 17 Glycolysis & the Oxidation of Pyruvate 168 28 Catabolism of Proteins & of Amino Acid David A. Bender, PhD & Peter A. Mayes, PhD, DSc Nitrogen 287 Victor W. Rodwell, PhD 18 Metabolism of Glycogen 176 David A. Bender, PhD & Peter A. Mayes, PhD, DSc 29 Catabolism of the Carbon Skeletons of Amino Acids 297 19 Gluconeogenesis & the Control of Blood Victor W. Rodwell, PhD Glucose 185 David A. Bender, PhD & Peter A. Mayes, PhD, DSc 30 Conversion of Amino Acids to Specialized Products 313 20 The Pentose Phosphate Pathway & Other Victor W. Rodwell, PhD Pathways of Hexose Metabolism 196 David A. Bender, PhD & Peter A. Mayes, PhD, DSc 31 Porphyrins & Bile Pigments 323 G Victor W. Rodwell, PhD & Robert K. Murray, MD, PhD S E C T I O N V Metabolism of Lipids 211 R S E C T I O N Structure, Function, & VVII Replication of Informational 21 Lipids of Physiologic Significance 211 Macromolecules 339 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc d 32 Nucleotides 339 22 Oxidation of Fatty Acids: Ketogenesis 223 e Victor W. Rodwell, PhD Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc 33 Metabolism of Purine & Pyrimidine t 23 Biosynthesis of Fatty Nucleotides 347 i Acids & Eicosanoids 232 n Victor W. Rodwell, PhD Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc U 34 Nucleic Acid Structure & Function 359 24 Metabolism of Acylglycerols P. Anthony Weil, PhD & Sphingolipids 245 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc 35 DNA Organization, Replication, & Repair 370 25 Lipid Transport & Storage 253 P. Anthony Weil, PhD Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc 36 RNA Synthesis, Processing, 26 Cholesterol Synthesis, Transport, & Modification 394 & Excretion 266 P. Anthony Weil, PhD Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc 37 Protein Synthesis & the Genetic Code 413 P. Anthony Weil, PhD S E C T I O N Metabolism of Proteins VI 38 Regulation of Gene Expression 428 & Amino Acids 281 P. Anthony Weil, PhD 27 Biosynthesis of the Nutritionally 39 Molecular Genetics, Recombinant DNA, Nonessential Amino Acids 281 & Genomic Technology 451 Victor W. Rodwell, PhD P. Anthony Weil, PhD vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 8 05/11/14 4:35 PM CONTENTS ix S E C T I O N Biochemistry of S E C T I O N VIII Extracellular & Intracellular X Special Topics (B) 607 Communication 477 40 Membranes: Structure 49 Intracellular Traffic & Sorting of Proteins 607 & Function 477 Kathleen M. Botham , PhD, DSc & Robert K. Murray, MD, PhD Robert K. Murray, MD, PhD & P. Anthony Weil, PhD 50 The Extracellular Matrix 627 41 The Diversity of the Endocrine Kathleen M. Botham, PhD, DSc & Robert K. Murray, MD, PhD System 498 P. Anthony Weil, PhD 51 Muscle & the Cytoskeleton 647 Peter J. Kennelly, PhD & Robert K. Murray, MD, PhD G 42 Hormone Action & Signal Transduction 518 52 Plasma Proteins & Immunoglobulins 668 P. Anthony Weil, PhD Peter J. Kennelly, PhD, Robert K. Murray, MD, PhD, Molly R Jacob, MBBS, MD, PhD & Joe Varghese, MBBS, MD 53 Red Blood Cells 689 V Peter J. Kennelly, PhD & Robert K. Murray, MD, PhD S E C T I O N IX Special Topics (A) 537 d 54 White Blood Cells 700 Peter J. Kennelly, PhD & Robert K. Murray, MD, PhD e 43 Nutrition, Digestion, & Absorption 537 t S E C T I O N David A. Bender, PhD & Peter A. Mayes , PhD, DiSc XI Special Topics (C) 711 n 44 Micronutrients: Vitamins U & Minerals 546 David A. Bender, PhD 55 Hemostasis & Thrombosis 711 Peter L. Gross, MD, MSc, FRCP(C), Robert K. Murray, MD, PhD, P. Anthony Weil, PhD, & Margaret L. Rand, PhD 45 Free Radicals & Antioxidant Nutrients 564 56 Cancer: An Overview 722 David A. Bender, PhD Molly Jacob, MBBS, MD, PhD, Joe Varghese, MBBS, MD, Robert K. Murray, MD, PhD & P. Anthony Weil, PhD 46 Glycoproteins 569 David A. Bender, PhD & Robert K. Murray, MD, PhD 57 Biochemical Case Histories 746 David A. Bender, PhD 47 Metabolism of Xenobiotics 583 David A. Bender, PhD & Robert K. Murray, MD, PhD 58 The Biochemistry of Aging 755 Peter J. Kennelly, PhD 48 Clinical Biochemistry 589 David A. Bender, PhD, Joe Varghese, MBBS, MD, The Answer Bank 771 Molly Jacob, MBBS, MD, PhD, & Robert K. Murray, MD, PhD Index 777 vip.persianss.ir 00_Rodwell_FM_pi-xii.indd 9 07/11/14 6:36 PM

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