《生物化学》课程教学资源（文献资料）Lehninger Principles of Biochemistry，5th EDITION，David L. Nelson、Michael M. Cox

LEHNINGERPRINCIPLESOFBIOCHEMISTRYFIFTHEDITIONDavid L.NelsonProfessorof BiochemistryUniversity of Wisconsin-MadisonMichael M.CoxProfessor of BiochemistryUniversity of Wisconsin-MadisonW.H.FREEMANAND COMPANYNewYork

HNI PRINCIPLES OF BIOCHEMISTRY FIFTH EDITION David L. N e lso n Professor of Bio chemistry Uniu er sity of Wi s c onsin-M adi s on Michael M. Cox Profes sor of Bi,o chemistry Uni,uersity of Wi,sconsin-Madi,son l= W.H. FREEMAN AND COMPANY New York

About theAuthorsDavid L.Nelson,born in Fairmont,Minnesota, received hisBSinChemistry andBiology fron St.OlafCollege in1964 and earned hisPhD in Biochemistry atStanford Medical School under Arthur Kornberg.HewasapostdoctoralfellowattheHarvardMedicalSchoolwith Eugene P. Kennedy, who was one of AlbertLehninger's first graduate students.Nelson joined thefaculty of the University of Wisconsin-Madison in 1971and becameafull professor ofbiochemistryin1982.Heis the Director of the Center for Biology Education atthe Universityof Wisconsin-MadisonNelson's research has focused on the signal trans-ductions that regulate ciliary motion and exocytosis inthe protozoan Paramecium.The enzymes of signaltransductions,including avarietyofproteinkinases,areprimary targets of study.His researchgroup has usedenzyme purification,immunological techniques,elec-tron microscopy, genetics, molecular biology,and elec-David L.Nelson and Michael M.Coxtrophysiology to study these processes.Dave Nelson has a distinguished record as a lecturerand research supervisor.For 36 years he has taught anintensive surveyof biochemistryfor advancedbiochem-tions.At Stanford, hebegan work on theenzymes in-istry undergraduates in the life sciences. He has alsovolved in genetic recombination.The work focused par-taught a survey of biochemistry for nursing studentsticularly ontheRecA protein,designingpurification andand graduate courses on membrane structure and func-assay methods that are still in use, and lluminating thetion and on molecular neurobiology.Hehas sponsoredprocess of DNAbranchmigration.Exploration of the en-numerous PhD, MS, and undergraduate honors theses,zymes of genetic recombination has remained the cen-and has received awards for his outstanding teaching,tral theme of his research.including the Dreyfus Teacher-Scholar Award, theMike Cox has coordinated a large and active re-AtwoodDistinguishedProfessorship,and theUnterkoflersearch team at Wisconsin,investigating the enzymologyExcellence in Teaching Award from the University oftopology, and energetics of genetic recombination. AWisconsin System.In1991-1992hewasavisitingprofes-primary focus has been the mechanism of RecAsor of chemistry and biology at Spelman College.Hisprotein-mediatedDNAstrand exchange,theroleof ATPsecond love is history,and in his dotage he has begun toin the RecA system, and the regulation of recombina-teach the history of biochemistry to undergraduates andtional DNA repair. Part of the research program nowto collectantiquescientific instruments.focuses on organisrns that exhibit an especially robustcapacity for DNA repair, such as Deinococcus radiodu-Michael M.Cox was born in Wilmington,Delawarerans,andtheapplicationsof thoserepairsvstemstoIn hisfirstbiochemistry course,Lehninger'sBiochembiotechnology.Forthepast24years hehastaught (withistry was amajor influenceinrefocusinghis fascinationDave Nelson)the survey of biochemistry to undergradu-withbiology and inspiringhim to pursue a career inbio-ates and has lectured ingraduate courses on DNA struc-chemistry. After graduating from the University ofture and topology,protein-DNA interactions, and theDelaware in1974,Cox went to Brandeis University to dobiochemistryofrecombination.Amorerecentprojecthis doctoral work with William P.Jencks, and then tohas been the organization of a new course on profes-Stanford in 1979 for postdoctoral studywith I.Robertsionalresponsibilityforfirst-veargraduatestudents.HeLehman. He moved to the University of Wisconsin-has received awards for both his teaching and hisMadison in1983,and becamea full professor ofresearch,including theDreyfusTeacher-ScholarAwardbiochemistry in 1992.and the1989 Eli Lilly Award inBiological Chemistry.HisCox's doctoral research was on general acid andhobbies includegardening,wine collecting,and assistingbase catalysis as a model for enzyme-catalyzed reac-in the design of laboratory buildings

DaVid L. NelSOn, born in Fairmont, Minnesora, re￾ceived his BS in Chemistry and Biology from St. Olaf College in 1964 and earned his PhD in Biochemistry at Stanford Medical School under Arthur Kornberg. He was a postdoctoral felLow at the Harvard Medical School with Eugene P. Kennedy, who was one of Albert Lehninger's first graduate students. Nelson joined the faculty of the University of Wisconsin-Madison h 1971 and became a full professor of blochemrstry in 1982. He is the Director of the Center for Biology Education at the University of Wisconsin-Madison. Nelson's research has focused on the signal trans￾ductions that regulate ciliary motion and exocytosis in the protozoan Parameci,um. The enzymes of signal transductions, including a variety ofprotein kinases, are primary targets of study. His research group has used enzyme purification, immunological techniques, elec￾tron microscopy, genetics, molecuiar biology, and elec￾trophysiology to study these processes Dave Nelson has a distinguished record as a lecturer and research superuisor. For 36 years he has taught an intensive survey of brochemistry for advanced biochem￾istry undergraduates in the life sciences. He has also taught a survey of biochemistry for nursing students, and graduate courses on membrane structure and func￾tion and on molecular neurobiology. He has sponsored numerous PhD, MS, and undergraduate honors theses, and has received awards for his outstanding teaching, including the Dreyfus Teacher-Scholar Award, the Atwood Distinguished Professorship, and the Unterkofler Excellence in Teaching Award from the University of Wisconsin System. In 1991-1992 he was a visiting profes￾sor of chemistry and biology at Spelman College. His second love is history and in his dotage he has begun to teach the history of biochemistry to r-mdergraduates and to collect antique scientific instruments. MiChagl M. COX was born in Wlmington, I)elaware. In his first biochemistry course, Lehninger's Biochem- 'istry was a major influence in refocusing his fascination with biology and inspiring him to pursue a career in bio￾chemistry. After graduating from the University of Delaware inl974, Cox went to Brandeis University to do his doctoral work with MIIiam P Jencks, and then to Stanford in 1979 for postdoctoral study with I. Robert Lehman. He moved to the University of Wisconsin￾Madison in 1983, and became a full professor of biochemistry in 1992. Cox's doctoral research was on general acid and base catalysis as a model for enz;,rne-catalyzed reac￾tions. At Stanford, he began work on the enzymes in￾volved in genetic recombination. The work focused par￾ticularly on the RecA protein, designing puriflcation and assay methods that are still in use, and illuminating the process of DNA branch migration. Exploration of the en- 4,.rnes of genetic recombination has remained the cen￾tral theme of his research. Mike Cox has coordinated a large and active re￾search team at Wisconsin, investigating the enzymology, topology, and energetics of genetic recombination. A primary focus has been the mechanism of RecA protein-mediated DNA strand exchange, the role of ATP in the RecA system, and the regulation of recombina￾tional DNA repair. Part of the research program now focuses on organisms that exhibit an especially robust capacity for DNA repair, such as Dei,nococcus rad'i,odu￾rans, and the applications of those repair systems to biotechnology. For the past 24 years he has taught (with Dave Nelson) the suwey of biochemistry to undergradu￾ates and has lectured in graduate courses on DNA struc￾ture and topology, protein-DNA interactions, and the biochemistry of recombination. A more recent project has been the organization of a new course on profes￾sional responsibility for fi.rst-year graduate students. He has received awards for both his teaching and his research, including the Dreyfus Teacher-Scholar Award and the 1989 EIi Lilly Award in Biological Chemistry His hobbies include gardening, wine collecting, and assisting in the design of laboratory buildings. v l David [.Nelson and Michael M. Cox

A NoteontheNatureof Sciencenthistwenty-firstcentury,atypical scienceeducationreproducible observations,and the scientistmust reportoften leaves the philosophical underpinnings of sci-these observations with completehonesty.ence unstated, or relies on oversimplified definitions.AsThe scientifie method is actually a collection ofyou contemplatea career in science,it maybe useful topaths,all ofwhich maylead to scientific discovery.In theconsider once again the terins science, scientist, andhypothesis and experiment path,a scientist poses a hy-scientific methodpothesis, then subjects it to experimental test. Many ofScience isboth a way of thinking about the naturaltheprocesses thatbiochemistswork with everydaywereworld and thesumof theinformation and theorythatre-discoveredinthismanner.TheDNAstructureelucidatedsult fron such thinking.The power and success of sci-byJamesWatsonandFrancis Crick ledto thehypothesisenceflowdirectlyfrom itsrelianceon ideas thatcanbethat base pairing is the basis for information transfer intested: information on natural phenomena that can bepolynucleotide synthesis.This hypothesis helped inspireobserved,measured, and reproduced and theories thatthediscovery of DNAand RNApolymerases.have predictive value.The progress of science rests on aWatson and Crick produced their DNA structurefoundational assumption that is often unstated but cru-through a process of model building and calcula-cial to the enterprise:that the laws governing forces andtion, No actual experiments were involved, althoughphenomena existing in the universe are not subject tothe model building and calculations used data colchange.The Nobel laureate Jacques Monod referred tolected by other scientists.Many adventurous scientiststhis underlying assumption as the“postulate of objectivhaveappliedtheprocess ofecplorationandobserva-ity."The natural world can therefore be understood bytion as a path to discovery. Historical voyages of dis-applying a process of inquiry-the scientific methodcovery (Charles Darwin's 1831 voyage on H.M.SScience could not succeed in a universe that playedBeagleamongthem)helped tomaptheplanet, catalogtricks onus.Other than thepostulateof objectivity,sciits living occupants, and change the way we view theence makes no inviolate assumptions about thenaturalworld.Modern scientists followa sirnilarpath whenworld.A useful scientific idea is one that (D) has been orthey explore the ocean depths or launch probes tocan be reproducibly substantiated and (2) can be usedotherplanets.Ananalog of hypothesis and experimenttoaccuratelypredictnewphenormena.is hypothesis and deduction. Crick reasoned thatScientific ideas take manyforms. The terms that sci-there must be an adaptor molecule that facilitatedentistsusetodescribetheseforms havemeanings quitetranslation oftheinformationin messenger RNAintodifferentfromthoseappliedbynonscientists.Ahypoth-protein.This adaptor hypothesis led to the discovery ofesis is an idea orassumption that providesareasonabletransferRNAbyMahlon Hoagland andPaul Zamecnikandtestableexplanationforoneormoreobservations,Notallpaths todiscovery involveplanning.Serendip-but itmaylackextensive experimental substantiation.Aity often plays a role.The discovery of penicillin byscientific theoryis much more than a hunch.Itis anAlexander Fleming in1928,and ofRNAcatalysts byidea that has been substantiated to some extent andThomasCechin theearly1980s,werebothchancediscov-providesan explanationforabodyof experimental oberies,albeitby scientistswell prepared toexploit them.servations. A theory can be tested and built upon and isInspirationcan alsolead to importantadvances.Thepoly-thus a basis for further advance and innovation. When amerasechainreaction(PCR),nowacentralpartofbiotech-scientific theory has been repeatedly tested and vali-nology, was developed by Kary Mullis after a flash ofdated on many fronts,it can be accepted as a fact.inspiration duringaroadtripin northernCalifornia in1983.In one important sense,what constitutes scienceorThese rnany paths to scientific discovery can seema scientific idea is defined by whether or not it is pub-quite different, but they have sone important thingslished in the scientific literature after peer review byin common.They are focused on the natural world.other working scientists.About 16,000 peer-reviewedThey rely on reproducibleobservationand/or experi-scientific journals worldwidepublish some 1.4millionment.All oftheideas,insights,andexperimentalfactsarticles each year,a continuing rich harvest of informa-that arise from these endeavors can be tested andtion that is the birthright of every human being.reproduced by scientists anywhere in the world. All canSeientists are individuals who rigorously apply thebeusedbyother scientists tobuild newhypotheses andscientific method to understand the natural worldmake new discoveries.All lead to information that isMerely having an advanced degree in a scientific disciproperly included in the realn of science.Understand-pline does not make one a scientist, nor does the lack ofing our universe requires hard work. At the same time,such a degree prevent one from making important sci-no hunan endeavoris more exciting and potentially re-entific contributions.Ascientistmust be willing to chal-warding than trying,and occasionallysucceeding,tounlenge any idea when new findings demand it.The ideasderstand somepart of thenatural world.that a scientist accepts must be based on measurable,vii

I n this twenty-flrst century a typical science education I often leaves the philosophical underpinnings of sci￾ence unstated, or relies on oversimplified definitions. As you contemplate a career in science, it may be useful to consider once again the terms science, scientist, and scientifie method. Science is both a way of thinking about the natural world and the sum of the information and theory that re￾sult from such thinking. The power and success of sci￾ence flow directly from its reliance on ideas that can be tested: information on natural phenomena that can be observed, measured, and reproduced and theories that have predictive value. The progress of science rests on a foundational assumption that is often unstated but cru￾cial to the enterprise: that the laws governing forces and phenomena existing in the universe are not subject to change. The Nobel laureate Jacques Monod referred to this underlying assumption as the "postulate of objectiv￾ity." The natural world can therefore be understood by applying a process of inquiry-the scientific method. Science could not succeed in a universe that played tricks on us. Other than the postulate of objectivity, sci￾ence makes no inviolate assumptions about the natural world. A usefiil scientiflc idea is one that (1) has been or can be reproducibly substantiated and (2) can be used to accurately predict new phenomena. Scientrflc ideas take many forms. The terms that sci￾entists use to describe these forms have meanings quite different from those applied by nonscientists. Ahypoth￾eses is an idea or assumption that provides a reasonable and testable explanation for one or more observations, but it may lack extensive experimental substantiation. A sci,enti,fi,c theorA is much more than a hunch. It is an idea that has been substantiated to some extent and provides an explanation for a body of experimental ob￾servations. A theory can be tested and built upon and is thus a basis for further advance and innovation. When a scientiflc theory has been repeatedly tested and vali￾dated on many fronts, it can be accepted as a fact. In one important sense, what constitutes science or a scientiflc idea is defined by whether or not it is pub￾lished in the scientiflc literature after peer review by other working scientists. About 16,000 peer-reviewed scientific journals worldwide publish some 1.4 million articles each year, a continuing rich harvest of informa￾tion that is the birthright of every human being. Scientists are indireduals who rigorously apply the scientific method to understand the natural world. Merely having an advanced degree in a scientiflc disci￾pline does not make one a scientist, nor does the lack of such a degree prevent one from making important sci￾entific contributions. A scientist must be willing to chal￾lenge any idea when new findings demand it. The ideas that a scientist accepts must be based on measurable, reproducible observations, and the scientist must report these observations with complete honesty. The scientific method is actually a collection of paths, all of wtuch may lead to scientific discovery. In the hypothesi,s and erperiment path, a scientist poses a hy￾pothesis, then subjects it to experimental test. Many of the processes that biochemists work with every day were discovered in this manner. The DNA structure elucidated by James Watson and Francis Crick led to the hypothesis that base pairjrg is the basis for information transfer in po\mucleotide sS,nthesis. This hlpothesis helped inspire the discovery of DNA and RNA pol5.'rnerases. Watson and Crick produced their DNA structure through a process of model bui,ldi,ng and calcula￾t'ion. No actual experiments were involved, although the model building and calculations used data col￾lected by other scientists. Many adventurous scientists have applied the process oferp\oration and obserua￾t'ion as a path to discovery. Historical voyages of dis￾covery (Charles Darwin's 1831 voyage on H.M.S. Beagle among them) helped to map the planet, catalog its living occupants, and change the way we view the world. Modern scientists follow a similar path when they explore the ocean depths or launch probes to other planets. An analog of hypothesis and experiment is hypothesi,s and deduct'ion. Crick reasoned that there must be an adaptor molecule that facilitated translation of the information in messenger RNA into protein. This adaptor hypothesis led to the discovery of transfer RNA by Mahlon Hoagland and Paul Zamecnik. Not all paths to discovery involve planrung. Serendip￾i,tg often plays a role. The discovery of penicilJin by Alexander Fleming in 1928, and of RNA catalysts by Thomas Cech in the early 1980s, were both chance discov￾eries, albeit by scientists well prepared to exploit them. Irnpi,rati,on can also lead to important advances. The poly￾merase chain reaction (PCR), now a central part of biotech￾nology, was developed by Kary Mullis afler a flash of inspration dudng a road trip in northern Califomia in 1983. These many paths to scientiflc discovery can seem quite different, but they have some important things in common. They are focused on the natural world. They rely on reproducCble obseruat'ion anilor erperi￾ment. Nl of the ideas, insights, and experimental facts that arise from these endeavors can be tested and reproduced by scientists an5,where in the world. All can be used by other scientists to build new hypotheses and make new discoveries. All lead to information that is properly included in the realm of science. Understand￾ing our universe requires hard work. At the same time, no human endeavor is more exciting and potentially re￾warding than trying, and occasionally succeeding, to un￾derstand some part of the natural world. vtl

Prefacehefirstedition ofPrinciplesof Biochemistry,writtenWeareat the threshold of a newmolecular physiolIbyAlbert Lehningertwenty-fiveyears ago,has servedasogy in which processes such as membrane excitationthe starting point and the model for ourfour subsequentsecretion,hormone action,vision,gustation,olfaction,editions.Over that quarter-century, the world ofbiochem-respiration,muscle contraction.and cell movements willistryhas changedenormously.Twenty-fiveyears ago,notabe explicable in molecular terms and will become acces-single genome had been sequenced, not a single membranesibletogeneticdissectionandpharmacological manipu-proteinhadbeen solved by crystallography,andnotasin-lation.Knowledge of the molecular structures of thegleknockout mouse existed.Ribozymeshad justbeen dis-highly organized membrane complexes of oxidativecovered,PCR technology introduced,and archaeaphosphorylation and photophosphorylation,for exam-recognized asmembersofakingdomseparatefrombac-ple, will certainly bring deepened insight into thoseteria.Now, new genomic sequences are announced weekly,processes, so central to life. (These developments makenew protein structures even more frequently,and re-us wish we were young again, just beginning our careerssearchers have engineered thousands of differentknock-inbiochemical researchand teaching.Our book isnotout mice,with enormous promise for advancesin basicthe only thing that has acquired a touch of silver overbiochemistry, physiology, and medicine. This fifth editionthe years!)contains the photographs of 31 Nobel laureateswhohaveIn the past two decades, we havestrivenalways toreceivedtheirprizesforChemistryorforPhysiologyorMed-maintain the qualities that made the original Lehningericinesincethatfirstedition of Principlesof Biochemistry.texta classic-clearwriting,careful explanations of diffi-One major challenge of each edition has been to re-cult concepts,and communicating to studentsthewaysflect thetorrent ofnewinformationwithoutmakingthein which biochemistry is understood and practiced today.book overwhelming for students having theirfirst en-We have written together for twenty years and taught to-counter with biochemistry.This has required much care-gether for almost twenty-five.Our thousands of studentsful sifting aimed at emphasizing principles while stillat the University of Wisconsin-Madison over those yearsconveying the excitement of current research and itshavebeenan endless sourceofideas abouthowtoprespromisefor the future.The cover of this newedition ex-entbiochemistrymoreclearly:theyhaveenlightenedandemplifies this excitement and promise:in thex-ray struc-inspired us.We hope that this twenty-fifth anniversaryture of RNA polymerase, we see DNA, RNA, and proteinedition will enlighten and inspire current students of bio-in theirinformationalroles,inatomicdimensions,caughtchemistry everywhere,and perhapslead some ofthem toin the central act of information transfer.lovebiochemistryas wedo.Major Recent Advances in BiochemistryEvery chapter has been thoroughly revised and up-by plants,and ofbirdfeatherpigments deriveddated to include the most important advances in bio-fromcolored lipidsinplantfoods (Chapter10)chemistry including:Expanded andupdated section on lipidraftsandcaveolae to include newmaterial onmembraneConcepts of proteomes and proteomics,curvatureand theproteinsthatinfluenceit.andintroduced earlier in thebook (Chapter1)introducingamphitropicproteinsand annularNew discussion of amyloid diseases inthelipids (Chapter11)contextofproteinfolding (Chapter 4)Newsection on theemerging role of ribuloseNewsectiononpharmaceuticalsdevelopedfrom5-phosphate as a central regulator of glycolysisan understanding of enzymemechanism,usingandgluconeogenesis (Chapter15)penicillin and HIVprotease inhibitors as examplesNewBox16-1,MoonlightingEnzymes:Proteins(Chapter6)with More Than One Job New discussion of sugar analogs as drugs thatNew section on therole of transcription factorstarget viral neuraminidase (Chapter7)(PPARs)inregulationof lipidcatabolismNew material on green fluorescent protein(Chapter17)(Chapter9)Revised and updated section on fatty acidNew section on lipidomics (Chapter 10)synthase,including newstructural informationNewdescriptions of volatile lipids used as signalsonFASI(Chapter21)vili

first edition of Pnnctples oJ Bi,ochenuistry, v'ritten Albert Lehninger twenty-flve years ago, has served as the starting point and the model for our four subsequent editions. Over that quarter-century the world of biochem￾istry has changed enormously. TWenty-flve years ago, not a single genome had been sequenced, not a single membrane protern had been solved by crystallography, and not a sin- $e hnockout mouse existed. RibozJrmes had just been dis￾covered, PCR technology introduced, and archaea recognized as members of a kingdom separate from bac￾teria Now, new genomic sequences are announced weekly, new protern structures even more frequently, and re￾searchers have engineered thousands of djfferent lcrock￾out mice, with enormous promise for advances in basic biochemistry physiology, and medicine. This ffih edition contains the photographs of 31 Nobel laureates who have received theirprizes for Chemistry or for Physiologr or Med￾icine since that first edition of Prhrciples of Binchemistry. One major challenge of each edition has been to re￾flect the torrent of new information without making the book overwhelming for students having their first en￾counter with biochemistry. This has required much care￾ful sifting aimed at emphasizing principles while still conveying the excitement of current research and its promise for the future. The cover of this new edition ex￾empli-fles this excitement and promise: in the x-ray struc￾ture of RNA polymerase, we see DNA, RNA, and protein in their informational roles, in atomrc dimensions, caught in the central act of in-formation transfer. Major Recent Advances in Biochemistry Every chapter has been thoroughly revised and up￾dated to include the most important advances in bio￾chemistry including: r Concepts of proteomes and proteomics, introduced earlier in the book (Chapter 1) r New discussion of amyloid diseases in the context of protein folding (Chapter 4) r New section on pharmaceuticals developed from an understanding of enzyme mechanism, using penicillin and HIV protease inlLibitors as examples (Chapter 6) r New discussion of sugar analogs as drugs that target viral neuraminidase (Chapter 7) r New material on green fluorescent protein (Chapter 9) r New section on lipidomics (Chapter 10) r w descriptions of volatile lipids used as signals vi We are at the threshold of a new molecular physiol￾ogy in which processes such as membrane excitation, secretion, hormone action, vision, gustation, olfaction, respiration, muscle contraction, and cell movements will be explicable in molecular terms and will become acces￾sible to genetic dissection and pharmacological manipu￾lation. Knowledge of the molecular structures of the highly organized membrane complexes of oxidative phosphorylation and photophosphorylation, for exam￾ple, will certainly bring deepened insight into those processes, so central to life. (These developments make us wish we were young again, just beginning our careers in biochemical research and teaching. Our book is not the only thing that has acquired a touch of silver over the years!) In the past two decades, we have striven always to maintain the qualities that made the original Lehninger text a classic-clear wdting, careftrl explanations of diffl￾cult concepts, and communicating to students the ways in which biochemistry is understood and practiced today. We have written together for twenty years and taught to￾gether for almost twenty-flve. Our thousands of students at the University of Wisconsin-Madison over those years have been an endless source of ideas about how to pres￾ent biochemistry more clearly; they have enlightened and rnspired us. We hope that this twenty-flfth aruLiversary edition will erLlighten and inspire current students of bio￾chemistry everywhere, and perhaps lead some of them to Iove biochemistry as we do. by plants, and of bird feather pigments derived from colored lipids in plant foods (Chapter 10) Expanded and updated section on lipid rafrts and caveolae to rnclude new material on membrane curvature and the proteins that influence it, and introducng amphitropic proteins and anmrlar Iipids (Chapter 11) New section on the emerging role of ribulose 5-phosphate as a central regulator of $ycolysis and gluconeogenesis (Chapter 15) New Box 16-1, Moonlighting Erzymes: Proteins with More Than One Job New section on the role of transcription factors (PPARs) in regulation of lipid catabolism (Chapter 17) Revised and updated section on fatty acid synthase, including new structural information on FAS I (Chapter 21)

PrefaceUpdated coverage of(a)(b)the nitrogen cycle,KRincluding newBoxDH22-1, Unusual LifeMATStyles of the Obscurebut Abundant,discussing anammoxDHWheebacteria (Chapter 22)KR-New Box 24-2,Epigenetics,NucleosomeMATKSStructure,and HistoneVariants describing theKSMATDHERKRACPErole of histonemodification andFIGURE 21-3 The structure offatty acid synthase type Isystems.nucleosome depositioninthetransmissionofNew information on theroles of RNAepigeneticinformationin heredityin protein biosynthesisNewinformationontheinitiationof replication(Chapter 27)and thedynamicsat thereplicationfork,Newsectiononriboswitches-introducingAAA+ATPases and theirfunctions(Chapter 28)inreplicationand otheraspectsofDNAmetabolism (Chapter 25)New Box 28-1, Of Fins, Wings,Beaks,and ThingsNewsection ontheexpandedunderstandingofdescribingtheconnections betweenevolutionBtheroles of RNAin cells (Chapter 26)anddevelopmentBiochemical Methods(b)(a)Gene fortarget proteinGlutathioneGla-Op-G!An appreciation of biochemistry oftenGemefarCST(GSH)requires an understanding of how bio-chemical information is obtained. SomeGenefor fasion proteitGlutathioe-S-ranferase(GST)of the newmethods or updates describedFiGURE9-12 The use of tagged proteins in protein purifi-in this edition are:cation.Theuse ofa GST tag is ilustrated, (a) Glutathione-S-transferase (GST) is a small enzyme (depictedhere by the purple icon) that binds glutathione (a gluta-Circular dichroism (Chapter4)materesiduetowhichaCys-Glydipeptideisatached atProre codl extthe carboxyl carbon of the Clu side chain, hence the ab-MeasurementofglycatedatftheBretetemtbreviation GSH). (b)The GST tag is fused to thecar.hemoglobin as an indicatorofboxyl terminus of the target protein by geneticaveragebloodglucoseconcentration,engineering,The tagged protein is expressed in hostcells, and is present in the crude extract when the cellsover days,inpersons with diabetesare lysed.Theextract is subjected to chromatographyAdd proteinmediu(Chapter7)on a column containing a medium with immobilizedto columnGSTtglutathione.The GST-tagged protein binds to the gluUseof MALDI-MS in determination oftathione, retarding its migration through the columnoligosaccharidestructure(Chapter7)whie the other proteins wash through rapidly.Thetagged protein is subsequentiy eluted from the columnForensicDNA analysis,amajor updatewithasolutioncontainingelevated saltconcentrationofree glutathione.covering modern STR analysis (Chapter9)More onmicroarrays (Chapter9)Use of tags for protein analysis andpurification (Chapter9)Elute fusion proteinPETcombinedwith新FIGURE9-12CT scans to pinpoint cancer(Chapter 14)Development of bacterial strainswith alteredge图netic codes, for site-specific insertion of novelChromatin immunoprecipitation and ChiP-chipamino acids intoproteins (Chapter27)experiments (Chapter24)

Updated coverage of the nitrogen cycle, including new Box 22-1, Unusual Life Styles of the Obscure but Abundant, discussing anammox bacteria (Chapter22- New Box 24-2, Epigenetics, Nucleosome Structure, and Histone Variants describing the role of histone modification and nucleosome deposition in the transmission of epigenetic information in heredity New information on the initiation of replication and the dymamics at the replication fork, introducing AAA+ ATPases and their functions in replication and other aspects of DNA metabolism (Chapter 25) New section on the expanded understanding of the roles of RNA in cells (Chapter 26) Biochemical Methods An appreciation of biochemistry often requires an understanding of how bio￾chemical information is obtained. Some of the new methods or updates described in this edition are: r Circular dicluoism (Chapter 4) r Measurement of glycated hemoglobin as an indicator of average blood glucose concentration, over days, in persons with diabetes (Chapter 7) r Use of MALDI-MS in determination of oligosaccharide structure (Chapter 7) r Forensic DNA analysis, a major update covering modern STR analysis (Chap￾ter 9) r More on microarrays (Chapter 9) r Use of tags for protein analysis and purification (Chapter 9) r PET combined with CT scans to pinpoint cancer (Chapter 14) r Chromatin immunoprecipitation and ChlP-chip experiments (Chapter 24) Preface FIGURE 21-3 The structure offatty acid synthase type I systems. New information on the roles of RNA in protein biosynthesis (Chapter 27) New section on riboswitches (Chapter 28) New Box 28-1, Of Fins, Whgs, Beaks, and Things, describing the cormections between evolution and development tx r Development of bacterial strains with altered ge netic codes, for site-specific insertion of novel amino acids into proteins (Chapter 27) Glutathione (GSH) G€ne for tusion prctein I v Express tu8ion Foteh h a cell flcuflt 9-12 The use of tagged proteins in protein purifi￾cation. The use of a CST tag is illustrated (a) Clu￾tathione-s-transferase (CST) is a small enzyme (depicted here by the purple icon) that binds glutathione (a Sluta￾mate residue to which a Cys-Cly dipeptide is attached at the carboxyl carbon of the Clu side chain, hence the ab￾breviation CSH) (b) The CST tag is fused to the catr boxyl terminus of the target protein by Senetic engineering The tagged protein is expressed in host cells, and is present in the crude extract when the cells are lysed The extract is subjected to chromatography on a column containing a medium with immobilized Slutathione The CsT{agged protein binds to the 8lu￾tathione, retardinB its migration through the column, while the other proteins wash through rapidly The tagged protein is subsequently eluted from the column with a solution containing elevated salt concentration or free glutathione Add gotein EIub fusion plobin IIGURE 9-12

PrefaceMedicallyRelevantExamplesThis icon is used throughout the book to denoteBox15-3,GeneticMutationsThat Lead toRare平material of special medical interest. As teachers,Forms of Diabetesour goal is for students to learn biochemistry and toMutations in citric acid cycleenzymesthatlead tounderstand its relevance to a healthier life and acancer(Chapter16)healthierplanet.Wehaveincludedmanynewexam-Pernicious anemia and associated problems in strictples that relate biochemistry to medicine and to healthvegetarians (Chapter18)issues ingeneral.Someofthemedical applications newUpdated information on cyclooxygenase inhibitorsto this edition are:(pain relievers Vioxx, Celebrex, Bextra)The role of polyunsaturated fatty acids and trans(Chapter 21)fatty acids in cardiovasculardisease (Chapter 10)HMG-CoA reductase (Chapter 21) and Box 21-3,Gprotein-coupledreceptors(GCPRs)andtheTheLipidHypothesis and theDevelopmentofrange ofdiseases for which drugs targeted toStatinsGPCRs are being used ordeveloped (Chapter12)Box 24-1, Curing Disease by InhibitingG proteins, the regulation of GTPase activity,Topoisomerases, describing the use ofand themedical consequences of defectiveGproteintopoisomerase inhibitors in thetreatmentfunction(Chapter12),includingnewBox12-2,of bacterialinfectionsand cancer,includingGProteins:Binary Switches inHealth andDiseasematerialon ciprofloxacin (theantibioticeffectiveBox12-5,Developmentof ProteinKinaseInhibitorsforanthrax)for CancerTreatmentBox14-1,HighRateofGlycolysis inTumorsSuggestsTargetsfor Chernotherapy and Facilitates DiagnosisSpecial Theme:Understanding Metabolismthrough ObesityandDiabetesObesity and its medical consequences-cardiovascu-LiverAdiposetissuelar disease and diabetes-are fast becoming epidemicin the industrialized world,and we include newmate-rial onthebiochemical connections between obesityand health throughout this edition. Our focus on dia-Fat aynthesisFatevnthbetesprovides an integrating theme throughout theFattyacidoxidationand storageFatty acid oxidndstoranStarvationrespotAdipokine prochapters on metabolism and its control, and this will,Thermogenwe hope,inspire some students tofind solutions forthis disease. Some of the sections and boxes thatPPARPPARYPPAROhighlight the interplay of metabolism, obesity, anddiabetes are:InsulinFattvanidosidationFatty acid oxidsensitivityUntreated Diabetes Produces Life-Threatening Acinermogenesis+dosis (Chapter 2)Box7-1,BloodGlucoseMeasurements intheMuscleDiagnosis and TreatmentofDiabetes,introducinghemoglobinglycationandAGEsandFIGURE23-42theirrole in thepathology of advanced diabetesBox11-2,Defective Glucoseand WaterTransportAdiposeTissue Generates Glycerol 3-phosphateinTwoFormsof Diabetesby Glyceroneogenesis (Chapter 21)Glucose Uptake Is Deficient in Type 1Diabetes MelDiabetes Mellitus Arises from Defects in Insulinlitus (Chapter14)Production.orAction(Chapter23)Ketone Bodies Are Overproduced in Diabetes andSection23.4,Obesityand theRegulation of Bodyduring Starvation(Chapter17)Mass,discusses therole ofadiponectin and insulinSomeMutationsinMitochondrial Genomes Causesensitivity andtype2diabetesDisease (Chapter19)Section23.5,Obesity,theMetabolicSyndrome,andDiabetes Can ResultfromDefects in theMitochonType2Diabetes,includes adiscussion ofmanagingdriaofPancreaticβCells(Chapter19)type 2 diabetes with exercise, diet, and medication

x - Preface Medically Relevant Examples This icon is used throughout the book to denote material of special medical interest. As teachers, our goal is for students to learn biochemistry and to understand its relevance to a healthier life and a healthier planet. We have included many new exam￾ples that relate biochemistry to medicine and to health issues in general. Some of the medical applications new to this edition are: r The role of polyunsaturated fatty acids and trans fatty acids in cardiovascular disease (Chapter 10) r G protein-coupled receptors (GCPRs) and the range of diseases for which drugs targeted to GPCRs are being used or developed (Chapter 12) r G proterns, the regulation of GTPase activity, and the medical consequences of defective G protein function (Chapter 12), including new Box 12-2, G Proteins: Binary Switches in Health and Disease r Box 12-5, Development of Protein Kinase Inhibitors for Cancer Tleatment r Box 14-1, Htgh Rate of Glycolysis in Tlmors Suggests Targets for Chemotherapy and Facrlitates Diagnosis Special Theme: Understanding Metabolism Obesity and its medical consequences-cardiovascu￾lar disease and diabetes-are fast becoming epidemic in the industrialized world, and we include new mate￾rial on the biochemical connections between obesity and health throughout this edition. Our focus on dia￾betes provides an integrating theme throughout the chapters on metabolism and its control, and this will, we hope, inspire some students to find solutions for this disease. Some of the sections and boxes that highlight the interplay of metabolism, obesity, and diabetes are: r Untreated Diabetes Produces Life-Threatenine Aci dosis (Chapter 2) r Box 7-1 , Blood Glucose Measurements in the Diagnosis and T?eatment of Diabetes, introducing hemoglobin glycation and AGEs and their role in the pathology of advanced diabetes r Box 11-2, Defective Glucose and Water T?ansport in TWo Forms of Diabetes r Glucose Uptake Is Deficient in T}pe 1 Diabetes Mel Iitus (Chapter 14) r Ketone Bodies Are Overproduced in Diabetes and during Starvation (Chapter 17) r Some Mutations in Mitochondrial Genomes Cause Disease (Chapter 19) r Diabetes Can Result from Defects in the Mitochon dria ofPancreatic B Cells (Chapter 19) r Box 15-3, Genetic Mutations That Lead to Rare Forms of Diabetes r Mutations in citric acid cycle enzyrnes that lead to cancer (Chapter 16) r Pernicious anemia and associated problems in strict vegetarians (Chapter 18) r Updated information on cyclooxygenase hhibitors (pain relievers Vioxx, Celebrex, Bextra) (Chapter 21) r HMG-CoA reductase (Chapter 21) and Box 21-3, The Lipid Hypothesis and the Development of Statins r Box 24-1, Curing Disease by Inhibiting Topoisomerases, describing the use of topoisomerase inhibitors in the treatment of bacterial rnfections and cancer, including material on ciprofloxacin (the antibiotic effective for anthrax) through 0besity and Diabetes r Adipose Tissue Generates Glycerol 3-phosphate by Glyceroneogenesis (Chapter 21) r Diabetes Mellitus Arises from Defects in Insulin Production or Action (Chapter 23) r Section 23.4, Obesity and the Regulation of Body Mass, discusses the role of adiponectin and insulin sensitivity and tlpe 2 diabetes r Section 23.5, Obesity, the Metabolic S;'ndrome, and T\pe 2 Diabetes, includes a discussion of managing type 2 diabetes with exercise, diet, and medication @ Fat synthesie Fatty acid oxidatioD and storage Stawation response and storage Fatty acid oxidati Adipokineproduction Themogenesis FIGURE 23-42

PrefaceAdvances in Teaching BiochemistryWORKEDEXAMPLE11-3Energetics of Pumpingby SymportRevising this textbook is never just an updating exercise. At least as much timeglucosel;Calculate the maximumratio that can beIglucoselounis spent reexamining how the core topics of biochemistry are presented. Weachieved by the plasma membrane Nat-glucose syrt-haverevised each chapterwith an eyetohelping studentslearn andmastertheporter of an epithelial cell, when [Na*lr, is 12 m[Nalo is 145 mM, the mebrane potential is-50 mVfundamentalsofbiochemistry.Studentsencounteringbiochemistryforthefirst(inside negative), and the temperature is 37°C.time oftenhavedifficultywithtwokeyaspectsof the course:approachingquan-Solution: Using Equation 11-4 (p 396), we can calculate the energy inherent in an electrochemical Natitativeproblens and drawing on what theylearned inorganicchemistrytohelpgradient-that is, the cost of moving one Nat ion upthis gradientthem understand biochemistry.Those same students must also learn a com-INalat+2320plexlanguage,with conventions thatareoftenunstated.WehavemadesomeAG,-RTInNalmajor changes in the book to help students cope with all these challenges:We then substitute stadard values for R, T, and 3, andnew problem-solving tools, a focus on organic chemistry foundations, andthe given values for [Na'] (expressed as molar concen-trations),+1 for Z (because Nahas a positivehighlightedkey conventions.charge), and 0.050 Vfor .Note that themembranepotential is-50 mV (inside negative),so the change inpotential when an lon moves from inside to outside is50mVNewProblem-SolvingToolsG(8315 /mol-K)(310Kn45×101.2×10-2+ 1(96,500 J/V-mol)(0.050 V)Newin-text Worked Examples help students improvetheir 11.2kJ/molquantitativeproblem-solving skills,taking them through some of theThis G, Is the potential energy permole of Na in themostdifficultequations.Nagradient that is availabie to pump ghucose.Giventhat two Na+ ions pass down their electrochemical gra-Morethan100 newend-of-chapterproblemsgive studentsdient and into the cellfor each glucose carried in bysymport, theenergy available to pump 1mol ofglucosefurtheropportunitytopracticewhattheyhavelearnedis 2×112kJ/mol =22.4kJ/mol.Wecan now calculatethe concentration ratio of glucose that can be achievedNewDataAnalysisProblems(oneattheendofeachchapter),conby this pump (trotn Equation 11-3,p.396):tributed byBrian White of the University of Massachusetts-Boston,en[glucosel.,.AG, =RTInIglucosel....courage students to synthesize what theyhavelearned and applytheirRearranging, then substituting the vaues of G,R, andknowledge to the interpretation of datafrom the literature7,gives22.4 kJ/molIglucoseln408.69(8.315J/mol-KX310K)gluconeltR7Focus on OrganicChemistryFoundations 5.94× 10NewSection13.2,Chemical logicand commonbiochemicalWORKEDEXAMPLE11-3reactions, discusses the common biochemical reaction types thatunderlie all metabolicreactions.Chemical logic is reinforced in the discussions ofCH,OPOScentral metabolicpathways.NADNADHOOHuhu3-phosphateMechanism figures feature step-by-step?descriptionstohelpstudentsunderstandtheorsldehydsphaCysreaction process.dehydrogennsCysalenttiobsmiaInthepresentation ofreaction mechanisms,ioaban tho3ahot.2peftheCya reaidwe consistentlyuse a set of conventionsCH,OPONADintroducedand explained in detail with theHCOHCB,OPOfirstenzyme mechanism encounteredHOOM(chymotrypsin,pp.208-209).SomeofoCrthe new problems focus on chemicalThe ensyerbstretemechanismsand reinforcemechanisticthemes?heNAD-beisd to thcCH,OPOHCOH/o.CHOPOSNADNADHKey Conventions专NAIDHCOH0-0NADRIn this edition, many of the conventions that are soTae NADH ptotuct leaves theCyaCynecessaryforunderstandingeachbiochemicaltopicoNATand the biochemical literature are broken out of theFIGURE14-7text and highlighted. These Key Conventionsinclude clear statements of many assumptions andconventions that students are often expected to assirnilate withoutKEY CONVENTION:When an aminoacid sequence ofapeptide,polypeptide, or protein is displayed, the amino-being told (for example, peptide sequences arewritten from amino-terminal end is placed on the left, the carboxyl-terminalto carboxyi-terminal end, left to right; nucleotide sequences areend on the right. The sequence is read left to right, be-writtenfrom 5'to3'end,lefttoright).ginning with the amino-terminal end

Advances in Teaching Biochemistry Revising tlus textbook is never just an updating exercise. At Ieast as much time is spent reexamining how the core topics of biochemrstry are presented. We have revised each chapter with an eye to helping students learn and master the fundamentals of biochemistry. Students encountering biochemistry for the first trme often have difflculty with two key aspects of the course: approaching quan￾titative problems and drawing on what they learned in orgaruc chemistry to help them understand biochemistry. Those same students must also learn a com￾plex language, with conventions that are often unstated. We have made some major changes in the book to help students cope with all these challenges: new problem-solving tools, a focus on organic chemistry foundations, and highlighted key conventions. New Problem-5olving Tools r New in-text Worked Examples help students improve their quantitative problem-solving skills, taking them through some of the most difficult equations. r More than 100 new end-of-chapter problems give students further opportunity to practice what they have learned. r New Data Analysis Problems (one at the end of each chapter), con tributed by Brian White of the University of Massachusetts-Boston, en courage students to slmthesize what they have learned and apply their knowledge to the interpretation of data from the literature. Focus on 0rganic (hemistry Foundations r New Section 13.2, Chemical logic and common biochemical reactions, discusses the common biochemical reaction types that underlie all metabolic reactions. r Chemical logic is reinforced in the discussions of central metabolic pathways. r Mechanism figures feature step-by-step descriptions to help students understand the reaction process. r In the presentation of reaction mechanisms, we consistently use a set of conventions introduced and explained in detail with the first enzyme mechanism encountered (chymotrypsin, pp. 208-209). Some of the new problems focus on chemical mechanisms and reinforce mechanistic themes. Key (onventions In this edition, many of the conventions that are so necessary for understanding each biochemical topic and the biochemical literature are broken out of the text and highlighted. These Key Conventions FIGURE 14-7 include clear statements of many assumptions and conventions that students are often expected to assimilate without being told (for example, peptide sequences are uritten from amino￾to carboxyl-terminal end, Ieft to right; nucleotide sequences are written from 5' to 3' end left 1n rioht) KtY (0NVENTI0N: When an amino acid sequence of a peptide, polypeptide, or protern is displayed, the amino￾terminal end is placed on the left, the caxboxyl-terminal end on the right The sequence is read left to dght, be￾giming with the amino-terminal end I f WORKED EXAMPII 1l-3 EnergeticsofPumping bY SYnPort lglumseli, Cahulal,e lhe maimm .': -= mtio that can be lglucosejour achieved by the plasma membrme Na*-glucose sym￾porter of an epithelial cell, when [Na-]6 is 12 mM, [Nat]."1 is 145 ro, the membrme potential is -50 mV (inside negative), and the temperature is 37 'C Soltrtion: Using Equation 11-4 (p 396), we can calcu￾late the energy inherent in an electrochemical Na+ gradient-that is, the cost of moving one Na- ion up this gradientl AG. _ R?lnry+ + zr a,r, ' tNal," We then substitute standard values for-&, ?, and J, and the given values for [Na-] (expressed as molar concen￾trations), +l for Z (because Na+ has a positive charge), md 0 050 V for a,y' Note that the membrane potential is -50 mV (inside negative), so the chmge in potential when m ion moves from inside to outside is 50 mV. AGt : (8 315 J/mol K)(3to rcm 1 45 x 10-' 1.2xto 2 + 1(96,500 JV.mol)(0 050 V) = 11 2 kJ/mol This AGr is the potential energy per mole of Na- in the Na* $adient that is available to pmp glucose Given that two Na- ions pass dom their electrochemical gra￾dient md into the cell for each glucose canied in by slmport, the energy available to pmp 1 mol of Llucose is2 x II2 kJ/mol = 22 4 kJ/mol We can now calculate the concentration ratio of Elucose that cm be achieved by this pmp (from Equation l1-3, p 396): _ _. [glucose]r lG, = ft?ln:i￾Lgrucoselour Remnuing, then substituting the values of AGt,&, and ?, gives . [g]ucosel* AG, 22.4kJ/mol 'n lir"o""l., n,r = E:rs .llorot ' t< u slo{(, - o ot lglucosel,. lglucose]""t - WORKED EXAMPLE 11-3 cHooPoi t - NS* HCOH n,t"b cvs I a ovalmt thioheninetal 6l lbkry. foms bHeen ih€ v subshate md the -S￾L PUP of he cys residu€ NAnl cu"OPO? "-\ t- - Y9OH u!c4 I S I cv" CF Gtyceraldehyde 3-phosphaE \e , Fodatim of etrzFe. subFate @nplex fre dive.sik C)€ ha! e duced pf, (5 5 in€bad of 8) when NAD+ iE bu4 ed is in the Eore readive, ffiolab fom fre @alent thiqbr thkago betuem the suhEaE sd €nzFe udese ph6phdobEis (sthck by 4) releasiry fre se@nd pdud, l,g-bbphdphqly@me o 'P O H \ - P.ND+ fr€ N0H prcduct leaves fte active sik ud is replaced by another nolecule of NS+. I The €nzr€aubst ah ^L intemediatetuoddiledby \tl tuNs*boudbse NsH CH,OPO: HCOH C:O S cvg NS' Glycerddehyd€ 3-phosphah cH"oPo"'- 1-_' Ns, Hcor/'o. ./ c:o CF

xIPreface1-4292-1911-4), fully optimized for maximum visibil-Media and Supplementsity in the lecture hall.Afull packageofmediaresourcesandsupplementspro-Animated Enzyme Mechanisms and Animatedvides instructors and students with innovative tools toBiochemical Techniques are available in Flashsupport a variety of teaching and learning approaches.filesandpreloadedintoPowerPoint,inbothPCandAll these resources are fully integrated with the styleMacintoshformats,forlecturepresentation.(Seeand goals ofthefifth edition textbook.listofanimationtopicsontheinsidefrontcover.)Alist of ProteinDataBank IDsfor the structureseBookin thetextisprovided, arrangedbyfigurenumber.Anew feature in this edition is an index to all struc-This online version of the textbooktures in the Jmol interactive Web browser applet.combinesthecontents of theprintedLivingGraphs illustratekey equations fromn thebook, electronic study tools, and atextbook,showing thegraphicresults of changingfull complement of student mediaparameters.specifically created to support thetext.TheeBook alsoprovidesusefulAcomprehensiveTestBank inPDFand editablematerial for instructors.Word formats includes150multiple-choiceandeBookstudytoolsincludeinstantnavigation toanyshort-answerproblemsperchapter,rated bylevelsection orpage of thebook, bookmarks,highlighting,ofdifficulty.note-taking,instantsearchforanyterm,pop-upkeyterm definitions,and a spoken glossary.The text-specific student media,fully integratedthroughouttheeBook,includeanimatedenzymeAdditional Student Mediamechanisms,animatedbiochemicaltechriques,problem-solvingvideos,molecularstructureStudents areprovided with media designedto enhancetutorials in Jmol, Protein Data BankIDs in Jmol, livtheir understanding of biochemical principles and im-inggraphs,and onlinequizzes (eachdescribedunprovetheir problem-solving ability.All student media,der"Additional Student Media"below).along with the PDB Structures and Living Graphs, arealso in the eBook, and many are available on the bookInstructorfeatures include the ability to addWebsite(www.whfreeman.com/lehninger5e).Thenotes orfiles to any pageand to share thesestudent media include:notes with students. Notes may include text, Weblinks,animations,orphotos.InstructorscanalsoNewProblem-Solvingassign the entire text or a custom version of theVideos,created byeBook.ScottEnsignofUtahStateUniversityprovide24/7onlineproblem-solvinghelpto students. Through aAdditional InstructorMediatwo-partapproach,each10-minute video coversaInstructors are provided with a comprehensive setkeytextbookproblemrepre-of teaching tools,each developed to support the text,senting atopicthatstudents traditionallystruggletolecturepresentations,andindividualteachingstyles.Allmaster.Dr.Ensignfirstdescribes aprovenproblem-instructor media areavailable for download on thesolving strategy and then appliesthestrategytothebookWebsite(www.whfreeman.com/lehninger5e)problem at hand in clear,concise steps.Students canand on the Instructor Resource CD/DVD (ISBNeasilypause,rewind,and reviewany stepsasthey1-4292-1912-2).Thesemedia tools include:wish until they firmly grasp not just the solution butFully optimized JPEGfiles of everyfigure, photo,also thereasoning behind it.Working throughtheand table in the text, with enhanced color, higherproblems inthis way is designed to makestudentsresolution,and enlarged fonts.Thefileshavebeenbetterand more confident at applyingkeystrategiesreviewed by course instructors and tested inaastheysolveothertextbookandexamproblems.largelecturehall toensuremaximum clarityStudent versions of the Animated Enzymeand visibility.The JPEGs are also offered inMechanisms and Animated Biochemicalseparate files and in PowerPoint format for eachTechniques help students understand keychapter.mechanisms and techniques at their own pace.The150mostpopular images in the textbook areFor acomplete list ofanimation topics, seetheavailable in an Overhead Transparency Set (ISBNinsidefront cover

Mediand 5upplements A fulI package of media resources and supplements pro￾vides instructors and students with innovative tools to support a variety of teaching and learning approaches. All these resources are fully integrated with the style and goals of the fifth edition textbook. eBook 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. The eBook also provides usefirl material for instructors. r eBook study tools include instant navigation to arry section or page of the book, boolanarks, higlrlightirg, note-taking, instant search for any term, pop-up key￾term definitions, and a spoken glossary. r The text-speci-flc student media, fully integrated throughout the eBook, include animated enzyme mechanisms, animated biochemical techniques, problem-solving videos, molecular structure tutorials in Jmol, Protein Data Bank IDs in Jmol, liv￾ing graphs, and online quizzes (each described un der "Additional Student Media" below). r Instructor features include the ability to add notes or files to any page and to share these notes with students. Notes may include text, Web links, animations, or photos. Instructors can also assign the entire text or a custom version of the eBook. Additional Instructor Media Instructors are provided with a comprehensive set of teaching tools, each developed to support the text, lecture presentations, and individual teaching styles. All instructor media are available for download on the book Web site (www.whfreeman.com/lehningerbe) and on the Instructor Resource CDIDVD (ISBN I-4292-1912-2). These media tools include: r Fully optimized JPEG flles of every flgure, photo, and table in the text, with enhanced color, higher resolution, and enlarged fonts. The flles have been reviewed by course instructors and tested in a large lecture hall to ensure maximum clarity and visibility. The JPEGs are also offered in separate fi.les and in PowerPoint@ format for each chapter. r The 150 most popular images in the textbook are available in an Overhead Thanspaxency Set (ISBN 1-4292-1911-4), fully optimized for maximum visibil￾ity in the lecture hall. r Animated Enzyme Mechanisms and Animated Biochemical Teehniques are available in Flash fi.les and preloaded into PowerPoint, in both PC and Macintosh formats, for lecture presentation. (See list of animation topics on the inside front cover.) r A list of Protein Data Bank IDs for the structures in the text is provided, arranged by fuure number. A new feature in this edition is an index to all struc￾tures in the Jmol interactive Web browser applet. r Living Graphs illustrate key equations from the textbook, showing the graphic results of changing parameters. r A comprehensive Test Bank in PDF and editable Word formats includes 150 multiple-choice and short-answer problems per chapter, rated by level of difflcr-rltv. Additional Student Media Students are provided with media designed to enhance their understanding of biochemical principles and im￾prove their problem-solving ability. AII student media, along with the PDB Struetures and Living Graphs, are also in the eBook, and many are available on the book Web site (www.whfreeman.com/lehningerSe). The student media include: r New Problem-Solving Videos, created by Scott Ensign of Utah State University proide24/7 online problem-solving help to students. Through a two-part approach, each 10-minute video covers a key textbook problem repre￾senting a topic that students traditionally struggle to master. Dr. Ensign first describes a proven problem￾solving strategy and then applies the strategy to the problem at hand in clear, concise steps. Students can easily pause, rewind, and review any steps as they wish until they firmly grasp not just the solution but also the reasoning behind it. Working through the problems in this way is designed to make students better and more confident at applying key strategies as they solve other textbook and exam problems. r Student versions of the Animated Enzyme Mechanisms and Animated Biochemical Techniques help students understand key mechanisms and techniques at their own pace. For a complete list of animation topics, see the inside front cover

PrefaceDiscussionQuestions:provided forDeach section;designed for individualProtein Archirecturereview,studygroups,orclassroomdiscussionASelf-Test:"Doyouknowtheterms?";crosswordpuzzles,multiple-choice,fact-driven questions;and questionsthat ask students to applytheirnewknowledgeinnewdirections-plusanswers!AcknowledgementsThis book is a team effort,and producing itwould be impossible without the outstandingpeople at w. H. Freeman and Company whosupported us at every step along the way.Randi Rossignol (SeniorEditor)andKateAhr(Executive Editor)arranged reviews, mademany helpful suggestions,encouraged us, kept us ontarget, and tried valiantly (if not always successfully) tokeep us on schedule.OuroutstandingProject Editor,LizGeller,somehowkeptthebookmovingthroughproductionin spite of our missed deadlines and last-minute changes,Molecular Structure Tutorials, using the Jmol-and did so with her usual grace and skill. We thankWebbrowserapplet,allowstudents to explore inVicki Tomaselli for developing the design,and MarshamoredepththemolecularstructuresincludedinCohenfor thebeautiful layout.Weagain had thegood for-the textbook, including:tunetoworkwithLindaStrange,asuperbcopyeditorwhoProtein Architecturehas editedall five editions of Principles of BiochemistryBacteriorhodopsin(aswellasthetwoeditions of itspredecessor,Lehninger'sLac RepressorBiochemistry).Her contributions are invaluable andNucleotidesenhancethetext wherever shetouches it.Wewere alsoMHCMoleculesagain fortunate to have the contributions and insights ofTrimeric G ProteinsMorgan Ryan, who worked with us on the third and fourthOxygen-BindingProteinseditions. We thank photo researcher Dena Digilio Betz forRestriction Endonucleasesherhelplocating images,andNickTymoczkoandWhitneyHammerhead RibozymeClench for keeping the paper and files flowing among allparticipants in the project. Our gratitude also goes toOnlineQuizzes includeapproximately20chal-Debbie Clare,AssociateDirector of Marketing,for her cre-lengingmultiple-choicequestions for eachchapter,ativity and good humor in coordinating the sales andwith automaticgrading and textreferencesandmarketingeffortfeedbackonallanswers.In Madison, Brook Soltvedt is (and has been for alltheeditionswehaveworkedon)ourfirst-lineeditorandTheAbsoluteUitimateGuidetoLehningerPrinciplesofcritic.She is thefirst to see manuscript chapters, aids inBiochemistry,FifthEdition,StudyGuideand Solutionmanuscriptandartdevelopment,ensuresinternal con-Manual,byMarcy Osgood (Universityof NewMexicosistency in content and nomenclature, and keeps us onSchool of Medicine)and Karen Ocorr(Universityoftask with more-or-less gentle prodding.As she did forCalifornia,San Diego);1-4292-1241-1thefourth edition,ShelleyLusetti,nowof NewMexicoState University, read every word of the text in proofs,TheAbsoiute,Ultimate Guide combinesan innovativecaughtnumerousmistakes,andmademanysuggestionsstudy guide with a reliable solutions manual (providingthat improved thebook.extended solutions to end-of-chapterproblems)inoneThe new art in this edition, including the new molecu-convenient volume.Thoroughly class-tested, the Studylargraphics,wasdonebyAdam Steinberg,hereinMadi-Guide includes for each chapter:son, who often made valuable suggestions that led toMajor Concepts:aroadmapthrough thechapterbetterand clearer illustrations.This edition also containsmany molecular graphics produced for the third andWhat to Review: questions that recapkeypointsfourth editions by Jean-Yves Sgro, another Madisonfromprevious chapters

Protein Archltecture Terthrv Struclurc of Largc Globula( Protlins a rdq @ dE co& dE ork srr .l@id&tu 'e tu d'nd,@b.dtu, @d tutuAalhtutvoBbE Wdtrkl.dhditrtuotuds. @^*16 tu Urr.tr dh. drud b.driffier,<fud||fun d6tud(NDtu6. Tdohr.|*M!nrdbr|frkbt Mitfrhtdbd4@q b.wd4tltui6frddndn tu{dkki*fu.drdorM r.!d{tu iltuhqffiqt@dF'tr4{U.!6 q&hr@otu.ffiddM.t,!@d Nrilerfrfrddtu.dN@d t |ME h{ Ffu.& ture&d, {q.S rb&tuMh'mu. ll ht 4 Su4ecddad klf!7 a$MdBFdhhdham @!Mdffiinsd kqhd&tu q!4h,1*.$k -d': btuMbnqm 6 MF,rhsr @ rtuFddSqtobMtub&nlmt 6.tutuWruFi!@dl@haur MabFlildKhfi*d6tu!hurdb&lE at!r. I &N.lnffirerlMrdhir h uaFrc-t.erdbbMhtuffid.di dturRh{MmMdrdBt|,fu hnh db*dn.lhh -c- b, hrkM)lFa at.* *u* " - *,*"r*i1,tJM b.h.id. h Mft 6Mh*{hddM &.dildtuSmdh. . A.d.drtuh€lrx nd.daid3 anl.wBndfr , q!tu h S r Moleeular Structure Thtorials, using the Jmol￾Web browser applet, allow students to explore in more depth the molecular structures included in the textbook, including: Protein Architecture Bacteriorhodopsin Lac Repressor Nucleotides MHC Molecules Tfimeric G Protehs Oxygen-Binding Proteins Restriction Endonucleases Hammerhead Ribozyme r Online Quizzes include approximately 20 chal￾lengrng multiple-choice questions for each chapter, with automatic grading and text references and feedback on all answers. The Absolute, Ultimate Guide to Lehninger Principles of Biochemistry, Fifth Edition, Study Guide ond Solutions Manual, by Marcy Osgood (University of New Mexico Schoolf Medicine) and Karen Ocorr (University of Ca lifornia, 5a n Diego); 1 - 4292-1241 -"1 The Absolute, Ult'imnte Guide combines an irmovative study guide with a reliable solutions manual (providing extended solutions to end-of-chapter problems) in one convenient volume. ThorougNy class-tested, the Study Guide includes for each chapter: r Major Coneepts: a roadmap through the chapter r What to Review: questions that recap key points from previous chapters Preface [.t"] Discussion Questions: provided for each section; designed for individual review, study groups, or classroom discussion A Self-Tbst: "Do you know the terms?"; crossword puzzles; multiple-choice, fact-driven questions; and questions that ask students to apply their new knowledge in new directions-plus answers! Acknowledgements This book is a team effort, and producing it would be impossible without the outstanding people at W. H. Freeman and Company who supported us at every step along the way. Randi Rossignol (Senior Editor) and l(ate Alu (Executive Editor) arranged reviews, made many helpful suggestions, encouraged us, kept us on taxget, and tried valiant$ (if not always successfully) to keep us on schedr:le. Our outstanding Project Editor, Liz Geller, somehow kept the book moving through production in spite of our missed deadlines and last-minute changes, and did so with her usual grace and skill. We thank Vicki Tomaselli for developing the design, and Marsha Cohen for the beautiful layout. We again had the good for￾tune to work with Linda Strange, a superb copy editorwho has edited all flve editions of Prirrci,plns of Binchenaistrg (as well as the two editions of its predecessor, Lehninger's Bi,ochenaistry). Her contributions are invaluable and enhance the text wherever she touches it. We were also again fortunate to have the contributions and insights of Morgan Ryan, who worked with us on the third and fourtlt editions. We thark photo researcher Dena Dgtlio Betz for her help locating images, and Nick TVmoczko and Whitney Clench for keeping the paper and files flowing among all participants in the project. Our gratitude also goes to Debbie Clare, Associate Director of Marketing, for her cre￾ativity and good humor in coordinating the sales and marketing effort. In Madison, Brook Soltvedt is (and has been for all the editions we have worked on) our first-line editor and critic. She is the first to see manuscript chapters, aids in manuscript and art development, ensures internal con￾sistency in content and nomenclature, and keeps us on task with more-or-less gentle prodding. As she did for the fourth edition, Shelley Lusetti, now of New Mexico State University, read every word of the text in proofs, caught munerous mistakes, and made many suggestions that improved the book. The new art in this edition, including the new molecu￾Iar graphics, was done by Adam Steinberg, here in Madi￾son, who often made valuable suggestions that led to better and clearer illustrations. This edition also contains many molecular graphics produced for the third and fourth editions by Jean-Yves Sgro, another Madison

xivPrefacecolleague,Wefeelveryfortunate tohave suchgifted part-Scott C.Mohr,Boston UniversityKimberlyMowry,BrowmUniversityners as Brook, Shelley, Adam, and Jean-Yves on our team.Leisha Mullins,Texas A&M UniversityWe arealsodeeplyindebtedtoBrian White oftheUni-Sewite Negash,California State Umiversity,Long BeachversityofMassachusetts-Boston,whowrotethenewAllen W.Nicholson,Temple Umiversitydataanalysis problemsat the end of eachchapter.HiroshiNikaido,Umiversity of Califormia,BerkeleyMany colleagues played a special role through theirJames Ntambi,University ofWiscomsin-Madisominterest in theproject and their timely input.ProminentTimothyF.Osborne,Umiversityof Califormia,Irvineamong these are Laurens Anderson of the UniversityJoseR.Perez-Castineira, Umiversity of Seville, Spainof Wisconsin-Madison;JeffreyD.Esko of theUniversity ofTerryPlatt, University of RochesterWendyPogozelski, State University of New York at GeneseoCalifornia, San Diego; JackKirsch and his students atJonathanPopper,University of Wiscomsin-Madisonthe University of California, Berkeley;and Dana Aswad,Thomas Poulos,University of California, IrvineShiou-Chuan (Sheryl) Tsai,Michael G. Cumsky,andJackPreiss,Michigan StateUniversitytheir colleagues (listed below)at the University ofAnna Radominska-Pandya,Universityof ArkansasCalifornia, Irvine. Many others helped us shape this fifthRon Raines,University of Wiscomsin-Madisoneditionwiththeircomments,suggestions,andcriticisms.Tom A.Rapoport,Harvard Medical SchoolToall of them,weare deeplygrateful:Jason J.Reddick, University ofNorth Carolina, GreensboroMaryRoberts,BostomCollegeIngridK.Ruf, University of California,IrvineRichard M. Amasino, University of Wisconsin-MadisomAboozar Soleimani,Tehran Umiversity, IranLouise E. Anderson, University of luinois at ChicagoMark Spaller,Wayme State UniversityCheryl Bailey,University of Nebraska,LinconStephen Spiro, University of Teras at DallasKennethBalazovich,University of MichiganNarasimha Sreerama, Colorado State UmiversityThomas O.Baldwin,University ofArizonaJonD.Stewart,University ofFloridaVahe Bandarian, University of ArizonaKoni Stone,California State Umiversity, StanislausEugene Barber, University of RochesterJon R.Stultzfus,Michigan StateUniversitySebastian Y.Bednarek,University of Wisconsin-MadisonJeremyThorner, University of California, BerkeleyRamachandraBhat,Lincoln UniversityDean R.Tolan, Bostom UniversityJamesBlankenship,Cornell UniversitySandra L.Turchi,Millersville UmiversitySandra J.Bonetti,Colorado StateUniversity,PuebloBarbara Bowman, University of California, BerkeleyManuelVarela,EasternNewMerico UniversityScottD.Briggs,Purdue UniversityBobWarburton,ShepherdUniversityTracyWare, Salem State CollegeJeffBrodskyUniversityofPittburSusan Weintraub,University of Texas, Health Science CenterBen Caldwell,Missouri Western StateUniversityMichael Yaffe,Massachusetts Institute of TechnologyDavid Camerini,University of California, IrvineGuillaume Chanfreau, University of California, Los AngelesMelanie Cocco,University of California,IrvineWe lack the space here to acknowledge all the otherJeffrey Cohlberg, California State University, Long Beachindividuals whose special efforts went into this book.KimD.Collins,UniversityofMarylandWe offer instead our sincere thanks-and the finishedCharles T.Dameron,Duquesne Universitybook that they helped guide to completion. We, ofRichard S.Eisenstein,Universityof Wisconsin-Madisoncourse, assumefull responsibility for errors of fact orGerald W.Feigenson, Cornell Umiversityemphasis.RobertH.Fillingame,University of Wisconsin-MadisonWe want especially to thank our students at theBrian Fox,University of Wiscomsin-MadisonUniversity of Wisconsin-Madison for their numerous com-Gerald D.Frenkel, Rutgers UniversityPerry Frey,University of Wisconsin-Madisomments and suggestions. If something in the book does notDavid E.Graham,University of Texas-Austinwork, they are never shy about letting us know it.We areWilliamJ.Grimes,UmiversityofArizomagrateful to the students and staff of our researchgroups andMartynGunn,TexasA&MUniversityoftheCenterforBiologyEducation,whohelpedusbalanceOlivia Hanson,University of Central Oklahomathe competingdemands onourtime;to our colleagues inAmy Hark,Muhlenberg Collegethe Department of Biochemistry at the University ofShaunV.Hernandez,University ofWisconsin-MadisonWisconsin-Madison,who helped us with advice and criticism;PeterHinkle,Cornell Universityandto the many students and teachers who havewrittentoP.Shing Ho,Oregon State Umiversitysuggestways of improving thebook.WehopeourreadersCharles G.Hoogstraten,Michigan State Universitywill continue to provideinput forfutureeditions.GerwaldJogl,BrownUniversitySir Hans Kornberg,Boston UmiversityFinally, we express our deepest appreciation to ourBobLandick,Universityof Wisconsin-Madisomwives, Brook and Beth, and our families, who showedPatrick D. Larkin, Texas A&M University, Corpus Christiextraordinary patience with, and support for, our bookRyan P.Liegel,University of Wisconsin-Madisonwriting.Maria Linder,California State University,FullertomAndy C.LiWang,TexasA&MUniversityDavid L. NelsonJohn Makemson,Florida International UniversityMichaelM.CoxJohnC.Matthews,University ofMississippi,SchoolofPharmacyMadison,WisconsinBenjamin J.McFarland,SeattlePacificUmiversityAnant Menon, Weill Cornell Medical CollegeJanuary2008Sabeeha Merchant,University of California,Los Angeles

colleague. We feel very fortunate to have such gifted part￾ners as Brook, Shelley, Adam, and Jean-Yves on our team. We are also deeply indebted to Brian White of the Uni￾versity of Massachusetts-Boston, who wrote the new data analysis problems at the end of each chapter. Many colleagues played a special role through their interest in the project and their timely input. Prominent among these are Laurens Arderson of the University of Wisconsin-Madison; Jeffrey D. Esko of the University of California, San Diego; Jack Kirsch and his students at the University of California, Berkeley; and Dana Aswad, Shiou-Chuan (Sheryl) Tsai, Michael G. Cumsky, and their colleagues (listed below) at the University of California, Irvine. Many others helped us shape this ffih edition with their comments, suggestions, and criticisms. To all of them, we are deeply grateful: Richard M. Amasino, Uniu ersitg oJ Wi,sconsi,n-M adison Louise E. Anderson, Uni,uersi,ty of lllinoi,s at Cltdcago Cheryl Bailey, Uni,uersi,tg of Nebraskq Li,ncoln Kenneth Balazovich, Uni,uersi,tg oJ Mi,chi,gon Thomas O. Baldwin, Uni,uersitg of Ari,zona Vahe Bandari an, Uniu ersitg oJ Adzona Eugene Barber, Uni,uersi,tg of Rochester Sebastian Y Bednarek, Uni,u ersi,tg oJ Wisconsi,n-M udi,son Ramachandra Bhal, Lincoln Uniuersity James Blankenship, CorneII Uni,uersi,ty Sandra J. Bonetti, Colorado State [Jniuersitg, Pueblo Barbara Bowman, Uni,uersi,ty oJ CaliJorni,a, Berkeley Scott D. Briggs, Purdue Uniuersi,ty Jeff Brodsky, Uni,uersi,tg of Pi,ttsburgh Ben Caldwell, Mi,ssouri Westerru State Uniuersi,ty David Camerini, Uniuers'itg oJ CaliJorni,a, Irui,ne Guillaume Chanfreau, Uni,uersity oJ Cali,Jorni,a, Los Angeles Melanie Cocco, Uni,uersitg oJ Cali,Jontia, Irui,ne Jeffrey Cohlberg, CaliJorni,a Stute [Jniuersi,tg, Lotzg Beach Kim D. Collins, Uniuersi,tg of Marytand Charles T. Dameron, Duquesne Uni,uersi,ty Richard S. Eisenstein, Uni,uersi,tg oJ Wisconsi,n-Mad,i,son Gerald W. Feigenson, CorneLL Uni,uersi,ty Robert H. Fillingame, Uni,uersi,tg oJ Wisconsin-Madisota Brian Fox, Uni,u ersi,ty oJ Wisconsin-M adi,son Gerald D. Frenkel, Rutgers {Jni,uersi,tg Perry Frey, Uni,uersi,tg oJ Wi,sconsin-M adi,son David E. Graham, Uni,uersi,tg oJ Teras-Austin William J. Grimes, Uni,uersi,ty of Ari,zona Mart}'n Gurn, Teras A&M Uni,uersitg Olivia Hanson, Uni,uersi,ty oJ Central Oklahoma Amy Hark, Muh,Ienberg CoILege Shaun V. Hernandez, Uni,uersi,tg oJ Wi,sconsi,n-Madison Peter Hinkle, Conwll Uniuersi,tg P. Shing Ho, Oregon State Uni,uersi,tA Charles G. Hoogstraten, Mi,chigan State Uni,uersi,tA Gerwald Jogl, Brown Uniuersitg Sir Hans Kornberg, Boston Uni,uersity Bob Landick, Uni,uersi,tg oJ Wi,sconsin-Mad,ison Patrick D. Larkin, Teras A&M Uni,uersi,ty, Corptn Christi, Ryan P. LiegeI, Uniuersitg oJ Wi,sconsin-Madi,son Maria Lhder, Cali,forni,a State Uni,uersi,tg, Fullerton Andy C. LiWang, Teras A&A,[ Uni,uersitg Johr Makems on, Florida Internati,onal [lni,uersi,tg John C. Matthews, UiriDersifu of MississzWt, Schno| oJPha,rmang Benjamin J. McFarland, Seattle Pacifi,c Uni,uersi,ty Anant Menon, Wei,LL CorneII Medi,cal CoILege Sabeeha Merchant, Uni,uersi,tg oJ Cali,fotnia, Los Angeles Scott C. Mohr, Boston Uni,uersi,tg Kimberly Mowry, Brown Uniuersi,ty Leisha Mullins, Teras A&M Uni,uersi,tg Sewite Negash, Cali,Jorni,a State Uni,uersi,ty, Long Beach Allen W Nicholson, Temple Uni,uersi,ty Hiroshi Nikaido, Uni,uersitg of CaliJorni,a, Berkeley James Ntambi, Uni,uersi,tg oJ Wisconsi,n-Madi,son Timothy F. Osborne, Uni,uersi,tg of Cali,Jornia, Iyai,ne Jos6 R. P6rez-Castifleira, Uni,uersi,tg oJ Seui,lle, Spai,n Terry Platt, Uni,uersi,tg of Rochester Wendy Pogozelski, State Uni,uersitg oJ New York at Geneseo Jonathan Popper, Uni,uersi,tg oJ Wi,sconsi,n -Modi,son Thomas Poulos, Uniuersi,tg oJ CaliJorn'i,a, Irui,ne Jack Preiss, Mi,chi,ga.ll Sta,te Uniuersi,W Arma Radominska-Pandya, Uni,uersi,tg oJ Arkansas Ron Raines, Uni,uersi,tg oJ Wi,scon si,n-Madi,son Tom A. Rapoport, Harvard Medi,ca| School Jason J. Reddick, Uni,uersi,tg oJ North Caroli,na, Greensboro Mary Roberts, Boston College Ingrid K. Rttf, Uni,uersi,ty oJ Cali,forni,a, Irui,ne Aboozar Soleimani, Tehran Uni,uersi,tg, Iran Mark Spaller, Wayne Sta,te Uni,uersi,tA Stephen Spiro, Uniuersitg oJ Teras at DaILo,s Narasimha Sreerama, C olorado State Uni,u ersi,ty Jon D. Stewart, Uni,uersi,ty of Florida Koni Stone, CaliJotni.a State Uni,uersitA, Stanislo,us Jon R. Stultzfus, Mi,chigan State Uni,uersi,tg Jeremy Thorner, Uni,uersi,tg of Cali,forni,a, Berkeleg Dean R. ToIan, Boston Uni,uersi,ty Sandra L. Tirrchi, Mi,Ilersui,Ile Uni,u ersi,tg Manuel Varela, Eastern New Meni,co Uni,uersi,tg Bob Warburton, SheTsherd Uni,uersi,ty Ttacy Ware, Salem State CoLIege Susan Weintraub, Unintersi,tg oJ Teras, Health Sci,ence Csttter Michael Yaffe, Massachusetts Insti,tute of Technologg We lack the space here to acknowledge all the other individuals whose special efforts went into this book. We offer instead our sincere thanks-and the finished book that they helped guide to completion. We, of course, assume full responsibility for errors of fact or emphasis. We want especially to thank our students at the University of Wisconsin-Madison for their nunerous com￾ments and su ggestions. If something in the book does not work, they are never shy about letting us lcrow it. We are gratefirl to the students and staff of our research groups and of the Center for Biologz Education, who helped us balance the competing demands on our time; to our colleagues in the Department of Biochemistry at the University of Wiscorsin-Madison, who helped us with advice and criticism; and to the marry students and teachers who have written to suggest ways of improving the book. We hope our readers will continue to provide input for future editions. Finally, we express our deepest appreciation to our wives, Brook and Beth, and our families, who showed extraordinary patience with, and support for, our book writing. David L. Nelson Michael M. Cox Madison, Wisconsin January 2008