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《生物化学 Biochemistry》课程教学资源（课本材料）【美】Jeremy Berg, John Tymoczko, Lubert Stryer《Biochemistry（Seventh Edition）》

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ABOUT THE AUTHORS JEREMY M.BERG received his B.S.and M.S. Tymoczko received his B.A.from the University of degrees in Chemistry from Stanford(where he did Chicago in 1970 and his Ph.D.in Biochemistry from research with Keith Hodgson and Lubert Stryer)and the University of Chicago with Shutsung Liao at the his Ph.D.in Chemistry from Harvard with Richard Ben May Institute for Cancer Research.He then had Holm.He then completed a postdoctoral fellowship a postdoctoral position with Hewson Swift of the with Carl Pabo in Biophysics at Johns Hopkins Department of Biology at the University of Chicago. University School of Medicine.He was an Assistant The focus of his research has been on steroid Professor in the Department of Chemistry at Johns receptors,ribonucleoprotein particles,and Hopkins from 1986 to 1990.He then moved to Johns proteolytic processing enzymes. Hopkins University School of Medicine as Professor and Director of the Department of Biophysics and LUBERT STRYER is Winzer Professor of Cell Biophysical Chemistry,where he remained until 2003. Biology,Emeritus,in the School of Medicine and He then became Director of the National Institute of Professor of Neurobiology,Emeritus,at Stanford General Medical Sciences at the National Institutes University,where he has been on the faculty since of Health.He is an elected Fellow of the American 1976.He received his M.D.from Harvard Medical Association for the Advancement of Science and School.Professor Stryer has received many awards an elected member of the Institute of Medicine of for his research on the interplay of light and life, the National Academy of Sciences.He received the including the Eli Lilly Award for Fundamental American Chemical Society Award in Pure Chemistry Research in Biological Chemistry,the Distinguished (1994)and the Eli Lilly Award for Fundamental Inventors Award of the Intellectual Property Owners' Research in Biological Chemistry(1995),was named Association,and election to the National Academy of Maryland Outstanding Young Scientist of the Year Sciences and the American Philosophical Society.He (1995),received the Harrison Howe Award(1997), was awarded the National Medal of Science in 2006. the Distinguished Service Award from the Biophysical The publication of his first edition of Biochemistry in Society(2009),and the Howard K.Schachman 1975 transformed the teaching of biochemistry Public Service Award from the American Society for Biochemistry and Molecular Biology(2011).He also GREGORY J.GATTO,JR.,received his A.B.degree received numerous teaching awards,including the in Chemistry from Princeton University,where he W.Barry Wood Teaching Award(selected by medical worked with Martin F.Semmelhack and was awarded students),the Graduate Student Teaching Award,and the Everett S.Wallis Prize in Organic Chemistry.In the Professor's Teaching Award for the Preclinical 2003,he received his M.D.and Ph.D.degrees from the Sciences.He is coauthor,with Stephen J.Lippard,of Johns Hopkins University School of Medicine,where he the textbook Principles of Bioinorganic Chemistry. studied the structural biology of peroxisomal targeting signal recognition with Jeremy M.Berg and received the JOHN L.TYMOCZKO is Towsley Professor of Michael A.Shanoff Young Investigator Research Award. Biology at Carleton College,where he has taught He then completed a postdoctoral fellowship in 2006 since 1976.He currently teaches Biochemistry, with Christopher T.Walsh at Harvard Medical School, Biochemistry Laboratory,Oncogenes and the where he studied the biosynthesis of the macrolide Molecular Biology of Cancer,and Exercise immunosuppressants.He is currently an Investigator Biochemistry and coteaches an introductory course, in the Heart Failure Discovery Performance Unit at Energy Flow in Biological Systems.Professor GlaxoSmithKline Pharmaceuticals

i v JEREMY M. BERG received his B.S. and M.S. degrees in Chemistry from Stanford (where he did research with Keith Hodgson and Lubert Stryer) and his Ph.D. in Chemistry from Harvard with Richard Holm. He then completed a postdoctoral fellowship with Carl Pabo in Biophysics at Johns Hopkins University School of Medicine. He was an Assistant Professor in the Department of Chemistry at Johns Hopkins from 1986 to 1990. He then moved to Johns Hopkins University School of Medicine as Professor and Director of the Department of Biophysics and Biophysical Chemistry, where he remained until 2003. He then became Director of the National Institute of General Medical Sciences at the National Institutes of Health. He is an elected Fellow of the American Association for the Advancement of Science and an elected member of the Institute of Medicine of the National Academy of Sciences. He received the American Chemical Society Award in Pure Chemistry (1994) and the Eli Lilly Award for Fundamental Research in Biological Chemistry (1995), was named Maryland Outstanding Young Scientist of the Year (1995), received the Harrison Howe Award (1997), the Distinguished Service Award from the Biophysical Society (2009), and the Howard K. Schachman Public Service Award from the American Society for Biochemistry and Molecular Biology (2011). He also received numerous teaching awards, including the W. Barry Wood Teaching Award (selected by medical students), the Graduate Student Teaching Award, and the Professor’s Teaching Award for the Preclinical Sciences. He is coauthor, with Stephen J. Lippard, of the textbook Principles of Bioinorganic Chemistry. JOHN L. TYMOCZKO is Towsley Professor of Biology at Carleton College, where he has taught since 1976. He currently teaches Biochemistry, Biochemistry Laboratory, Oncogenes and the Molecular Biology of Cancer, and Exercise Biochemistry and coteaches an introductory course, Energy Flow in Biological Systems. Professor Tymoczko received his B.A. from the University of Chicago in 1970 and his Ph.D. in Biochemistry from the University of Chicago with Shutsung Liao at the Ben May Institute for Cancer Research. He then had a postdoctoral position with Hewson Swift of the Department of Biology at the University of Chicago. The focus of his research has been on steroid receptors, ribonucleoprotein particles, and proteolytic processing enzymes. LUBERT STRYER is Winzer Professor of Cell Biology, Emeritus, in the School of Medicine and Professor of Neurobiology, Emeritus, at Stanford University, where he has been on the faculty since 1976. He received his M.D. from Harvard Medical School. Professor Stryer has received many awards for his research on the interplay of light and life, including the Eli Lilly Award for Fundamental Research in Biological Chemistry, the Distinguished Inventors Award of the Intellectual Property Owners’ Association, and election to the National Academy of Sciences and the American Philosophical Society. He was awarded the National Medal of Science in 2006. The publication of his first edition of Biochemistry in 1975 transformed the teaching of biochemistry. GREGORY J. GATTO, JR., received his A.B. degree in Chemistry from Princeton University, where he worked with Martin F. Semmelhack and was awarded the Everett S. Wallis Prize in Organic Chemistry. In 2003, he received his M.D. and Ph.D. degrees from the Johns Hopkins University School of Medicine, where he studied the structural biology of peroxisomal targeting signal recognition with Jeremy M. Berg and received the Michael A. Shanoff Young Investigator Research Award. He then completed a postdoctoral fellowship in 2006 with Christopher T. Walsh at Harvard Medical School, where he studied the biosynthesis of the macrolide immunosuppressants. He is currently an Investigator in the Heart Failure Discovery Performance Unit at GlaxoSmithKline Pharmaceuticals. ABOUT THE AUTHORS

PREFACE n writing this seventh edition of Biochemistry,we we have greatly expanded our discussion of have balanced the desire to present up-to-the minute regulation and have split the chapter in the advances with the need to make biochemistry as clear preceding editions into two:Chapter 31,"The and engaging as possible for the student approaching Control of Gene Expression in Prokaryotes,"and the subject for the first time.Instructors and students Chapter 32,"The Control of Gene Expression have long relied on Biochemistry for: in Eukaryotes."These chapters address Clear writing The language of biochemistry is recent discoveries such as quorum sensing in made as accessible as possible.A straightforward prokaryotes,induced pluripotent stem cells, and logical organization leads the reader through and the role of microRNAs in regulating gene processes and helps navigate complex pathways expression. and mechanisms. Experimental techniques updated and Single-concept illustrations Illustrations in clarified We have revised Chapters 3("Exploring this book address one point at a time so that each Proteins and Proteomes"),5("Exploring Genes illustration clearly tells the story of a mechanism, and Genomes"),and 6("Exploring Evolution and pathway,or process without the distraction of Bioinformatics")to give students a practical excess detail. understanding of the benefits and limitations of the techniques that they will be using in the Physiological relevance Biochemistry is the laboratory.We have expanded explanations of study of life on the smallest scale,and it has always mass spectrometry and x-ray crystallography, been our goal to help students connect biochemistry for instance,and made them even clearer for the to their own lives.Pathways and processes are first-time student.We explain new techniques presented in a physiological context so that the such as next-generation sequencing and real-time reader can see how biochemistry works in different parts of the body and under different environmental PCR in the context of their importance to modern research in biochemistry.(For a full list, and hormonal conditions. see p.xii.) Clinical insights Wherever appropriate,pathways and mechanisms are applied to health and disease. These applications show students how biochemistry is relevant to them while reinforcing the concepts that Leptin they have just learned.(For a full list,see p.xi.) Eating Brain Evolutionary perspective Evolution is evident in the structures and pathways of biochemistry and is woven into the narrative of the textbook.(For a full list,see p.x.) New to This Edition Liver Intestine Glucose Researchers are making new discoveries in biochemistry every day.The seventh edition takes into account the discoveries that have changed how we think about the fundamental concepts in biochemistry and human health. Muscle New aspects of the book include: Fat Metabolism integrated in a new context New Insulin information about the role of leptins in hunger and satiety has greatly influenced how we think about obesity and the growing epidemic of diabetes.In this edition,we cover the integration of metabolism in the context of diet and obesity. Pancreas New chapters on gene regulation To relate Chapter 27 A schematic representation illustrates a few of the to the rapidly growing understanding of the many metabolic pathways that must be coordinated to meet the biochemical aspect of eukaryotic gene regulation demands of living

v I n writing this seventh edition of Biochemistry, we have balanced the desire to present up-to-the minute advances with the need to make biochemistry as clear and engaging as possible for the student approaching the subject for the first time. Instructors and students have long relied on Biochemistry for: • Clear writing The language of biochemistry is made as accessible as possible. A straightforward and logical organization leads the reader through processes and helps navigate complex pathways and mechanisms. • Single-concept illustrations Illustrations in this book address one point at a time so that each illustration clearly tells the story of a mechanism, pathway, or process without the distraction of excess detail. • Physiological relevance Biochemistry is the study of life on the smallest scale, and it has always been our goal to help students connect biochemistry to their own lives. Pathways and processes are presented in a physiological context so that the reader can see how biochemistry works in different parts of the body and under different environmental and hormonal conditions. • Clinical insights Wherever appropriate, pathways and mechanisms are applied to health and disease. These applications show students how biochemistry is relevant to them while reinforcing the concepts that they have just learned. (For a full list, see p. xi.) • Evolutionary perspective Evolution is evident in the structures and pathways of biochemistry and is woven into the narrative of the textbook. (For a full list, see p. x.) New to This Edition Researchers are making new discoveries in biochemistry every day. The seventh edition takes into account the discoveries that have changed how we think about the fundamental concepts in biochemistry and human health. New aspects of the book include: • Metabolism integrated in a new context New information about the role of leptins in hunger and satiety has greatly influenced how we think about obesity and the growing epidemic of diabetes. In this edition, we cover the integration of metabolism in the context of diet and obesity. • New chapters on gene regulation To relate to the rapidly growing understanding of the biochemical aspect of eukaryotic gene regulation, we have greatly expanded our discussion of regulation and have split the chapter in the preceding editions into two: Chapter 31, “The Control of Gene Expression in Prokaryotes,” and Chapter 32, “The Control of Gene Expression in Eukaryotes.” These chapters address recent discoveries such as quorum sensing in prokaryotes, induced pluripotent stem cells, and the role of microRNAs in regulating gene expression. • Experimental techniques updated and clarified We have revised Chapters 3 (“Exploring Proteins and Proteomes”), 5 (“Exploring Genes and Genomes”), and 6 (“Exploring Evolution and Bioinformatics”) to give students a practical understanding of the benefits and limitations of the techniques that they will be using in the laboratory. We have expanded explanations of mass spectrometry and x-ray crystallography, for instance, and made them even clearer for the first-time student. We explain new techniques such as next-generation sequencing and real-time PCR in the context of their importance to modern research in biochemistry. (For a full list, see p. xii.) Chapter 27 A schematic representation illustrates a few of the many metabolic pathways that must be coordinated to meet the demands of living. Brain Leptin Eating Liver Fat Intestine Muscle Insulin + Pancreas Glucose + – – PREFACE

vi Preface Recent Advances ( () Some of the exciting advances and new topics LAI LA2 that we present in the seventh edition include: LA3 Osteogenesis imperfecta,or brittle bone LA4 LDL disease(Chapter 2) LAS Intrinsically unstructured proteins and LA6 metamorphic proteins(Chapter 2) LA7 Recent updates in protein-misfolding EGFA diseases(Chapter 2) Endosome The use of recombinant DNA technology EGFB in protein purification(Chapter 3) Expanded discussion of mass spectrometry and x-ray crystallography(Chapter 3) Six-bladed Next-generation sequencing methods propeller (Chapter 5) structure Real-time PCR(Chapter 5) DNA microarrays(Chapter 5) Figure 26.24 LDL receptor releases LDL in the endosomes.[After I.D.Campbell, Carbon monoxide poisoning(Chapter 7) Biochem.Soc.Trans.31:1107-1114,2003,Fig 1A.] Single-molecule studies of enzyme kinetics (Chapter 8) Aromatase inhibitors in the treatment of breast and ovarian cancer(Chapter 26) Myosins as a model of a catalytic strategy for ATP hydrolysis(Chapter 9) The role of leptin in long-term caloric homeostasis (Chapter 27) Glycobiology and glycomics(Chapter 11) Obesity and diabetes(Chapter 27) Hurler disease(Chapter 11) Avian influenza H5N1(Chapter 11) Exercise and its effects on cellular biochemistry (Chapter 27) Lipid rafts(Chapter 12) Updated detailed mechanism of helicase's action Transferrin as an example of receptor-mediated (Chapter 28) endocytosis(Chapter 12) Updated detailed mechanism of topoisomerase's Long QT syndrome and arrhythmia caused by the action(Chapter 28) inhibition of potassium channels(Chapter 13) Riboswitches(Chapter 29) Defects in the citric acid cycle and the development The production of small regulatory RNAs(Chapter 29) of cancer(Chapter 17) Vanishing white matter disease(Chapter 30) Synthesizing a more efficient rubisco(Chapter 20) Quorum sensing(Chapter 31) The structure of mammalian fatty acid synthetase (Chapter 22) Biofilms(Chapter 31) Pyrimidine salvage pathways(Chapter 25) Induced pluripotent stem cells(Chapter 32) Physical association of enzymes in metabolic The role of microRNAs in gene regulation pathways(Chapter 25) (Chapter 32) Phosphatidic acid phosphatase in the regulation of How vaccines work (Chapter 34) lipid metabolism(Chapter 26) The structure of myosin head domains(Chapter 35) The regulation of SCAP-SREBP movement Cleaved segments of mRNA in cholesterol metabolism(Chapter 26) Mutations in the LDL receptor(Chapter 26) mRNA miRNA The role of HDL in protecting against Argonaute arteriosclerosis(Chapter 26) Figure 32.27 MicroRNA action

Recent Advances Some of the exciting advances and new topics that we present in the seventh edition include: • Osteogenesis imperfecta, or brittle bone disease (Chapter 2) • Intrinsically unstructured proteins and metamorphic proteins (Chapter 2) • Recent updates in protein-misfolding diseases (Chapter 2) • The use of recombinant DNA technology in protein purification (Chapter 3) • Expanded discussion of mass spectrometry and x-ray crystallography (Chapter 3) • Next-generation sequencing methods (Chapter 5) • Real-time PCR (Chapter 5) • DNA microarrays (Chapter 5) • Carbon monoxide poisoning (Chapter 7) • Single-molecule studies of enzyme kinetics (Chapter 8) • Myosins as a model of a catalytic strategy for ATP hydrolysis (Chapter 9) • Glycobiology and glycomics (Chapter 11) • Hurler disease (Chapter 11) • Avian influenza H5N1 (Chapter 11) • Lipid rafts (Chapter 12) • Transferrin as an example of receptor-mediated endocytosis (Chapter 12) • Long QT syndrome and arrhythmia caused by the inhibition of potassium channels (Chapter 13) • Defects in the citric acid cycle and the development of cancer (Chapter 17) • Synthesizing a more efficient rubisco (Chapter 20) • The structure of mammalian fatty acid synthetase (Chapter 22) • Pyrimidine salvage pathways (Chapter 25) • Physical association of enzymes in metabolic pathways (Chapter 25) • Phosphatidic acid phosphatase in the regulation of lipid metabolism (Chapter 26) • The regulation of SCAP-SREBP movement in cholesterol metabolism (Chapter 26) • Mutations in the LDL receptor (Chapter 26) • The role of HDL in protecting against arteriosclerosis (Chapter 26) • Aromatase inhibitors in the treatment of breast and ovarian cancer (Chapter 26) • The role of leptin in long-term caloric homeostasis (Chapter 27) • Obesity and diabetes (Chapter 27) • Exercise and its effects on cellular biochemistry (Chapter 27) • Updated detailed mechanism of helicase’s action (Chapter 28) • Updated detailed mechanism of topoisomerase’s action (Chapter 28) • Riboswitches (Chapter 29) • The production of small regulatory RNAs (Chapter 29) • Vanishing white matter disease (Chapter 30) • Quorum sensing (Chapter 31) • Biofilms (Chapter 31) • Induced pluripotent stem cells (Chapter 32) • The role of microRNAs in gene regulation (Chapter 32) • How vaccines work (Chapter 34) • The structure of myosin head domains (Chapter 35) vi Preface Figure 26.24 LDL receptor releases LDL in the endosomes. [After I. D. Campbell, Biochem. Soc. Trans. 31:1107 —1114, 2003, Fig 1A.] (A) (B) LA1 LA2 LDL LA3 LA4 LA5 LA6 LA7 EGFA EGFB Six-bladed propeller structure Endosome EGFC Cleaved segments of mRNA mRNA miRNA Argonaute Figure 32.27 MicroRNA action

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