《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）》.pdf_大学文库

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

Preface vii New End-of-Chapter Problems Figure legends direct students explicitly to the key features of a model. Biochemistry is best learned by practicing it and,to help students practice biochemistry,we have increased A great variety of types of molecular structures the number of end-of-chapter problems by 50%.In are represented,including clearer renderings of addition to many traditional problems that test bio- membrane proteins. chemical knowledge and the ability to use this knowl- For most molecular models,the PDB number at edge,we have three categories of problems to address the end of the figure legend gives the reader easy specific problem-solving skills access to the file used in generating the structure Mechanism problems ask students to suggest or from the Protein Data Bank Web site(www.pdb. elaborate a chemical mechanism. org).At this site,a variety of tools for visualizing Data interpretation problems ask questions about and analyzing the structure are available a set of data provided in tabulated or graphic form. Living figures for most molecular structures now These problems give students a sense of how appear on the Web site in Jmol to allow students scientific conclusions are reached to rotate three-dimensional molecules and view Chapter integration problems require students alternative renderings online. to use information from several chapters to reach a solution.These problems reinforce a student's awareness of the interconnectedness of the different AMP-PNP aspects of biochemistry. Brief solutions to these problems are presented at the end of the book;expanded solutions are available in the accompanying Student Companion. Visualizing Molecular Structure All molecular structures have been selected and ren- dered by Jeremy Berg and Gregory Gatto.To help stu- 15 dents read and understand these structures,we include the following tools: ·A molecular-model“primer'”explains the different Figure 28.12 Helicase asymmetry.Notice that only four of the types of protein models and examines their strengths subunits,those shown in blue and yellow,bind AMP-PNP.[Drawn from and weaknesses(see appendices to Chapters 1 and 2). 1EOK.pdb.]

Preface vii New End-of-Chapter Problems Biochemistry is best learned by practicing it and, to help students practice biochemistry, we have increased the number of end-of-chapter problems by 50%. In addition to many traditional problems that test biochemical knowledge and the ability to use this knowledge, we have three categories of problems to address specific problem-solving skills. • Mechanism problems ask students to suggest or elaborate a chemical mechanism. • Data interpretation problems ask questions about a set of data provided in tabulated or graphic form. These problems give students a sense of how scientific conclusions are reached. • Chapter integration problems require students to use information from several chapters to reach a solution. These problems reinforce a student’s awareness of the interconnectedness of the different aspects of biochemistry. Brief solutions to these problems are presented at the end of the book; expanded solutions are available in the accompanying Student Companion. Visualizing Molecular Structure All molecular structures have been selected and rendered by Jeremy Berg and Gregory Gatto. To help students read and understand these structures, we include the following tools: • A molecular-model “primer” explains the different types of protein models and examines their strengths and weaknesses (see appendices to Chapters 1 and 2). • Figure legends direct students explicitly to the key features of a model. • A great variety of types of molecular structures are represented, including clearer renderings of membrane proteins. • For most molecular models, the PDB number at the end of the figure legend gives the reader easy access to the file used in generating the structure from the Protein Data Bank Web site (www.pdb. org). At this site, a variety of tools for visualizing and analyzing the structure are available. • Living figures for most molecular structures now appear on the Web site in Jmol to allow students to rotate three-dimensional molecules and view alternative renderings online. Figure 28.12 Helicase asymmetry. Notice that only four of the subunits, those shown in blue and yellow, bind AMP-PNP. [Drawn from 1E0K.pdb.] 0° 0° 30° 30° 15° 15° AMP-PNP

Media and Supplements A full package of media resources and supplements provides instructors and students with innovative tools to support a variety of teaching and learning approaches. eBook http://ebooks.bfwpub.com/berg7e BIOCHEMP☏RTAL This online version of the textbook combines the con- http://courses.bfwpub.com/berg7e tents of the printed book,electronic study tools,and BiochemPortal is a dynamic,fully integrated learning a full complement of student media specifically cre- environment that brings together all of our teaching ated to support the text.Problems and resources from and learning resources in one place.It features easy- the printed textbook are incorporated throughout the to-use assessment tracking and grading tools that eBook,to ensure that students can easily review specific enable instructors to assign problems for practice,as concepts.The eBook enables students to: homework,quizzes,or tests.A personalized calendar, Access the complete book and its electronic study an announcement center,and communication tools tools from any internet-connected computer by help instructors manage the course.In addition to using a standard Web browser; all the resources found on the Companion Web site, BiochemPortal includes several other features: Navigate quickly to any section or subsection of the book or any page number of the printed book; The interactive eBook integrates the complete text Add their own bookmarks,notes,and highlighting; with all relevant media resources. Access all the fully integrated media resources asso- Hundreds of self-graded practice problems ciated with the book; allow students to test their understanding of Review quizzes and personal notes to help prepare concepts explained in the text,with immediate feedback for exams;and Search the entire eBook instantly,including the The metabolic map helps students understand index and spoken glossary. the principles and applications of the core metabolic Instructors teaching from the eBook can assign either pathways.Students can work through guided the entire textbook or a custom version that includes tutorials with embedded assessment questions,or only the chapters that correspond to their syllabi.They explore the Metabolic Map on their own using the can choose to add notes to any page of the eBook and dragging and zooming functionality of the map. share these notes with their students.These notes may Jmol tutorials by Jeffrey Cohlberg,California State include text,Web links,animations,or photographs. University at Long Beach,teach students how to create models of proteins in Jmol based on data from the Protein Database.By working through the tutorial BiochemPortal and answering assessment questions at BIOCHEMP ORTAL Biochemistry vemeoN BERG·TYMOCZKO·STRYER the end of each exercise,students learn to use this important database and BiochemPortal(Berg 7e) fully realize the relationship between ●Course Info BiochemPortal QuickStart structure and function of enzymes. ·o略2 Animated techniques illustrate Assignments laboratory techniques described in ·ma出 ndk thoom chorhes前 the text. Gradebook Announcements Concept tutorials walk students through complex ideas in enzyme ⑦Communicate kinetics and metabolism. viii

viii eBook http://ebooks.bfwpub.com/berg7e This online version of the textbook combines the contents of the printed book, electronic study tools, and a full complement of student media specifically created to support the text. Problems and resources from the printed textbook are incorporated throughout the eBook, to ensure that students can easily review specific concepts. The eBook enables students to: • Access the complete book and its electronic study tools from any internet-connected computer by using a standard Web browser; • Navigate quickly to any section or subsection of the book or any page number of the printed book; • Add their own bookmarks, notes, and highlighting; • Access all the fully integrated media resources associated with the book; • Review quizzes and personal notes to help prepare for exams; and • Search the entire eBook instantly, including the index and spoken glossary. Instructors teaching from the eBook can assign either the entire textbook or a custom version that includes only the chapters that correspond to their syllabi. They can choose to add notes to any page of the eBook and share these notes with their students. These notes may include text, Web links, animations, or photographs. http://courses.bfwpub.com/berg7e BiochemPortal is a dynamic, fully integrated learning environment that brings together all of our teaching and learning resources in one place. It features easyto-use assessment tracking and grading tools that enable instructors to assign problems for practice, as homework, quizzes, or tests. A personalized calendar, an announcement center, and communication tools help instructors manage the course. In addition to all the resources found on the Companion Web site, BiochemPortal includes several other features: • The interactive eBook integrates the complete text with all relevant media resources. • Hundreds of self-graded practice problems allow students to test their understanding of concepts explained in the text, with immediate feedback. • The metabolic map helps students understand the principles and applications of the core metabolic pathways. Students can work through guided tutorials with embedded assessment questions, or explore the Metabolic Map on their own using the dragging and zooming functionality of the map. • Jmol tutorials by Jeffrey Cohlberg, California State University at Long Beach, teach students how to create models of proteins in Jmol based on data from the Protein Database. By working through the tutorial and answering assessment questions at the end of each exercise, students learn to use this important database and fully realize the relationship between structure and function of enzymes. • Animated techniques illustrate laboratory techniques described in the text. • Concept tutorials walk students through complex ideas in enzyme kinetics and metabolism. Media and Supplements A full package of media resources and supplements provides instructors and students with innovative tools to support a variety of teaching and learning approaches. BiochemPortal

Molecular Evolution This icon signals the start of the many discussions that highlight protein commonalities or other molecular evolutionary insights. Only Lamino acids make up proteins(p.27) Increasing sophistication of glycogen phosphorylase Why this set of 20 amino acids?(p.33) regulation(p.628) Additional human globin genes(p.211) The a-amylase family (p.629) Fetal hemoglobin(p.213) A recurring motif in the activation of carboxyl groups(p.645) Catalytic triads in hydrolytic enzymes(p.260) Prokaryotic counterparts of the ubiquitin pathway Major classes of peptide-cleaving enzymes(p.263) and the proteasome(p.677) Zinc-based active sites in carbonic anhydrases(p.271) A family of pyridoxal-dependent enzymes(p.684) Common catalytic core in type II restriction Evolution of the urea cycle(p.688) enzymes (p.278) The P-loop NTPase domain in nitrogenase(p.708) P-loop NTPase domains(p.283) Similar transaminases determine amino acid chirality(p.713) Conserved catalytic core in protein kinases(p.302) Feedback inhibition(p.724) Why might human blood types differ?(p.335) Recurring steps in purine ring synthesis(p.741) Archaeal membranes(p.350) Ribonucleotide reductases(p.747) Ion pumps(p.374) Increase in urate levels during primate evolution(p.754) P-type ATPases(p.378) The cytochrome P450 superfamily(p.783) ATP-binding cassettes(p.378) DNA polymerases(p.821) Sequence comparisons of Na and Ca*channels(p.386) Thymine and the fidelity of the genetic message(p.841) Small G proteins (p.410) Sigma factors in bacterial transcription(p.858) Metabolism in the RNA world (p.447) Similarities in transcription between archaea and Why is glucose a prominent fuel?(p.455) eukaryotes(p.869) NAD*binding sites in dehydrogenases(p.469) Evolution of spliceosome-catalyzed splicing(p.881) The major facilitator superfamily of transporters(p.477) Classes of aminoacyl-tRNA synthetases(p.897) Isozymic forms of lactate dehydrogenase(p.490) Composition of the primordial ribosome(p.900) Evolution of glycolysis and gluconeogenesis(p.491) Homologous G proteins(p.903) The a-ketoglutarate dehydrogenase complex(p.507) A family of proteins with common ligand-binding Domains of succinyl CoA synthase(p.509) domains(p.926) Evolution of the citric acid cycle(p.518) The independent evolution of DNA-binding sites of Mitochondria evolution(p.527) regulatory proteins(p.927) Conserved structure of cytochrome c(p.543) Regulation by attenuator sites(p.932) Common features of ATP synthase and G proteins(p.550) CpG islands (p.946) Related uncoupling proteins(p.557) Iron-response elements(p.952) Chloroplast evolution(p.568) miRNAs in gene evolution(p.954) Evolutionary origins of photosynthesis (p.584) The odorant-receptor family(p.959) Evolution of the C pathway(p.600) Photoreceptor evolution(p.969) The coordination of the Calvin cycle and the pentose The immunoglobulin fold (p.984) phosphate pathway(p.609) Relationship of actin to hexokinase and prokaryotic Evolution of glycogen phosphorylase(p.627) proteins(p.1019)

x Only L amino acids make up proteins (p. 27) Why this set of 20 amino acids? (p. 33) Additional human globin genes (p. 211) Fetal hemoglobin (p. 213) Catalytic triads in hydrolytic enzymes (p. 260) Major classes of peptide-cleaving enzymes (p. 263) Zinc-based active sites in carbonic anhydrases (p. 271) Common catalytic core in type II restriction enzymes (p. 278) P-loop NTPase domains (p. 283) Conserved catalytic core in protein kinases (p. 302) Why might human blood types differ? (p. 335) Archaeal membranes (p. 350) Ion pumps (p. 374) P-type ATPases (p. 378) ATP-binding cassettes (p. 378) Sequence comparisons of Na1 and Ca1 channels (p. 386) Small G proteins (p. 410) Metabolism in the RNA world (p. 447) Why is glucose a prominent fuel? (p. 455) NAD1 binding sites in dehydrogenases (p. 469) The major facilitator superfamily of transporters (p. 477) Isozymic forms of lactate dehydrogenase (p. 490) Evolution of glycolysis and gluconeogenesis (p. 491) The a-ketoglutarate dehydrogenase complex (p. 507) Domains of succinyl CoA synthase (p. 509) Evolution of the citric acid cycle (p. 518) Mitochondria evolution (p. 527) Conserved structure of cytochrome c (p. 543) Common features of ATP synthase and G proteins (p. 550) Related uncoupling proteins (p. 557) Chloroplast evolution (p. 568) Evolutionary origins of photosynthesis (p. 584) Evolution of the C4 pathway (p. 600) The coordination of the Calvin cycle and the pentose phosphate pathway (p. 609) Evolution of glycogen phosphorylase (p. 627) Increasing sophistication of glycogen phosphorylase regulation (p. 628) The a-amylase family (p. 629) A recurring motif in the activation of carboxyl groups (p. 645) Prokaryotic counterparts of the ubiquitin pathway and the proteasome (p. 677) A family of pyridoxal-dependent enzymes (p. 684) Evolution of the urea cycle (p. 688) The P-loop NTPase domain in nitrogenase (p. 708) Similar transaminases determine amino acid chirality (p. 713) Feedback inhibition (p. 724) Recurring steps in purine ring synthesis (p. 741) Ribonucleotide reductases (p. 747) Increase in urate levels during primate evolution (p. 754) The cytochrome P450 superfamily (p. 783) DNA polymerases (p. 821) Thymine and the fidelity of the genetic message (p. 841) Sigma factors in bacterial transcription (p. 858) Similarities in transcription between archaea and eukaryotes (p. 869) Evolution of spliceosome-catalyzed splicing (p. 881) Classes of aminoacyl-tRNA synthetases (p. 897) Composition of the primordial ribosome (p. 900) Homologous G proteins (p. 903) A family of proteins with common ligand-binding domains (p. 926) The independent evolution of DNA-binding sites of regulatory proteins (p. 927) Regulation by attenuator sites (p. 932) CpG islands (p. 946) Iron-response elements (p. 952) miRNAs in gene evolution (p. 954) The odorant-receptor family (p. 959) Photoreceptor evolution (p. 969) The immunoglobulin fold (p. 984) Relationship of actin to hexokinase and prokaryotic proteins (p. 1019) This icon signals the start of the many discussions that highlight protein commonalities or other molecular evolutionary insights. Molecular Evolution

Clinical Applications This icon signals the start of a clinical application in the text.Additional,briefer clinical correlations appear in the text as appropriate. Osteogenesis imperfecta(p.45) Diseases resulting from defects in E3 proteins(p.676) Protein-misfolding diseases(p.55) Diseases of altered ubiquitination(p.678) Protein modification and scurvy(p.55) Using proteasome inhibitors to treat tuberculosis(p.679) Antigen detection with ELISA(p.88) Inherited defects of the urea cycle(hyperammonemia)(p.688) Synthetic peptides as drugs(p.96) Alcaptonuria,maple syrup urine disease,and Gene therapy(p.167) phenylketonuria(p.697) Functional magnetic resonance imaging(p.197) High homocysteine levels and vascular disease(p.719) Carbon monoxide poisoning(p.213) Inherited disorders of porphyrin metabolism(p.730) Sickle-cell anemia(p.209) Anticancer drugs that block the synthesis of thymidylate(p.749) Thalessemia(p.210) Adenosine deaminase and severe combined Aldehyde dehydrogenase deficiency(p.232) immunodeficiency(p.752) Action of penicillin (p.244) Gout(p.753) Protease inhibitors(p.264) Lesch-Nyhan syndrome(p.754) Carbonic anhydrase and osteoporosis(p.266) Folic acid and spina bifida(p.755) Isozymes as a sign of tissue damage(p.297) Second messengers derived from sphingolipids and Emphysema(p.306) diabetes(p.765) Vitamin K(p.310) Respiratory distress syndrome and Tay-Sachs Hemophilia(p.311) disease(p.765) Tissue-type plasminogen activator(p.312) Diagnostic use of blood-cholesterol levels(p.774) Monitoring changes in glycosylated hemoglobin(p.325) Hypercholesterolemia and atherosclerosis(p.776) Erythropoietin(p.330) Mutations in the LDL receptor(p.777) Hurler disease(p.331) The role of HDL in protecting against Blood groups(p.335) arteriosclerosis(p.778) I-cell disease(p.336) Clinical management of cholesterol levels(p.779) Influenza virus binding(p.339) Aromatase inhibitors in the treatment of breast Clinical applications of liposomes(p.354) and ovarian cancer(p.785) Aspirin and ibuprofen(p.358) Rickets and vitamin D(p.786) Digitalis and congenital heart failure(p.377) Antibiotics that target DNA gyrase(p.831) Multidrug resistance(p.378) Blocking telomerase to treat cancer(p.837) Long QT syndrome(p.392) Huntington disease(p.842) Signal-transduction pathways and cancer(p.420) Defective repair of DNA and cancer(p.842) Monoclonal antibodies as anticancer drugs(p.421) Detection of carcinogens(Ames test)(p.843) Protein kinase inhibitors as anticancer drugs(p.421) Antibiotic inhibitors of transcription(p.861) Vitamins(p.441) Burkitt lymphoma and B-cell leukemia(p.869) Lactose intolerance(p.471) Diseases of defective RNA splicing(p.877) Galactosemia(p.472) Vanishing white matter disease(p.908) Exercise and cancer(p.478) Antibiotics that inhibit protein synthesis(p.909) Phosphatase deficiency (p.514) Diphtheria(p.910) Defects in the citric acid cycle and the development Ricin,a lethal protein-synthesis inhibitor(p.911) of cancer(p.515) Induced pluripotent stem cells(p.944) Beriberi and mercury poisoning(p.517) Anabolic steroids (p.948) Mitochondrial diseases(p.558) Color blindness(p.970) Hemolytic anemia(p.609) The use of capsaicin in pain management(p.974) Glucose 6-phosphate deficiency(p.611) Immune-system suppressants(p.990) Glycogen-storage diseases(p.634) MHC and transplantation rejection(p.998) Carnitine deficiency(p.646) AIDS vaccine(p.999) Zellweger syndrome(p.652) Autoimmune diseases(p.1001) Diabetic ketosis(p.655) Immune system and cancer(p.1001) The use of fatty acid synthase inhibitors as Vaccines(p.1002) drugs(p.663) Charcot-Marie-Tooth disease(p.1016) Effects of aspirin on signaling pathways(p.665) Taxol (p.1019) xi

x i Osteogenesis imperfecta (p. 45) Protein-misfolding diseases (p. 55) Protein modification and scurvy (p. 55) Antigen detection with ELISA (p. 88) Synthetic peptides as drugs (p. 96) Gene therapy (p. 167) Functional magnetic resonance imaging (p. 197) Carbon monoxide poisoning (p. 213) Sickle-cell anemia (p. 209) Thalessemia (p. 210) Aldehyde dehydrogenase deficiency (p. 232) Action of penicillin (p. 244) Protease inhibitors (p. 264) Carbonic anhydrase and osteoporosis (p. 266) Isozymes as a sign of tissue damage (p. 297) Emphysema (p. 306) Vitamin K (p. 310) Hemophilia (p. 311) Tissue-type plasminogen activator (p. 312) Monitoring changes in glycosylated hemoglobin (p. 325) Erythropoietin (p. 330) Hurler disease (p. 331) Blood groups (p. 335) I-cell disease (p. 336) Influenza virus binding (p. 339) Clinical applications of liposomes (p. 354) Aspirin and ibuprofen (p. 358) Digitalis and congenital heart failure (p. 377) Multidrug resistance (p. 378) Long QT syndrome (p. 392) Signal-transduction pathways and cancer (p. 420) Monoclonal antibodies as anticancer drugs (p. 421) Protein kinase inhibitors as anticancer drugs (p. 421) Vitamins (p. 441) Lactose intolerance (p. 471) Galactosemia (p. 472) Exercise and cancer (p. 478) Phosphatase deficiency (p. 514) Defects in the citric acid cycle and the development of cancer (p. 515) Beriberi and mercury poisoning (p. 517) Mitochondrial diseases (p. 558) Hemolytic anemia (p. 609) Glucose 6-phosphate deficiency (p. 611) Glycogen-storage diseases (p. 634) Carnitine deficiency (p. 646) Zellweger syndrome (p. 652) Diabetic ketosis (p. 655) The use of fatty acid synthase inhibitors as drugs (p. 663) Effects of aspirin on signaling pathways (p. 665) Diseases resulting from defects in E3 proteins (p. 676) Diseases of altered ubiquitination (p. 678) Using proteasome inhibitors to treat tuberculosis (p. 679) Inherited defects of the urea cycle (hyperammonemia) (p. 688) Alcaptonuria, maple syrup urine disease, and phenylketonuria (p. 697) High homocysteine levels and vascular disease (p. 719) Inherited disorders of porphyrin metabolism (p. 730) Anticancer drugs that block the synthesis of thymidylate (p. 749) Adenosine deaminase and severe combined immunodeficiency (p. 752) Gout (p. 753) Lesch–Nyhan syndrome (p. 754) Folic acid and spina bifida (p. 755) Second messengers derived from sphingolipids and diabetes (p. 765) Respiratory distress syndrome and Tay–Sachs disease (p. 765) Diagnostic use of blood-cholesterol levels (p. 774) Hypercholesterolemia and atherosclerosis (p. 776) Mutations in the LDL receptor (p. 777) The role of HDL in protecting against arteriosclerosis (p. 778) Clinical management of cholesterol levels (p. 779) Aromatase inhibitors in the treatment of breast and ovarian cancer (p. 785) Rickets and vitamin D (p. 786) Antibiotics that target DNA gyrase (p. 831) Blocking telomerase to treat cancer (p. 837) Huntington disease (p. 842) Defective repair of DNA and cancer (p. 842) Detection of carcinogens (Ames test) (p. 843) Antibiotic inhibitors of transcription (p. 861) Burkitt lymphoma and B-cell leukemia (p. 869) Diseases of defective RNA splicing (p. 877) Vanishing white matter disease (p. 908) Antibiotics that inhibit protein synthesis (p. 909) Diphtheria (p. 910) Ricin, a lethal protein-synthesis inhibitor (p. 911) Induced pluripotent stem cells (p. 944) Anabolic steroids (p. 948) Color blindness (p. 970) The use of capsaicin in pain management (p. 974) Immune-system suppressants (p. 990) MHC and transplantation rejection (p. 998) AIDS vaccine (p. 999) Autoimmune diseases (p. 1001) Immune system and cancer (p. 1001) Vaccines (p. 1002) Charcot-Marie-Tooth disease (p. 1016) Taxol (p. 1019) This icon signals the start of a clinical application in the text. Additional, briefer clinical correlations appear in the text as appropriate. Clinical Applications