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Harper's Illustrated Biochemistry, 28e Robert K. Murray, David A Bender, Kathleen M. Botham , Peter J. Kennelly, Victor W. Rodwell , P. Anthony Weil Preface Copyright Authors Chapter 1 Biochemistry & Medicine Chapter 2 Water & pH Section I. Structures & Functions of Proteins & Enzymes Chapter 3 Amino Acids & Peptides Chapter 4 Harper's Illustrated Biochemistry, 28e Robert K. Murray, David A Bender, Kathleen M. Botham , Peter J. Kennelly, Victor W. Rodwell , P. Anthony Weil Preface Copyright Authors Chapter 1 Biochemistry & Medicine Chapter 2 Water & pH Section I. Structures & Functions of Proteins & Enzymes Chapter 3 Amino Acids & Peptides Chapter 4 Proteins: Determination of Primary Structure Chapter 5 Proteins: Higher Orders of Structure Chapter 6 Proteins: Myoglobin & Hemoglobin Chapter 7 Enzymes: Mechanism of Action Chapter 8 Enzymes: Kinetics Chapter 9 Enzymes: Regulation of Activities Chapter 10 Bioinformatics & Computational Biology Section II. Bioenergetics & the Metabolism of Carbohydrates & Lipids Chapter 11 Bioenergetics: The Role of ATP Chapter 12 Biologic Oxidation Chapter 13 The Respiratory Chain & Oxidative Phosphorylation Chapter 14 Carbohydrates of Physiologic Significance Chapter 15 Lipids of Physiologic Significance Chapter 16 Overview of Metabolism & the Provision of Metabolic Fuels Chapter 17 The Citric Acid Cycle: The Catabolism of Acetyl-CoA Chapter 18 Glycolysis & the Oxidation of Pyruvate Chapter 19 Metabolism of Glycogen Chapter 20 Gluconeogenesis & the Control of Blood Glucose Chapter 21 The Pentose Phosphate Pathway & Other Pathways of Hexose Metabolism Chapter 22 Oxidation of Fatty Acids: Ketogenesis Chapter 23 Biosynthesis of Fatty Acids & Eicosanoids Chapter 24 Metabolism of Acylglycerols & Sphingolipids Chapter 25 Lipid Transport & Storage Chapter 26 Cholesterol Synthesis, Transport, & Excretion Section III. Metabolism of Proteins & Amino Acids Chapter 27 Biosynthesis of the Nutritionally Nonessential Amino Acids Chapter 28 Catabolism of Proteins & of Amino Acid Nitrogen Chapter 29 Catabolism of the Carbon Skeletons of Amino Acids Chapter 30 Conversion of Amino Acids to Specialized Products Chapter 31 Porphyrins & Bile Pigments Section IV. Structure, Function, & Replication of Informational Macromolecules Chapter 32 Nucleotides Chapter 33 Metabolism of Purine & Pyrimidine Nucleotides Chapter 34 Nucleic Acid Structure & Function Chapter 35 DNA Organization, Replication, & Repair Chapter 36 RNA Synthesis, Processing, & Modification Chapter 37 Protein Synthesis & the Genetic Code Chapter 38 Regulation of Gene Expression Chapter 39 Molecular Genetics, Recombinant DNA, & Genomic Technology Section V. Biochemistry of Extracellular & Intracellular Communication Chapter 40 Membranes: Structure & Function Chapter 41 The Diversity of the Endocrine System Chapter 42 Hormone Action & Signal Transduction Section VI. Special Topics Chapter 43 Nutrition, Digestion, & Absorption Chapter 44 Micronutrients: Vitamins & Minerals Chapter 45 Free Radicals and Antioxidant Nutrients Chapter 46 Intracellular Traffic & Sorting of Proteins Chapter 47 Glycoproteins Chapter 48 The Extracellular Matrix Chapter 49 Muscle & the Cytoskeleton Chapter 50 Plasma Proteins & Immunoglobulins Chapter 51 Hemostasis & Thrombosis Chapter 52 Red & White Blood Cells Chapter 53 Metabolism of Xenobiotics Chapter 54 Biochemical Case Histories Appendix I Appendix II Close Window Copyright Information Harper's Illustrated Biochemistry, Twenty-Eighth Edition Copyright © 2009 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in China. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher. Previous editions copyright © 2006, 2003 by The McGraw-Hill Companies, Inc.; 2000, 1996, 1993, 1990 by Appleton & Lange; copyright © 1988 by Lange Medical Publications. ISBN 978-0-07-162591-3 Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. Close Window Authors Robert K. Murray, MD, PhD Professor (Emeritus) of Biochemistry University of Toronto Toronto, Ontario David A. Bender, PhD Sub-Dean University College Medical School Senior Lecturer in Biochemistry Department of Structural and Molecular Biology and Division of Medical Education University College London Kathleen M. Botham, PhD, DSc Professor of Biochemistry Royal Veterinary College University of London Peter J. Kennelly, PhD Professor and Head Department of Biochemistry Virginia Polytechnic Institute and State University Blacksburg, Virginia Victor W. Rodwell, PhD Emeritus Professor of Biochemistry Purdue University West Lafayette, Indiana P. Anthony Weil, PhD Professor of Molecular Physiology and Biophysics Vanderbilt University School of Medicine Nashville, Tennessee Co-Authors Daryl K. Granner, MD Emeritus Professor of Molecular Physiology and Biophysics and Medicine, Vanderbilt University, Nashville, Tennessee Peter L. Gross, MD, MSc, FRCP(C) Associate Professor, Department of Medicine, McMaster University, Hamilton, Ontario Frederick W. Keeley, PhD Associate Director and Senior Scientist, Research Institute, Hospital for Sick Children, Toronto, and Professor, Department of Biochemistry, University of Toronto, Toronto, Ontario Peter A. Mayes, PhD, DSc Emeritus Professor of Veterinary Biochemistry, Royal Veterinary College, University of London, London Margaret L. Rand, PhD Associate Senior Scientist, Hospital for Sick Children, Toronto, and Professor, Departments of Laboratory Medicine & Pathobiology and Biochemistry, University of Toronto, Toronto, Ontario Close Window Preface The authors and publisher are pleased to present the twentyeighth edition of Harper's Illustrated Biochemistry. This edition features for the first time multiple color images, many entirely new, that vividly emphasize the ever-increasing complexity of biochemical knowledge. The cover picture of green fluorescent protein (GFP), which recognizes the award of the 2008 Nobel Prize in Chemistry to Martin Chalfie, Roger Y. Tsien, and Osamu Shimomura, reflects the book's emphasis on new developments. Together with its derivatives, GFP fulfills an ever-widening role in tracking protein movement in intact cells and tissues, and has multiple applications to cell biology, biochemistry and medicine. In this edition, we bid a regretful farewell to long-time author and editor, Daryl Granner. In 1983, in preparation for the 20th edition, Daryl was asked to write new chapters on the endocrine system and the molecular mechanism of hormones, which he did with great success. He assumed responsibility for the chapters on membranes, protein synthesis and molecular biology in the 21st edition, and wrote a highly informative new chapter on the then emerging field of recombinant DNA technology. Over the ensuing 25 years, through the 27th edition, Daryl continuously revised his chapters to provide concise, instructive descriptions of these rapidly changing, complex fields. Daryl's editorial colleagues express their gratitude for his many invaluable contributions as an author, editor and a friend, and wish him all the best in his future endeavors. David Bender, Kathleen Botham, Peter Kennelly, and Anthony Weil, formerly co-authors, are now full authors. Rob Murray gratefully acknowledges the major contributions of Peter Gross, Fred Keeley, and Margaret Rand to specific chapters, and thanks Reinhart Reithmeier, Alan Volchuk, and David B. Williams for reviewing and making invaluable suggestions for the revision of Chapters 40 and 46. In addition, he is grateful to Kasra Haghighat and Mohammad Rassouli-Rashti for reading and suggesting improvements to Chapter 54. Changes in the Twenty-Eighth Edition Consistent with our goal of providing students with a text that describes and illustrates biochemistry in a comprehensive, concise, and readily accessible manner, the authors have incorporated substantial new material in this edition. Many new figures and tables have been added. Every chapter has been revised, updated and in several instances substantially rewritten to incorporate the latest advances in both knowledge and technology of importance to the understanding and practice of medicine. Two new chapters have been added. Chapter 45, entitled “Free Radicals and Antioxidant Nutrients,” describes the sources of free radicals; their damaging effects on DNA, proteins, and lipids; and their roles in causing diseases such as cancer and atherosclerosis. The role of antioxidants in counteracting their deleterious effects is assessed. Chapter 54, entitled “Biochemical Case Histories,” provides extensive presentations of 16 pathophysiologic conditions: adenosine deaminase deficiency, Alzheimer disease, cholera, colorectal cancer, cystic fibrosis, diabetic ketoacidosis, Duchenne muscular dystrophy, ethanol intoxication, gout, hereditary hemochromatosis, hypothyroidism, kwashiorkor (and protein-energy malnutrition), myocardial infarction, obesity, osteoporosis, and xeroderma pigmentosum. Important new features of medical interest include: Influence of the Human Genome Project on various biomedical fields. Re-write of the use of enzymes in medical diagnosis. New material on computer-aided drug discovery. Compilation of some conformational diseases. New material on advanced glycation end-products and their importance in diabetes mellitus. New material on the attachment of influenza virus to human cells. Some major challenges facing medicine. The following topics that have been added to various chapters are of basic biochemical interest: Expanded coverage of mass spectrometry, a key analytical method in contemporary biochemistry. New figures revealing various aspects of protein structure. Expanded coverage of active sites of enzymes and transition states. New information on methods of assaying enzymes. Expanded coverage of aspects of enzyme kinetics. New information on micro- and silencing RNAs. New information on eukaryotic transcription mechanisms, including the biogenesis of mRNA and the role of nucleosomes. Description of activities of miRNAs. New material on Next Generation Sequencing (NGS) platforms. New material on the Chromatin Immunoprecipitation (CHIP) technology and its uses. New information on subcellular localization of key signaling enzymes (kinases, phosphatases). New information on how hormones affect gene transcription. Every chapter begins with a summary of the biomedical importance of its contents and concludes with a summary reviewing the major topics covered. Organization of the Book Following two introductory chapters (“Biochemistry and Medicine” and “Water and pH”), the text is divided into six main sections. All sections and chapters emphasize the medical relevance of biochemistry. Section I addresses the structures and functions of proteins and enzymes. Because almost all of the reactions in cells are catalyzed by enzymes, it is vital to understand the properties of enzymes before considering other topics. This section also contains a chapter on bioinformatics and computational biology, reflecting the increasing importance of these topics in modern biochemistry, biology and medicine. Section II explains how various cellular reactions either utilize or release energy, and traces the pathways by which carbohydrates and lipids are synthesized and degraded. Also described are the many functions of these two classes of molecules. Section III deals with the amino acids, their many metabolic fates, certain key features of protein catabolism, and the biochemistry of the porphyrins and bile pigments. Section IV describes the structures and functions of the nucleotides and nucleic acids, and includes topics such as DNA replication and repair, RNA synthesis and modification, protein synthesis, the principles of recombinant DNA and genomic technology, and new understanding of how gene expression is regulated. Section V deals with aspects of extracellular and intracellular communication. Topics include membrane structure and function, the molecular bases of the actions of hormones, and the key field of signal transduction. Section VI discusses twelve special topics: nutrition, digestion and absorption; vitamins and minerals; free radicals and antioxidants; intracellular trafficking and sorting of proteins; glycoproteins; the extracellular matrix; muscle and the cytoskeleton; plasma proteins and immunoglobulins; hemostasis and thrombosis; red and white blood cells; the metabolism of xenobiotics; and 16 biochemically oriented case histories. The latter chapter concludes with a brief Epilog indicating some major challenges for medicine in whose solution biochemistry and related disciplines will play key roles. Appendix I contains a list of laboratory results relevant to the cases discussed in Chapter 54. Appendix II contains a list of useful web sites and a list of biochemical journals or journals with considerable biochemical content. Acknowledgments The authors thank Michael Weitz for his vital role in the planning and actualization of this edition. It has been a pleasure to work with him. We are also very grateful to Kim Davis for her highly professional supervising of the editing of the text, to Sherri Souffrance for supervising its production, to Elise Langdon for its design, and to Margaret Webster-Shapiro for her work on the cover art. We warmly acknowledge the work of the artists, typesetters, and other individuals not known to us who participated in the production of the twenty-eighth edition of Harper's Illustrated Biochemistry. In particular, we are very grateful to Joanne Jay of Newgen North America for her central role in the management of the entire project and to Joseph Varghese of Thomson Digital for his skilled supervision of the large amount of art work that was necessary for this edition. Suggestions from students and colleagues around the world have been most helpful in the formulation of this edition. We look forward to receiving similar input in the future. Robert K. Murray, Toronto, Ontario, Canada David A. Bender, London, UK Kathleen M. Botham, London, UK Peter J. Kennelly, Blacksburg, Virginia, USA Victor W. Rodwell, West Lafayette, Indiana, USA P. Anthony Weil, Nashville, Tennessee, USA Print Close Window Note: Large images and tables on this page may necessitate printing in landscape mode. Copyright © The McGraw-Hill Companies. All rights reserved. Harper's Illustrated Biochemistry, 28e > Chapter 1. Biochemistry & Medicine > BIOCHEMISTRY & MEDICINE: INTRODUCTION Biochemistry can be defined as the science of the chemical basis of life (Gk bios "life"). The cell is the structural unit of living systems. Thus, biochemistry can also be described as the science of the chemical constituents of living cells and of the reactions and processes they undergo. By this definition, biochemistry encompasses large areas of cell biology, molecular biology, and molecular genetics. The Aim of Biochemistry Is to Describe & Explain, in Molecular Terms, All Chemical Processes of Living Cells The major objective of biochemistry is the complete understanding, at the molecular level, of all of the chemical processes associated with living cells. To achieve this objective, biochemists have sought to isolate the numerous molecules found in cells, determine their structures, and analyze how they function. Many techniques have been used for these purposes; some of them are summarized in Table 1–1. Table 1–1. The Principal Methods and Preparations Used in Biochemical Laboratories Methods for Separating and Purifying Biomolecules1 Salt fractionation (eg, precipitation of proteins with ammonium sulfate) Chromatography: Paper, ion exchange, affinity, thin-layer, gas–liquid, high-pressure liquid, gel filtration Electrophoresis: Paper, high-voltage, agarose, cellulose acetate, starch gel, polyacrylamide gel, SDS- polyacrylamide gel Ultracentrifugation Methods for Determining Biomolecular Structures Elemental analysis UV, visible, infrared, and NMR spectroscopy Use of acid or alkaline hydrolysis to degrade the biomolecule under study into its basic constituents Use of a battery of enzymes of known specificity to degrade the biomolecule under study (eg, proteases, nucleases, glycosidases) Mass spectrometry Specific sequencing methods (eg, for proteins and nucleic acids) X-ray crystallography Preparations for Studying Biochemical Processes Whole animal (includes transgenic animals and animals with gene knockouts) Isolated perfused organ Tissue slice Whole cells Homogenate Isolated cell organelles Subfractionation of organelles Purified metabolites and enzymes Isolated genes (including polymerase chain reaction and site-directed mutagenesis) 1Most of these methods are suitable for analyzing the components present in cell homogenates and other biochemical preparations. The sequential use of several techniques will generally permit purification of most biomolecules. The reader is referred to texts on methods of biochemical research for details. A Knowledge of Biochemistry Is Essential to All Life Sciences The biochemistry of the nucleic acids lies at the heart of genetics; in turn, the use of genetic approaches has been critical for elucidating many areas of biochemistry. Physiology, the study of body function, overlaps with biochemistry almost completely. Immunology employs numerous biochemical techniques, and many immunologic approaches have found wide use by biochemists. Pharmacology and pharmacy rest on a sound knowledge of biochemistry and physiology; in particular, most drugs are metabolized by enzyme-catalyzed reactions. Poisons act on biochemical reactions or processes; this is the subject matter of toxicology. Biochemical approaches are being used increasingly to study basic aspects of pathology (the study of disease), such as inflammation, cell injury, and cancer. Many workers in microbiology, zoology, and botany employ biochemical approaches almost exclusively. These relationships are not surprising, because life as we know it depends on biochemical reactions and processes. In fact, the old barriers among the life sciences are breaking down, and biochemistry is increasingly becoming their common language. A Reciprocal Relationship Between Biochemistry & Medicine Has Stimulated Mutual Advances The two major concerns for workers in the health sciences—and particularly physicians—are the understanding and maintenance of health and the understanding and effective treatment of diseases. Biochemistry impacts enormously on both of these fundamental concerns of medicine. In fact, the interrelationship of biochemistry and medicine is a wide, two-way street. Biochemical studies have illuminated many aspects of health and disease, and conversely, the study of various aspects of health and disease has opened up new areas of biochemistry. Some examples of this two-way street are shown in Figure 1–1. For instance, knowledge of protein structure and function was necessary to elucidate the single biochemical difference between normal hemoglobin and sickle cell hemoglobin. On the other hand, analysis of sickle cell hemoglobin has contributed significantly to our understanding of the structure and function of both normal hemoglobin and other proteins. Analogous examples of reciprocal benefit between biochemistry and medicine could be cited for the other paired items shown in Figure 1–1. Another example is the pioneering work of Archibald Garrod, a physician in England during the early 1900s. He studied patients with a number of relatively rare disorders (alkaptonuria, albinism, cystinuria, and pentosuria; these are described in later chapters) and established that these conditions were genetically determined. Garrod designated these conditions as inborn errors of metabolism. His insights provided a major foundation for the development of the field of human biochemical genetics. More recent efforts to understand the basis of the genetic disease known as familial hypercholesterolemia, which results in severe atherosclerosis at an early age, have led to dramatic progress in understanding of cell receptors and of mechanisms of uptake of cholesterol into cells. Studies of oncogenes in cancer cells have directed attention to the molecular mechanisms involved in the control of normal cell growth. These and many other examples emphasize how the study of disease can open up areas of cell function for basic biochemical research. Figure 1–1. Examples of the two-way street connecting biochemistry and medicine. Knowledge of the biochemical molecules shown in the top part of the diagram has clarified our understanding of the diseases shown on the bottom half—and conversely, analyses of the diseases shown below have cast light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease and that both atherosclerosis and diabetes mellitus have genetic components. The relationship between medicine and biochemistry has important implications for the former. As long as medical treatment is firmly grounded in the knowledge of biochemistry and other basic sciences, the practice of medicine will have a rational basis that can be adapted to accommodate new knowledge. This contrasts with unorthodox health cults and at least some "alternative medicine" practices that are often founded on little more than myth and wishful thinking and generally lack any intellectual basis. NORMAL BIOCHEMICAL PROCESSES ARE THE BASIS OF HEALTH The World Health Organization (WHO) defines health as a state of "complete physical, mental and social well-being and not merely the absence of disease and infirmity." From a strictly biochemical viewpoint, health may be considered that situation in which all of the many thousands of intra- and extracellular reactions that occur in the body are proceeding at rates commensurate with the organism's maximal survival in the physiologic state. However, this is an extremely reductionist view, and it should be apparent that caring for the health of patients requires not only a wide knowledge of biologic principles but also of psychologic and social principles.

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Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.