Preface xxxili Critical Developments in Biochemistry essays emphasize and historical advances in the field 。Human biochemist emphasize the central role of basic biochemistry in medi cine and the health sciences these essays often present clinically important issues such as diet.diabetes and cardiovascular health. A Deeper Look essays expand on the text.highlighting selected topics or experimental observations. Laboratory Technig The e nental nature of biochemistry is highlighted.and a list of laboratory techniques found in this book can be seen on page xxx. Highlights of This Editior particularly those described in this text.Each structure is presented asa"Mole cula LLC in La c g program d ted oped by Mo the Unive of Vire structures with rich vivid state of-the-art graphics accompanied by a scrint tha highlights pertinent structure-function correlations Hyperlinks in the text window of each entry contr the graph ay and prese a varety of perspectives a nd function inat these molecular documents Recent Advances Highlighted in These Chapters Chapter6The higher-order structure of proteins A Deeper Look Chapter 1 The foundations of biochemistry.New highlight:The ary units of three-dimen eukaryotic cell likely emerged from an arch eal lineage.Contem comp or b which exist as an ensemble of structures of similar energies and stabilities A new"Human Biochemistry"box on chimeric antigen chemistry feature on synthetic life the chemical synthesis of a receptor(CAR)T-cel therapies as the basis of novel c cer trea bacterial genome and its incorporation into host cells to create and a nev the first organism with a fully synthetic genome. ordered proteins Chapter 2This chapter reviews the properties of water,the nature of hydrophobic interactions. bohydrates s Th weak acids,the concept of pH.and th try of c ouner systems in gal")triggers red meat allergy.A new"A Deeper Look"box on the Chapte r 3Thi apter features a simplified,morestud chemistry of cellulose crosslinks in wrinkle-free fabrics,and a new er Look" free energy changes under celular conditions standard-state free Chapter 8 The structure and chemistry of lipids A new Deeper energy changes(AG).and the situation at equilibrium(AG =0). Chapter 4 The structure and chemistry of amino acids.An intro 4。 duction to the Brainbow technique that enables labeling of many individual neurons.New A Deeper Look box on the unu feature on the endocannabinoid signalin Dno acid soluble signals such as anandamide and 2-arachidonoylglycerol.The an y ho signaling effects of sphingosine-1-phosphate. amino acids into proteins Chanter 9 Membrane structure and function A newy Humar Chapter 5 Protein Biochemistry feature on development of inhibitors of oteins as the a nts of bio. V-myristoyltransferase in brucel,the organism that cause logical function.A new section defining the cond cept of the proteome and what new insights emerge from such large-scale and the structures and functions of snarf nroteins and channe global studies of all the proteins in a given cell or tissu The pro tion of what a particular cell is doing at proteins.Five new end-of-chapter problems based on recent research on membrane proteins and transport sytems
Preface xxxiii ●● Critical Developments in Biochemistry essays emphasize recent and historical advances in the field. ●● Human Biochemistry essays emphasize the central role of basic biochemistry in medicine and the health sciences. These essays often present clinically important issues such as diet, diabetes, and cardiovascular health. ●● A Deeper Look essays expand on the text, highlighting selected topics or experimental observations. ●● Laboratory Techniques The experimental nature of biochemistry is highlighted, and a list of laboratory techniques found in this book can be seen on page xxx. Highlights of This Edition ●● ActiveModels Library of Proteins and Nucleic Acids is an optional online resource (http://www.psafe.us) for exploration of over 1,000 protein and nucleic acid structures, particularly those described in this text. Each structure is presented as a “Molecular Document” using the ICM Browser Pro modeling program developed by Molsoft, LLC in La Jolla, CA. These molecular documents were created by undergraduate biochemistry students at the University of Virginia and illustrate macromolecular structures with rich, vivid, state-of-the-art graphics accompanied by a script that highlights pertinent structure-function correlations. Hyperlinks in the text window of each entry control the graphic display and present a variety of perspectives and features for each protein or nucleic acid. A number of end-of-chapter problems challenge students to explore macromolecular structure and function through examination of these molecular documents. Recent Advances Highlighted in These Chapters Chapter 1 The foundations of biochemistry. New highlight: The eukaryotic cell likely emerged from an archaeal lineage. Contemporary eukaryotic cells are composites that harbor bacterial and archaeal contributions. A new Critical Developments in Biochemistry feature on synthetic life: the chemical synthesis of a bacterial genome and its incorporation into host cells to create the first organism with a fully synthetic genome. Chapter 2 This chapter reviews the properties of water, the nature of hydrophobic interactions, ionic equilibria, the behavior of weak acids, the concept of pH, and the major buffer systems in organisms. Chapter 3 This chapter features a simplified, more student-accessible presentation of the basic concepts of thermodynamics, highlighted by a new “A Deeper Look” box stressing the difference between free energy changes under cellular conditions, standard-state free energy changes (G), and the situation at equilibrium (G 0). Chapter 4 The structure and chemistry of amino acids. An introduction to the Brainbow technique that enables labeling of many individual neurons. New A Deeper Look box on the unusual amino acid selenocysteine and selenoproteins, and a new Critical Developments in Biochemistry box on incorporation of unnatural amino acids into proteins. Chapter 5 Proteins as polymers of amino acids; proteins as macromolecules of elaborate structure; proteins as the agents of biological function. A new section defining the concept of the proteome and what new insights emerge from such large-scale, global studies of all the proteins in a given cell or tissue. The proteome is an excellent reflection of what a particular cell is doing at a specific moment in time. Chapter 6 The higher-order structure of proteins. A Deeper Look feature on protein sectors—evolutionary units of three-dimensional structure, and a new Deeper Look feature on metamorphic proteins, which exist as an ensemble of structures of similar energies and stabilities. A new “Human Biochemistry” box on chimeric antigen receptor (CAR) T-cell therapies as the basis of novel cancer treatments, and a new “A Deeper Look” box on friction in the protein folding process, as well as expanded coverage of intrinsically disordered proteins. Chapter 7 The structure and chemistry of carbohydrates. The discovery that the disaccharide galactose-α-1,3-galactose (“alpha gal”) triggers red meat allergy. A new “A Deeper Look” box on the chemistry of cellulose crosslinks in wrinkle-free fabrics, and a new “A Deeper Look” box on the role of N-linked oligosaccharides in protein folding. Chapter 8 The structure and chemistry of lipids. A new Deeper Look feature on glycophospholipids that play a role in formation of plasma membrane signaling microdomains involved in cellular differentiation and maturation. Also a new Human Biochemistry feature on the endocannabinoid signaling system that involves lipidsoluble signals such as anandamide and 2-arachidonoylglycerol. The signaling effects of sphingosine-1-phosphate. Chapter 9 Membrane structure and function. A new Human Biochemistry feature on development of inhibitors of N-myristoyltransferase in T. brucei, the organism that causes sleeping sickness in Africa. Also revised discussions of the roles of sphingolipid and cholesterol in the formation of membrane rafts and the structures and functions of SNARE proteins and channel proteins. Five new end-of-chapter problems based on recent research on membrane proteins and transport sytems. Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
Preface at halting infection.An updated introduction to Chapter 18 Glycolysis.A Critical Developments in Biochemistry that de oce sensor that rec and Chapter 11 The structure of nucleic acids and chromosomes.An pathway that results in glucose-induced insulin secretion.New overview of the next-generation DNA sequencing technologies information on protein kinase M2(PK M2),including its newly- to sequence single molecu d pro otein kinase activity,its stimulation by S ICAR( ability to carry out low-cost sequencing of an individual's genome and the implications of the information obtained on the diagnosis of dietary fructose in the liver.and its implic and treatment of disease.Also,creation of DNA molecules com tance.metabolic syndrome.and obesity. ed of not just two,but three base pairs opens Chapter 19 The citric acid cycle A new discussion of the structure of p uvate dehydrogenase comple:a new Deeper Look feature on structure'give insights into the long mysterious higher-order stru role of anaplerosis in insulin secretion:and a section on the regu Huma ture of chromosomes.A discussion of how new biological roles of enzymes po endowin these RNAs with functional abilities such nlation.and succination reactions New information on theoperation of the eight citric cycle enzymes as a supercomplex or metabolon. ligand binding and even catalysis 20 Flectron transt Chanter 12 The strategies of re DNA nd Dis throughput technologies that allow global study of millions of tion on supercomplexes in electron transport. New insights into genes or prote s in a single experiment and a section devoted to he me anism of action of the FiF A ne ng mto SPR/ nd e dit o as well as cancer A ne Human riochemistry hox on car Chapter 13Th equations of tcs A new diolipin and its stabilization of respiratory supercomplexes,the 。at iogenesis of mitochondrial proteins,and the fission and fusion active enzyme and a catalytically inactive but not denatured state of the enzyme affords a deeper understanding of enzyme kinetics Chapter 21 Photosynthesis- -the most fundamental of all energy Ribozymes abzymes,and designer enzymes are featured here natur the biochemistry of photosy Chapter 14 Mechanisms of enzyme action.A new section on the inc ergy into ch it et role of quantum mechanical tunneling in ometry of synthases and the implications of this enzymes.New variability for the energetic cost of ATP formation.The recently Critical Develonments in Ric ape try box on accele tion he h rt ol on t enzyme reactions by electric fields Chapter 15 Enzym ter highlights allost om Co.ultimately leading ch formation regulation and o the two significant polysaccharides produced by plants. Chante nesis.gl ad tha na ion,a newly appreciate means to regulate meta phosphate nathway a De per Look feature on TIGAR.a he rel p53-induced enzyme that mimics fructose-2,6-bisphosphatase and binding proteins mvoglobin and hemoglobin. esponds to cellular stresses such as oncogenesi s and DNA dan on on o Chante A revised D NTPases and their role in molecular motors and a revised scc ntion of tion on the contraction cycle of skeletal muscle.New Human ATP promotes and supports the metabolism of cancer cells The Biochemistry box on the "tubulin code"post-translational modi interplay of phosphorylation and O-GleNAcylation in gluconeo- fications that coordinate the functions of microtubules enic gene transcription,particularly in the fasting state Chapter 17 An overview of metabolism,to prepare students for Chapter 23 Fatty acid oxidation.A new Deeper Look feature or the biochemistry of obesity describing the role of peroxisome omics,the study prolllerator-ac ctivated receptors in regulation of gene expression ir 巴9
xxxiv Preface Chapter 10 The structure and chemistry of nucleotides and nucleic acids. New appreciation of cyclic dinucleotides as signaling molecules, including the role of cGAMP in triggering a program of gene expression aimed at halting infection. An updated introduction to the many roles of small RNAs in the regulation of gene expression: miRNAs and the long, noncoding RNAs (lincRNAs). Chapter 11 The structure of nucleic acids and chromosomes. An overview of the next-generation DNA sequencing technologies, including emerging technologies to sequence single molecules of DNA. The techniques at the forefront of “personal genomics”: the ability to carry out low-cost sequencing of an individual’s genome and the implications of the information obtained on the diagnosis and treatment of disease. Also, creation of DNA molecules composed of not just two, but three, different base pairs opens up extraordinary potentials within synthetic biology. New structural models for chromatin at the level of its 30-nm fiber ‘secondary structure’ give insights into the long mysterious higher-order structure of chromosomes. A discussion of how new biological roles of RNA have come into sharper focus because of recent realizations that their three-dimensional architectures are conformationally dynamic, endowing these RNAs with functional abilities, such as ligand binding and even catalysis. Chapter 12 The strategies of recombinant DNA technology and gene cloning. New features include a section devoted to highthroughput technologies that allow global study of millions of genes or proteins in a single experiment and a section devoted to the emerging field of synthetic biology, with special emphasis on the use of CRISPR/Cas9 to edit genes and genomes. Chapter 13 The equations of enzyme kinetics. A new perspective on the response of enzyme reaction rate to increasing temperature is presented, wherein a temperature-dependent equilibrium between active enzyme and a catalytically inactive but not denatured state of the enzyme affords a deeper understanding of enzyme kinetics. Ribozymes, abzymes, and designer enzymes are featured here. Chapter 14 Mechanisms of enzyme action. A new section on the role of quantum mechanical tunneling in electron and proton transfer reactions of enzymes. New Human Biochemistry box on antibiotic resistance by (carbapenem-resistant) superbugs. New Critical Developments in Biochemistry box on acceleration of enzyme reactions by electric fields. Chapter 15 Enzyme regulation. This chapter highlights allosteric regulation and covalent modification of enzymes as important modes of metabolic regulation and includes discussion of reversible acetylation, a newly appreciated means to regulate metabolic enzymes. The relationship between quaternary structure and allosteric regulation is exemplified by a comparison of the oxygenbinding proteins myoglobin and hemoglobin. Chapter 16 Motor proteins. A revised discussion of P-loop NTPases and their role in molecular motors and a revised section on the contraction cycle of skeletal muscle. New Human Biochemistry box on the “tubulin code” post-translational modifications that coordinate the functions of microtubules. Chapter 17 An overview of metabolism, to prepare students for the ten chapters on metabolic pathways which follow. This edition highlights metabolomics, the study of all the metabolites in a cell at a particular moment, as the most accurate representation of what a cell is doing at any instant. Chapter 18 Glycolysis. A Critical Developments in Biochemistry feature that describes a modern interpretation of the Warburg effect in cancer. Expanded coverage of glucokinase and its role as a glucose sensor that recognizes glucose and initiates a signaling pathway that results in glucose-induced insulin secretion. New information on protein kinase M2 (PK M2), including its newlydiscovered protein kinase activity, its stimulation by SAICAR (an intermediate in the purine biosynthetic pathway), and its role in tumor proliferation. New coverage of the unregulated metabolism of dietary fructose in the liver, and its implications for insulin resistance, metabolic syndrome, and obesity. Chapter 19 The citric acid cycle. A new discussion of the structure of pyruvate dehydrogenase comple; a new Deeper Look feature on the role of anaplerosis in insulin secretion; and a section on the regulation of TCA cycle enzymes by acetylation. A new Human Biochemistry box on the roles of citric acid cycle metabolites in posttranslational modification of proteins, including acetylation, succinylation, and succination reactions. New information on the operation of the eight citric cycle enzymes as a supercomplex or metabolon. Chapter 20 Electron transport and oxidative phosphorylation. Discussion of the new structure of Complex I and new information on supercomplexes in electron transport. New insights into the mechanism of action of the F1F0-ATP synthase. A new Human Biochemistry box describing mitochondrial dynamics and its role in cardiovascular, neurodegenerative, and endocrine diseases, as well as cancer. A new Human Biochemistry box on cardiolipin and its stabilization of respiratory supercomplexes, the biogenesis of mitochondrial proteins, and the fission and fusion processes of mitochondria. Chapter 21 Photosynthesis—the most fundamental of all energy transduction systems in nature: the biochemistry of photosynthesis; the transformation of light energy into chemical energy. New information on species variability in the c-subunit stoichiometry of CF1CF0-ATP synthases and the implications of this variability for the energetic cost of ATP formation. The recently described structure of the Mn4CaO5 oxygen-evolving cluster at the heart of Photosystem II is presented. Emphasis on the pathway of carbon dioxide fixation that synthesizes organic molecules from CO2, ultimately leading to cellulose and starch formation, the two significant polysaccharides produced by plants. Chapter 22 Gluconeogenesis, glycogen metabolism, and the pentose phosphate pathway. A Deeper Look feature on TIGAR, a p53-induced enzyme that mimics fructose-2,6-bisphosphatase and responds to cellular stresses such as oncogenesis and DNA damage events; new information on O-GlcNAc signaling and the hexosamine biosynthetic pathway; and a new Critical Developments in Biochemistry feature describing how consumption of ATP promotes and supports the metabolism of cancer cells. The interplay of phosphorylation and O-GlcNAcylation in gluconeogenic gene transcription, particularly in the fasting state. Chapter 23 Fatty acid oxidation. A new Deeper Look feature on the biochemistry of obesity describing the role of peroxisome proliferator-activated receptors in regulation of gene expression in Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
Preface Chapter 28 DNA metabolism.The multiplicity of dNa poly merases.A new section to integrate DNA replication,recom of the Boxidation pathway and migration of its fatty acyl sub interdependent aspects of DNA strates gnegatively-cha nnel without diffu othe new feature is of 6 sion.lipid metabo lism.metabolic rate.and resistance to oxidative stress immunology Chapter 24 Lipid biosynthesis.A Human Biochemistry box fea turing the role of NPCI and NPC2 proteins in cholesterol trans. nta oI post APOC3an apolipoprotein that regulates plasma triglyceride Mediator and its role as a bridge between enhancers of tran levels;and new cholesterol-lowering drugs that target PCSK9.an scription and RNA polymerase II.The competing conceptso LDL receptor chaperone. histone code and histone crosstalk are discussed. he Chapter 25 The assimilation of inorganic nitrogen into organic nitro gen metabolites and biosynthesis of the amino acids Di 0n0 Chapter 30 Protein synthesis.The genetic code.Aminoacyl-tRNA t a and the scond ther,tryptophan catabolism by the kynurenine pathway is p tions with the ribosome new structures for the ribosome RF-2 because this pathway has been implicated in human neurodegenera- termination complex,and the more richly detailed appreciation of tive disorders such as Parkinson's and Alzheimer's disease the events in eukaryotic translation initiation highlight this chap Chapter 26 Biosynthesis of purines and pyrimidines Tetrahydrofo ntheCboIbgameTethcredibosomesandnes ate and I-carbon metabolism.Purinosomes as multi-enzyme assem Chapter 31 Completing the protein life cycl Modes of post ells The Pro tain folding and n its revelations regarding regulation by nucleotides are presented. es A new Human Biochemistry box on chaperones that func Chapter 27 Sum s by which cells recycle their sensor and the newly appreciated protection of AMPK by ADP are discu ssed.mTORCI as the integ ator Chapter 32 Cell signaling and neurotransmission.Intracellular the ent intake.AMPK.SIRTI and protein acetylation and the ce A Human riochemistry feature on neurexins and neuroligins quences that these relationships have for calorie intake control and which function as scaffolding proteins in the formation of syn apses and the regulation of synaptic transmission.learning.and memory. Supporting Materials For the instructor Please visit http/wwy com/hemistry/garre/more informatior For the Student Please visit http://www.cengage.com/chemistry/garrett/biocheme for more information about student resources for this text Acknowledgments on how to construct an effective textbook
Preface xxxv fatty acid oxidation and triglyceride metabolism. A new A Deeper Look box describing the trifunctional enzyme complex at the heart of the β-oxidation pathway and migration of its fatty acyl substrates along a negatively-charged substrate channel without diffusing into the bulk solvent. The role of β-hydroxybutyrate as a signaling metabolite that regulates gene expression, lipid metabolism, metabolic rate, and resistance to oxidative stress. Chapter 24 Lipid biosynthesis. A Human Biochemistry box featuring the role of NPC1 and NPC2 proteins in cholesterol transport in lysosomes and Niemann-Pick type C disease. Four new Human Biochemistry boxes: Lipins—phosphatases essential for triglyceride synthesis and other functions; Lipoxins—antiinflammatory eicosanoid products of transcellular metabolism; APOC3—an apolipoprotein that regulates plasma triglyceride levels; and new cholesterol-lowering drugs that target PCSK9, an LDL receptor chaperone. Chapter 25 The assimilation of inorganic nitrogen into organic nitrogen metabolites and biosynthesis of the amino acids. Discussion of glutamine and its metabolic significance as the most abundant amino acid in human body fluids and tissues; glutamine and cancer. Further, tryptophan catabolism by the kynurenine pathway is presented, because this pathway has been implicated in human neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Chapter 26 Biosynthesis of purines and pyrimidines. Tetrahydrofolate and 1-carbon metabolism. Purinosomes as multi-enzyme assemblages of the purine biosynthetic enzymes. The purine pathway intermediate SAICAR as a key signal in reprogramming metabolism in cancer cells. The structure of human ribonucleotide reductase with its revelations regarding regulation by nucleotides are presented. Chapter 27 Summing up metabolism and the metabolic roles of the various organs. AMP-kinase (AMPK) as the cell’s energy charge sensor and the newly appreciated protection of AMPK by ADP are discussed. mTORC1 as the integrator of information about nutrient status and as the regulator of cellular synthesis is introduced. The regulation of eating behavior. The relationships between nutrient intake, AMPK, SIRT1 and protein acetylation and the consequences that these relationships have for caloric intake control and the development of metabolic syndrome. These interactions illuminate the underlying causes of the current obesity epidemic. Chapter 28 DNA metabolism. The multiplicity of DNA polymerases. A new section to integrate DNA replication, recombination, and repair as interdependent aspects of DNA metabolism introduces this chapter. Another new feature is an illustration of how homologous recombination helps to prevent cancer. Genetic recombination, protein diversity, and immunology. Chapter 29 Transcription; DNA-dependent RNA polymerases. Transcription regulation in bacteria and in eukaryotes, An update of eukaryotic translation initiation events in eukaryotes and the emerging science of miRNAs and lncRNAs as key regulators of post-transcriptional gene expression are presented, along with new structural and functional information about Mediator and its role as a bridge between enhancers of transcription and RNA polymerase II. The competing concepts of the histone code and histone crosstalk are discussed. The spliceosome. Chapter 30 Protein synthesis. The genetic code. Aminoacyl-tRNA synthetases and the second genetic code. New features of the G-protein family members, Ef-Tu and EF-G, and their interactions with the ribosome, new structures for the ribosome RF-2 termination complex, and the more richly detailed appreciation of the events in eukaryotic translation initiation highlight this chapter. The ribosome as a ribozyme. Tethered ribosomes and new frontiers in synthetic biology. Chapter 31 Completing the protein life cycle. Modes of posttranscriptional modification that control the functional protein pool, Protein folding and neurodegenerative protein folding diseases. A new Human Biochemistry box on chaperones that function by stress-induced protein unfolding. A Human Biochemistry highlight on autophagy, the process by which cells recycle their materials. Expanded coverage of Htr proteins. Chapter 32 Cell signaling and neurotransmission. Intracellular responses to extracellular signals. Protein kinase cascades. Organization and integration of signaling pathways. Sensory systems. A Human Biochemistry feature on neurexins and neuroligins, which function as scaffolding proteins in the formation of synapses and the regulation of synaptic transmission, learning, and memory. Supporting Materials For the Instructor Please visit http://www.cengage.com/chemistry/garrett/biochem6e for more information about instructor resources for this text. For the Student Please visit http://www.cengage.com/chemistry/garrett/biochem6e for more information about student resources for this text. Acknowledgments We are indebted to the many experts in biochemistry and molecular biology who carefully reviewed this book at several stages for their outstanding and invaluable advice on how to construct an effective textbook. Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
Preface Weiguo Coa,Clemson University Christine Smith.University of New Mexico Anya Goodman.California Polvtechnic Cheryl Ingram-Smith,Clemson Universit Larry Yet,University of South Alabama Hiroshi Nakai,Georgetown University Gregory Marks.Carroll College Sandra Bares,Alcorn State University Stephen Campion.Alvernia College Wealso wish to gratefully acknowledge many other people who assisted and encouraged us ns a legacy of publi grateful for it.Maur Ros our new Senior Product Manag ha ea asm and an unwavering emphasis on student learning as the fundamental purpose of our collective enterprise.Sandi Kiselica,Senior Developmental Editor,shepherded the firs editions of th his th thand.the nd lim scale in a textbook's dimen sions She is truly a colleague in these Welso appaud the unsung but absolutely indispensable contributions by those whose efforts trar final pro ) it is due to them.The beautiful illustrations that not thi testament to the of MPS Limited and to the legacy of John Woolsey and Patrick Lane at J/B Woolsey Associates Manojkirin Chan tion of the k. mine and lats e the artistic contributions of Michal Sabat,Senior Scientistin Ds总Oee8eae义oM L-based molecular graphics in B.S.(c nistn rad odels library.a multi-faceted task requiring scientific knowledge and a of the We owe a spe ank you to ary Jur erant friend David,Emily.and Andrew Grisham.Also to be ap ciated is laspe Hungaran Puli whose uns cing eyes viewed life with an energetic curiosity we ncy.a Gold t epic patience d pe's re in ther pursuits and our refections on life We hone this sixth edition of our texthook has aptured the growing sense of wonder and imagination that researchers,teachers,and stu- dents share as they explore the ever-changing world of biochemistry. 'Imagination is more im tant than knowledge for while knowledge defines all we -Albert einstein Reginald H.Garrett Charles M.Grisham Jax and Jaspe November.2015
xxxvi Preface Weiguo Coa, Clemson University Christine Smith, University of New Mexico Anya Goodman, California Polytechnic Cheryl Ingram-Smith, Clemson University Larry Yet, University of South Alabama Hiroshi Nakai, Georgetown University Gregory Marks, Carroll College Sandra Barnes, Alcorn State University Stephen Campion, Alvernia College We also wish to gratefully acknowledge many other people who assisted and encouraged us in this endeavor. This book remains a legacy of publisher John Vondeling, who originally recruited us to its authorship. We sense his presence still nurturing our book and we are grateful for it. Maureen Rosener, our new Senior Product Manager, has brought enthusiasm and an unwavering emphasis on student learning as the fundamental purpose of our collective enterprise. Sandi Kiselica, Senior Developmental Editor, shepherded the first four editions of this text through conception to production. Any success this edition has will become part of her legacy. Elizabeth Woods, the Content Developer for this edition, has kept us focused on the matters at hand, the urgencies of the schedule, and limits of scale in a textbook’s dimensions. She is truly a colleague in these endeavors. We also applaud the unsung but absolutely indispensable contributions by those whose efforts transformed a rough manuscript into this final product: Teresa Trego, Senior Content Project Manager; Edward Dionne, Project Manager at MPS Limited. If this book has visual appeal and editorial grace, it is due to them. The beautiful illustrations that not only decorate this text but also explain its contents are a testament to the creative work of MPS Limited and to the legacy of John Woolsey and Patrick Lane at J/B Woolsey Associates. Manojkirin Chander at Lumina Datamatics Limited assisted in the selection of the wonderful photographs. We are thankful to our many colleagues who provided original art and graphic images for this work, particularly Professor Jane Richardson of Duke University. We are eager to acknowledge the scientific and artistic contributions of Michal Sabat, Senior Scientist in the Department of Materials Science and Engineering at the University of Virginia. Michal was the creator of most of the PyMOL-based molecular graphics in this book. Much of the visual appeal that you will find in these pages gives testimony to his fine craftsmanship and his unflagging dedication to our purpose. Elizabeth Magnotti, recent B.S. (chemistry) graduate of the University of Virginia, coordinated the student development of the ActiveModels library, a multi-faceted task requiring scientific knowledge and a sense of the important. We owe a special thank you to Rosemary Jurbala Grisham, much loved spouse of Charles and wonderfully tolerant friend of Reg. Also to be acknowledged with love and pride are Georgia Cobb Garrett, spouse of Reg, and our children, Jeffrey, Randal, and Robert Garrett, and David, Emily, and Andrew Grisham. Also to be appreciated is Jasper, the Hungarian Puli whose unseeing eyes viewed life with an energetic curiosity we all should emulate. Memories of Clancy, a Golden Retriever of epic patience and perspicuity; Jazmine, the alpha dog of the Puli troika; and Jatszi and Jax, attendant to Charlie’s deepest thoughts and daily activities, were a constant presence to our days as authors, our joys in other pursuits, and our reflections on life. We hope this sixth edition of our textbook has captured the growing sense of wonder and imagination that researchers, teachers, and students share as they explore the ever-changing world of biochemistry. “Imagination is more important than knowledge. For while knowledge defines all we currently know and understand, imagination points to all we might yet discover and create.” —Albert Einstein Reginald H. Garrett Charles M. Grisham Charlottesville, VA Ivy, VA November, 2015 Jazmine and Jatszi Clancy Jax and Jasper Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
The Facts of Life: PART I MoLecular Chemistry Is the Logic COMPONENTS OF CELLS of Biological Phenomena iea6cwaowhaia Sperm fertilizing an egg ESSENTIAL QUESTION KEY QUESTIONS molecule 13 15 moscreplicate themselves with exceptional fidelity.The compestruc 1.6 What Are Viruses? mistry of organic reactions.Indeed.cellular constituents.orbioes th spectacular diversity of life.the intricaey of biological structuresand theco of vital mechanisms,life functions are ultimately interpretable in chemical terms. Chemistry is the logic of biological phenomena.Living organisms are self-sustaining sys- ems of chemical reactions. 1.1 What Are the Distinctive Properties of Living Systems? n eecu
Molecules are lifeless. Yet, in appropriate complexity and number, molecules compose living things. These living systems are distinct from the inanimate world because they have certain extraordinary properties. They can grow, move, perform the incredible chemistry of metabolism, respond to stimuli from the environment, and, most significantly, replicate themselves with exceptional fidelity. The complex structure and behavior of living organisms veil the basic truth that their molecular constitution can be described and understood. The chemistry of the living cell resembles the chemistry of organic reactions. Indeed, cellular constituents, or biomolecules, must conform to the chemical and physical principles that govern all matter. Despite the spectacular diversity of life, the intricacy of biological structures, and the complexity of vital mechanisms, life functions are ultimately interpretable in chemical terms. Chemistry is the logic of biological phenomena. Living organisms are self-sustaining systems of chemical reactions. 1.1 What Are the Distinctive Properties of Living Systems? First, the most obvious quality of living organisms is that they are complicated and highly organized (Figure 1.1). For example, organisms large enough to be seen with the naked eye are composed of many cells, typically of many types. In turn, these cells possess subcellular structures, called organelles, which are complex assemblies of very large The Facts of Life: 1 Chemistry Is the Logic of Biological Phenomena KEY QUESTIONS 1.1 What Are the Distinctive Properties of Living Systems? 1.2 What Kinds of Molecules Are Biomolecules? 1.3 What Is the Structural Organization of Complex Biomolecules? 1.4 How Do the Properties of Biomolecules Reflect Their Fitness to the Living Condition? 1.5 What Are the Organization and Structure of Cells? 1.6 What Are Viruses? “…everything that living things do can be understood in terms of the jigglings and wigglings of atoms.” Richard P. Feynman. Lectures on Physics, Addison-Wesley, 1963 Essential Question Molecules are lifeless. Yet, the properties of living things derive from the properties of molecules. Despite the spectacular diversity of life, the elaborate structure of biological molecules, and the complexity of vital mechanisms, are life functions ultimately interpretable in chemical terms? Part I Molecular Components of cells Marmaduke St. John/Alamy Sperm fertilizing an egg. Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it