Solution Manual Student Companion F U N D A M E N T A L S O F Biochemistry Life At The Molecular Level Voet Voet Pratt F O U R T H E D I T I O N

STUDENT COMPANION F U N D A M E N T A L S O F Biochemistry LIFE AT THE MOLECULAR LEVEL Voet Voet Pratt F O U R T H E D I T I O N Akif Uzman Jerry Johnson Joseph Eichberg William Widger Donald Voet Judith G. Voet Charlotte W. Pratt This page is intentionally left blank STUDENT COMPANION TO ACCOMPANY FUNDAMENTALS OF BIOCHEMISTRY LIFE AT THE MOLECULAR LEVEL Fourth Edition Akif Uzman University of Houston Jerry Johnson University of Houston Joseph Eichberg University of Houston William Widger University of Houston Donald Voet University of Pennsylvania Judith G. Voet Swarthmore College Charlotte W. Pratt Seattle, Washington JOHN WILEY & SONS, INC Cover Designer Madelyn Lesure Cover Illustration Norm Christiansen Cover Photos (Vitruvian Man): © Odysseus/Alamy and © Dennis Hallinan/Alamy Molecular structures clockwise from top: based on X-ray structures that were respectively determined by Richard Dickerson and Horace Drew, Caltech; Gerard Bunick, University of Tennessee; Thomas Steitz, Yale University; Alfonso Mondragón, Northwestern University; Venki Ramakrishnan, MRC Laboratory of Molecular Biology, Cambridge, U.K.; Andrew Leslie and John Walker, MRC Laboratory of Molecular Biology, Cambridge, U.K. Founded in 1807, John Wiley & Sons, Inc. has been a valued source of knowledge and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Our company is built on a foundation of principles that include responsibility to the communities we serve and where we live and work. 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Student Companion (paperback) ISBN--3 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 Contents 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Introduction to the Chemistry of Life Water Nucleotides, Nucleic Acids, and Genetic Information Amino Acids Proteins: Primary Structure Proteins: Three-Dimensional Structure Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies Carbohydrates Lipids and Biological Membranes Membrane Transport Enzymatic Catalysis Enzyme Kinetics, Inhibition, and Control Biochemical Signaling Introduction to Metabolism Glucose Catabolism Glycogen Metabolism and Gluconeogenesis Citric Acid Cycle Electron Transport and Oxidative Phosphorylation 1 9 21 29 40 49 60 72 80 90 96 108 121 128 137 146 154 160 19 20 21 22 23 24 25 26 27 28 Photosynthesis Lipid Metabolism Amino Acid Metabolism Mammalian Fuel Metabolism: Integration and Regulation Nucleotide Metabolism Nucleic Acid Structure DNA Replication, Repair, and Recombination Transcription and RNA Processing Protein Synthesis Regulation of Gene Expression Answers to Questions Solutions to Problems 169 176 188 197 203 210 219 230 238 247 AQ-1 SP-1 Welcome to biochemistry! You are about to become acquainted with one of the most exciting scientific disciplines. The biotechnology industry, with its roots in molecular genetics, is one of the most visible manifestations of the explosion of biochemical knowledge that has occurred during our lifetime. Drug design and novel approaches such as gene therapy rely on the fundamental knowledge of the chemistry of biological molecules, particularly proteins. Our most common diseases (e.g., diabetes and heart disease) have pleiotropic multifaceted physiological effects that are best understood in terms of biochemistry. You will soon discover that biochemistry’s impact on our lives cannot be over-emphasized. We are excited to bring you an ever-expanding understanding of this magnificent subject! Learning biochemistry is not easy but it can be fun! Most students discover that biochemistry is a synthetic science, merging knowledge of general chemistry, organic chemistry, and biology. Hence, a more mature and creative kind of thinking is required to gain a deep understanding of biochemistry. In addition to a solid foundation in chemistry and biology, you will need to recognize and assimilate some general principles from other disciplines within biology, including physiology, genetics, and cell biology. In this respect, biochemistry is not all that different from nonscientific pursuits that require some degree of “lateral thinking” across disciplines. This Student Companion accompanies Fundamentals of Biochemistry Fourth Edition by Donald Voet, Judith G. Voet, and Charlotte W. Pratt. It is designed to help you master the basic concepts and exercise your analytical skills as you work your way through the textbook. Each chapter of the Student Companion is divided into four parts, beginning with a general summary reminding you of the topics covered in that chapter. This is followed by a section called Essential Concepts, which provides an overview of the main facts and ideas that are essential for your understanding of biochemistry. This can be regarded as a set of brief notes for each chapter, alerting you to the key facts you need to commit to memory and to the concepts you need to master. You will soon notice that biochemical knowledge is cumulative: new concepts often rely on a solid understanding of previously presented concepts. Hence, one of the key goals of this Companion is to help you gain this understanding. The third and last section is the Questions. These are organized in a manner to help you gain a firm understanding of each section of a chapter. Some questions ask you to recall essential facts while others exercise your problem-solving skills. Answers to all of the questions are provided at the end of the Student Companion. However, you do yourself a great disservice by turning to them too soon. Don’t know the answer right away? Keep trying! Go back to the text to find clues for yourself. Use the answers to check yours, not to fill in a temporary void in your understanding. The Solutions to all end of chapter problems in the text can be found after the Answers to Questions. As a new addition to this edition of the Student Companion, we have added three new features to select chapters: Behind the Equations, Calculation Analogies and Play It Forward. Behind the Equations is a section that tackles key equations in Biochemistry. This section will provide insights and learning strategies for using and understanding what these equations are really telling us, and how to use them intuitively. The Calculation Analogies section will tackle key equations conceptually using simple analogies that will help students understand how to solve problems. The Play It Forward Section will take critical concepts from early chapters and integrate them into material in later chapters to help students see how the content continues to build upon itself, hopefully allowing students to synthesize Biochemistry as a discipline. “How should I study biochemistry beyond reading the textbook and working in this Companion?” is a likely question from students. The phrase, “if you don’t use it, you lose it” applies here. It is pointless to simply read your biochemistry textbook over and over. Unless you are actively engaged in working with the material, you become a passive reader. Active engagement includes using your hands to work problems, drawing pictures, or writing an outline or flow chart. As you read, ask yourself questions and seek answers from your text and your instructor. By doing these things, you use the material, and it becomes more efficiently transferred to your long-term memory. “How often should I study biochemistry?” is also a common question. Most instructors agree that frequent short study sessions—even daily—will pay greater dividends than a single long session once a week. Because short-term memory lasts just a few minutes, take a few minutes after every class to review your notes. Similarly, stop reading your text, and review on paper with diagrams, word charts, flow diagrams, what you just read. Talk biochemistry with anyone who will listen. Form a study group to enrich your knowledge and test your memory. All these activities will result in the transfer of knowledge from short-term memory to long- term memory. In other words, the more you use biochemistry, the better you know it and the more fun you will have with it. One of the truly most satisfying ways to learn biochemistry is to apply its principles and findings to problems that integrate your knowledge. To this end, Dr. Kathleen Cornely has developed numerous case studies that test your analytical the skills. You will find these case studies on the Fundamentals of Biochemistry 4e Student Companion Site at in Fundamentals of Biochemistry 4e WileyPLUS course (). Topics for the case studies were chosen to cover a range of interesting areas relevant to biochemistry. The cases themselves are based on data from research reports as well as clinical studies. The prerequisites include material that you are likely to be studying in biochemistry class, but occasionally include concepts from genetics and immunology on a level likely to be encountered in a first-year general biology course. The answers to the questions posed in these case studies can be obtained from your instructor. We have many people to thank for helping us get this Companion to you. First and foremost, we would like to acknowledge Associate Editor, Ms. Aly Rentrop, and Production Editor, Ms. Sandra Dumas. In addition, we would like to acknowledge Ms. Petra Recter, Associate Publisher for Physics and Chemistry at John Wiley and Sons for her support of this project. We are also indebted to Caroline Breitenberger of The Ohio State University and Laura Mitchell of St. Joseph’s University for their much-appreciated reviews of our original draft. We would also like to thank our students at Swarthmore College, the University of Houston, and the University of Houston-Downtown for pointing out errors and ambiguities in earlier drafts of this work. It is still possible that errors persist, and so we would greatly appreciate being alerted to them. Please forward you comments to Akif Uzman (). Akif Uzman Jerry Johnson Joseph Eichberg William Widger Charlotte W. Pratt Donald Voet Judith G. Voet This page is intentionally left blank 1 Introduction to the Chemistry of Life This pchapter pintroduces pyou pto plife pat pthe pbiochemical pand pcellular plevel. pIt pbegins pwith pa pdiscussion pof pthe pchemical porigins pof plife pand pits pearly pevolution. pThis pdiscussion pcontinues pinto pideas pand ptheories pabout pthe pevolution pof porganisms, pfollowed pby pa pbrief pintroduction p to ptaxonomy pand pphylogeny pviewed pfrom pa pmolecular pperspective. pThe pchapter pconcludes pwith pan pintroduction pto pthe pbasic pconcepts pof pthermodynamics pand pits papplication pto pliving psystems. pBiochemistry, plike pall pother psciences, pis pa pbased pon pthe pmeasurement pof pobservable pphenomena. pHence, pit pis pimportant pto pbecome pfamiliar pwith pthe pconventions pused pto pmeasure penergy pand pmass. pBox p1-2 ppresents pthe pessential pbiochemical pconventions pthat pwe pwill pencounter pthroughout pFundamentals pof pBiochemistry. Essential pConcepts The pOrigin pof pLife 1. 2. 3. 4. 5. 6. Living pmatter pconsists pof pa prelatively psmall pnumber pof pelements, pof pwhich pC, pN, pO, pH, pCa, pP, pK, pand pS paccount pfor p~98% pof pthe pdry pweight pof pmost porganisms p(which pare p70% pwater). pThese pelements pform pa pvariety pof preactive pfunctional pgroups pthat pparticipate pin pbiological pstructure pand pbiochemical preactions. The pcurrent pmodel pfor pthe porigin pof plife pproposes pthat porganisms parose pfrom pthe ppolymerization pof psimple porganic pmolecules pto pform pmore pcomplex pmolecules, psome pof pwhich pwere pcapable pof pself-replication. Most ppolymerization preactions pinvolving pthe pbuilding pof psmall porganic pmolecules p into plarger pmore pcomplex pones poccur pby pthe pformation pof pwater. pThis pis pcalled pa pcondensation preaction. A pkey pdevelopment pin pthe porigin pof plife pwas pthe pformation pof pa pmembrane pthat pcould pseparate pthe pcritical pmolecules prequired pfor preplication pand penergy pcapture pfrom p a ppotentially pdegradative penvironment. Complementary psurfaces pof pmolecules pand pmacromolecules pprovide pa ptemplate pfor pbiological pspecificity p(e.g., pmacromolecular passembly, penzyme pactivity, pand pexpression pand preplication pof pthe pgenome). Modern pcells pcan pbe pclassified pas peither pprokaryotic por peukaryotic. pEukaryotic pcells pare pdistinguished pby pa pvariety pof pmembrane-bounded porganelles pand pan pextensive pcytoskeleton. 2 Chapter 1 Introduction to the Chemistry of Life Organismal pEvolution 7. 8. 9. Prokaryotes pshow pa plimited prange pof pmorphologies pbut pvery pdiverse pmetabolic pcapabilities. Phylogenetic pevidence pbased pon pcomparisons pof pribosomal pRNA pgenes phave pbeen pused pby pWoese pand pcolleagues pto pgroup pall porganisms pinto pthree pdomains: parchaea, pbacteria, pand peukarya. The pevolution pof psexual preproduction pmarks pan pimportant pstep pof pthe pevolution p of porganisms, pbecause pit pallows pfor pgenetic pexchanges pthat plead pto pan pincrease pin pthe padaptability pof pa ppopulation pof porganisms pto pchanging penvironments. 10. Eukaryotes pcontain pseveral pmembrane-bounded pstructures, psuch pas pmitochondria pand pchloroplasts, pwhich pmay pbe pdescended pfrom pancient psymbionts. 11. Archaea prepresent pa pthird pdomain por pbranch pof plife pin pthe pthree-domain psystem pof pclassification. pWhile pthey poutwardly presemble pbacteria, ptheir pgenomes pand pthe pproteins pencoded pin pthem pmore pclosely presemble pthose pof peukaryotes. 12. Biological pevolution pis pnot pgoal-directed, prequires psome pbuilt-in psloppiness, pis pconstrained pby pits ppast, pand pis pongoing. 13. Natural pselection pdirects pthe pevolution pof pspecies. Thermodynamics 14. The pfirst plaw pof pthermodynamics pstates pthat penergy p(U) pis pconserved; pit pcan pneither pbe pcreated pnor pdestroyed. 15. Enthalpy p(H) pis pa pthermodynamic pfunction pthat pis pa psum pof pthe penergy pof pthe psystem pand pthe pproduct pof pthe ppressure pand pthe pvolume p(PV). pSince pbiochemical pprocesses poccur pat pconstant ppressure pand phave pnegligible pchanges pin pvolume, pthe pchange pof penergy pof pthe psystem pis pnearly pequivalent pto pthe pchange pin penthalpy p(U p≈ pH). 16. The psecond plaw pof pthermodynamics pstates pthat pspontaneous pprocesses pare pcharacterized pby pan pincrease pin pthe pentropy pof pthe puniverse, pthat pis, pby pthe pconversion pof porder pto pdisorder. 17. The pspontaneity pof pa pprocess pis pdetermined pby pits pfree penergy pchange p(G p= pH p– pTS). pSpontaneous preactions phave pG p p0 p(exergonic) pand pnonspontaneous preactions phave pG p p0 p(endergonic). 15. pFor pany pprocess pat pequilibrium, pthe prate pof pthe pforward preaction pis pequal pto pthe prate pof pthe preverse preaction, pand pG p= p0. 18. Energy, penthalpy, pentropy, pand pfree penergy pare pstate pfunctions; pthat pis, pthey pdepend ponly pon pthe pstate pof pthe psystem, pnot pits phistory. pHence, pthey pcan pbe pmeasured pby pconsidering ponly pthe pinitial pand pfinal pstates pof pthe psystem pand pignoring pthe ppath pby pwhich pthe psystem preached pits pfinal pstate. Chapter 1 Introduction to the Chemistry of Life 3 19. The pentropy pof pa psolute pvaries pwith pconcentration; ptherefore, pso pdoes pits pfree penergy. pThe pfree penergy pchange pof pa pchemical preaction pdepends pon pthe pconcentration pof pboth p its preactants pand pits pproducts. 20. For pthe pgeneral preaction aA p+ pbB cC p+ pdD the pfree penergy pchange pis pgiven pby pthe pfollowing prelationship: 21. The pequilibrium pconstant pof pa pchemical preaction pis prelated pto pthe pstandard pfree penergy pof pthe preaction pwhen pthe preaction pis pat pequilibrium p(G p= p0) pas pfollows: G p= p–RT pln pKeq where pKeq pis pthe pequilibrium pconstant pof pthe preaction: The pequilibrium pconstant pcan ptherefore pbe pcalculated pfrom pstandard pfree penergy pdata p and vice pversa. 22. The pequilibrium pconstant pvaries pwith ptemperature pby pthe prelationship: where pH° pand pS° prepresent penthalpy pand pentropy pin pthe pstandard pstate. pA pplot p of pKeq versus p1/T, pknown pas pa pvan’t pHoff pplot, ppermits pthe pvalues pof pH° pand pS° p(and ptherefore G° pat pany ptemperature) pto pbe pdetermined pfrom pmeasurements pof pKeq pat ptwo p(or p more) ptemperatures. 23. The pbiochemical pstandard pstate pis pdefined pas pfollows: pThe ptemperature pis p25°C, pthe ppH pis p7.0, pand pthe ppressure pis p1 patm. pThe pactivities pof preactants pand pproducts pare ptaken pto pbe pthe ptotal pactivities pof pall ptheir pionic pspecies, pexcept pfor pwater, pwhich pis passigned pan pactivity pof p1. p[H+] pis palso passigned pan pactivity pof p1 pat pthe pphysiologically prelevant ppH pof p7. pThese pconditions pare pdifferent pthan pthe pchemical pstandard pstate, pso pthat pthe pbiochemical pstandard pfree penergy pis pdesignated pas pG° pand pin pthe pchemical pstandard pstate pis pG°. pWe p assume pthat pactivity pequals pmolarity pfor pdilute psolutions. 4 Chapter 1 Introduction to the Chemistry of Life 24. An pisolated psystem pcannot pexchange pmatter por penergy pwith pits psurroundings. pA pclosed psystem pcan pexchange ponly penergy pwith pits psurroundings. pA pclosed psystem pinevitably preaches pequilibrium. pOpen psystems pexchange pboth pmatter pand penergy pwith ptheir psurroundings pand ptherefore pcannot pbe pat pequilibrium. pLiving porganisms pmust pexchange pboth pmatter p and penergy pwith ptheir psurroundings pand pare pthus popen psystems. pLiving porganisms ptend pto pmaintain pa pconstant pflow pof pmatter pand penergy, preferred pto pas pthe psteady pstate. 25. Living psystems pcan prespond pto pslight pperturbations pfrom pthe psteady pstate pto prestore pthe psystem pback pto pthe psteady pstate. 26. The precovery pof pfree penergy pfrom pa pbiochemical pprocess pis pnever ptotal, pand psome penergy pis plost pto pthe psurroundings pas pheat. pHence, pwhile pthe psystem pbecomes pmore pordered, pthe psurroundings pexperience pan pincrease pin pentropy. 27. Enzymes paccelerate pthe prate pat pwhich pa pbiochemical pprocess preaches pequilibrium. pThey paccomplish pthis pby pinteracting pwith preactants pand pproducts pto pprovide pa pmore penergetically pfavorable ppathway pfor pthe pbiochemical pprocess pto ptake pplace. Key pEquations