Contentsin BriefContentsThe Foundations of BiochemistryPrefacevili1TheFoundations of Biochemistry21.1 Cellular FoundationsCells Are the Structural and Functional41STRUCTUREAND CATALYSIS3UnitsofAllLivingOrganisms432Water3Cellular Dimensions Are Lirnited by Diffusion4713There Are Three Distinct Domains of LifeAmocdsPtidndro5Escherichiacoli Isthe Most-StudiedBacterium1134 TheThree-Dimensional Structure of ProteinsEukaryotic Cells Havea Variety of Membranous5Protein Function1537Organelles,Which Can Be IsolatedforStudy6183EnzymesTheCytoplasm Is Organizedby theCytoskeleton8235and Is Highly Dynamic7Carbohydrates andGlycobiology9Cells Build Supranolecular Structures2718NucleotidesandNucleicAcidsInVitro StudiesMayOverlook Important9 DNA-Based Information Technologies30310Interactionsamong Molecules34310Lipids37111 Biological Membranesand Transport111.2Chemical Foundations41712 BiosignalingBiomoleculesAreCompoundsof Carbonwith11a Variety of Functional Groups485II BIOENERGETICSANDMETABOLISM13Cells Contain a Universal Set of Small Molecules13Bioenergetics and BiochemicalReactionTypes489Box1-1MolecularWeight,MolecularMass,and14Their Correct Units14GlyolyiGluconogensisandthePenMacromolecules Are the Major527Phosphate Pathway14Constituents of Cells15Principlesof MetabolicRegulation569Three-Dimensional Structure Is Described61516The CitricAcid Cycle15byConfiguration and Conformation1717FattyAcid Catabolism647Box1-2LouisPasteurand OpticalActivity:InVino,VeritasInteractionsbetweenBiomolecules18 AminoAcid OxidationandtheProduction of Urea67318AreStereospecific70719 OxidativePhosphorylation and Photophosphorylation77320 CarbohydrateBiosynthesis in Piants and Bacteria191.3 Physical Foundations80521 Lipid BiosynthesisLiving Organisms Exist in a Dynamic22BiosynthesisofAminoAcids,Nucleotides,anSteadyState,NeveratEquilibriumwith20851Related MolectulesTheir SurroundingsOrganisms Transform Energy and Matter23 Hormonal Requlation and Integration of20frorn Their Surroundings901Mammalian Metabolism21Box 1-3Entropy:The Advantages of Being DisorganizedTheFlow of Electrons Provides Energy945IIIINFORMATIONPATHWAYS22forOrganisms94724GenesandChromosomesCreating and Maintaining Order Requires Work9752225DNAMetabolismandEnergy22Energy Coupling Links Reactions in Biology26RNAMetabolism1021Keq and AG' Are Measures of a Reaction's106527ProteinMetabolism24Tendency toProceed Spontaneously111528 RequlationofGeneExpression25EnzymesPromoteSequencesof ChemicalReactionsMetabolism Is Regulated toAchieve BalanceAppendixACommonAbbreviationsintheBiochemical26andEconomyResearchLiteratureA-1AppendixBAbbreviated SolutionstoProblems AS-1271.4GeneticFoundationsGlossaryG-1Genetic Continuity Is Vested in Single27Credits C-1DNA MoleculesThe Structure of DNAAllowsforIts ReplicationIndex I-128and Repair with Near-Perfect FidelityThe Linear Sequence in DNA Encodes Proteins with29Three-DimensionalStructuresxV
Preface 1 The Foundations of Biochemistry I STRUCTURE AND CATAIYSIS 2 Water 3 Amino Acids. Peptides, and Proteins 4 The Three-Dimensional Strufiure of Proteins 5 Protein Funrtion 6 Enzymes 7 Carbohydrates and Glyrobiology 8 Nucleotides and Nucleic Aids 9 DNA-Based Information Technoloqies 10 Lipids 11 Biological Membranes and Transport 12 Biosignaling II BIOENERGETICS AND METABOLISM 1 3 Bioenergetics and Biochemical Reaction Types 1 4 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway '15 Principles of Metabolic Regulation 16 The Citric Arid tyde 17 Fatty Acid (atabolism 18 Amino Acid 0xidation and the Production of Urea 1 9 Oxidative Phosphorylation and Photophosphorylation 20 ftrbohydrate Biosynthesis in Plants and Bacteria 2l Lipid Biosynthesis 22 Biosynthesis of Amino Acids, Nucleotides, and Related Mohcules 23 Hormonal Regulation andlntegration of Mammalian Metabolism III INFORMATION PATHWAYS 24 Genes and Chromosomes 25 DNA Metabolism 26 RNA Metabolism 27 Protein Mrtabolism 28 Regulation ofGene Expression 1 The Foundations of Biochemistry 1.1 (ellular Foundations Cells Are the Structural and Functional Units of All Living Organisms Cellular Dimensions Are Limited by Diffusion There Are Three Distinct Domains of Life E sch,erichia coli ls the Most-Studied Bacterium Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study The Cytoplasm Is Organized by the Cytoskeleton and Is HigNy Dynamic Cells Build Supramolecular Structures In Vitro Studies May Overlook Important Interactions among Molecules 1.2 (hemicalFoundations l1 Biomolecules Are Compounds of Carbon with a Variety of Functional Groups 11 Cells Contain a Universal Set of Small Molecules 13 Box 1-l MolecularWeight Molecular Mass,and Their Conect Units Macromolecules Are the Major Constituents of Cells Three-Dimensional Structure Is Described by Configuration and Conformation Box 1-2 louis Pasteurand 0ptical ActiuatyilnVino,Vefitus lnteractions between Biomolecules Are Stereospeciic vilt a 41 +.1 71 113 153 183 235 271 103 343 371 417 485 489 527 569 515 olt 673 v07 773 805 851 90i 945 947 975 1021 1065 't1 15 14 t4 15 1 7 18 J J 4 5 .7 8 I 10 Appendix A Common Abbreviations in the Biochemical Re sea rch Literatu re A- 1 Appendix B Abbreviated Solutions to Problems AS-l GlossaryG-| CreditsC-l lndexl-l 1.3 PhpicalFoundations 19 Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings 20 Organisms Ttansform Energr and Matter from Their Surroundings 20 Boxl-3Entropy:TheAdvantagesofBeingDisotganized 21 The Flow of Electrons Provides Energ5r for Organisms 22 Creating and Maintaining Order Requires Work andEnerry 22 Energ5l Coupling Links Reactions in Biologr 22 K"rand AG" Are Measures of a Reaction's Tendencyto ProceedSpontaneously 24 Enzymes Promote Sequences of Chemical Reactions 25 Metabolism Is Regr:lated to Achieve Balance andEconomy 26 1.4 Genetic Foundations 27 Genetic Continuity Is Vested in Single DNA Molecnles 27 The Structure of DNA Allows for Its Replication and Repair with Near-Perfect Fidelity 28 The Linear Sequence in DNA Encodes Proteins with Ttree-Dimensional Structures 29 xv
xviContents291.5 EvolutionaryFoundations652.4 Water as a ReactantChanges in the Hereditary Instructions2.5 The Fitness of the Aqueous Environment29AllowEvolution65for Living Organisms30Biomolecules First Arose by Chemical EvolutionRNA or Related Precursors May Have Been the31First Genes and CatalystsBiological Evolution Began More Than713AminoAcids,Peptides,andProtein32Three and a Half Billion Years Ago32The First Cell Probably Used Inorganic Fuels723.1AminoAcidsEukaryotic Cells Evolved from Simpler72Amino Acids Share Common Structural Features33Precursors in Several StagesThe Amino Acid Residues in Proteins AreMolecular Anatorny Reveals Evolutionary74LStereoisomers33Relationships74ArninoAcids CanBeClassifiedbyRGroupFunctional Genomics Shows the Allocations ofBox3-1Methods:Absorption of Light byMolecules:35Genes toSpecific Cellular Processes76TheLambert-BeerLawGenomic Comparisons Have Increasing35UncommonAminoAcidsAlsoHaveImportancein HumanBiologyand Medicine77ImportantFunctions78Amino Acids Can Act as Acids and Bases41-STRUCTUREAND CATALYSIS79Amino Acids Have Characteristic Titration CurvesTitration Curves Predict the Electric2Water4380Charge of Armino AcidsAmino Acids Differ in Their Acid-Base Properties812.1Weak Interactions in Aqueous Systems43Hydrogen Bonding Gives Water ItsUnusual Properties43823.2 Peptides and ProteinsWater Forms Hydrogen Bonds with Polar Solutes45Peptides Are Chains of Amino Acids82Water Interacts Electrostatically withPeptides Can Be DistinguishedbyTheir46Charged Solutes82onization BehaviorEntropy Increases as CrystallineBiologically Active Peptides and PolypeptidesSubstances Dissolve47Occur ina Vast Range of Sizes andNonpolar Gases Are Poorly Soluble in Water4783CompositionsNonpolarCompounds Force EnergeticallySome Proteins Contain Chemical GroupsUnfavorable Changes in the Structure of Water4784OtherThan Amino Acidsvan der Waals Interactions Are Weak InteratomicAttractions49Weak Interactions Are Crucial to Macromolecular853.3 Working with ProteinsStructure and Function50Proteins Can Be Separated and Purified85Solutes Affect the Colligative Properties ofProteins Can Be Separated and Characterized byAqueous Solutions5188Electrophoresis91UnseparatedProteins CanBeQuantified2.2lonizationofWater,Weak Acids,andWeakBases54Pure Water Is Slightly Ionized543.4 The Structure of Proteins:Primary Structure92The lonization of Water Is Expressed by anEquilibrium Constant55TheFunction of a Protein Depends on ItsThepH ScaleDesignates theH+and OH93Arnino Acid SequenceConcentrations56The Amino Acid Sequences of Millions ofWeak Acids and Bases Have Characteristic93Proteins Have Been DeterminedAcidDissociation Constants57Short Polypeptides Are Sequenced withTitration Curves Reveal the pKa of Weak Acids5894AutomatedProceduresLarge Proteins Must Be Sequenced in Smaller2.3 Buffering against pH Changes in95SegmentsBiological Systems59AminoAcid Sequences Can Also BeDeducedby98Buffers Are Mixtures of Weak Acids and TheirOtherMethodsConjugate Bases59Box3-2 Methods:Investigating Proteins withThe Henderson-Hasselbalch Equation Relates98Mass SpectrometrypH,pKa,andBufferConcentration60Small Peptides and Proteins Can Be ChemicallyWeak Acids or Bases Buffer Cells andSynthesized10061TissuesagainstpHChangesAminoAcid SequencesProvideImportantUntreated Diabetes Produces102Biochemical InformationLife-Threatening Acidosis63Protein Sequences Can Elucidate the History ofBox 2-1Medicine:On Being One's Own RabbitLife on Earth102(Don't Try This at Homel)64103Box3-3 Consensus Sequences and Sequence Logos
1.5 Evolutionary Foundations Changes in the Hereditary Instructions Allow Evolution Biomolecu-les First Arose by Chemical Evolution RNA or Related Precursors May Have Been the First Genes and Catalysts Biological Evolution Began More Than Three and a Half Billion Years Ago The First Cell Probably Used Inorganic Fuels Eukaryotic Cells Evolved from Simpler Precursors in Several Stages Molecular Anatomy Reveals Evolutionary Relationships Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes Genomic Comparisons Have Increasir4; Importance in Human Biology and Medicine I STRUCTURE AND CATALYSIS 2 Water 2.1 Weak Interactions in Aqueous Systems Hydrogen Bonding Gives Water lts Unusual Properties Water Forms Hydrogen Bonds with Polar Solutes Water Interacts Electrostatically with Charged Solutes Entropy Increases as Crystalline Substances Dissolve Nonpolar Gases Are Poorly Soluble in Water Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water van der Waals Interactions Are Weak Interatomic Attractions Weak Interactions Are Crucial to Macromolecular Structure and Function Solutes Affect the Colligative Properties of Aqueous Solutions 2.2 lonization ofWater, Weak Acids, and Weak Bases Pure Water Is Slightly Ionized The Ionization of Water Is Expressed by an Equilibrium Constant The pH Scale Designates the H+ and OHConcentrations Weak Acids and Bases Have Characteristic Acid Dissociation Constants Titration Curves Reveal the pK. of Weak Acids 2.3 Buffering aainst pH Changes in Biological Systems Buffers Are Mixtures of Weak Acids and Their Conjugate Bases The Henderson-Hasselbalch Equation Relates pH, pK., and Buffer Concentration Weak Acids or Bases Buffer Cells and Tissues against pH Changes Untreated Diabetes Produces Life-Threatening Acidosis Box 2-1 Medicine:0n Being 0net Own Rabbit (Don't Try This at Home!) 2.4 Water as a Reactant 2.5 The Fitness ofthe Aqueous Environment for Living 0rganisms 3 Amino Acids, Peptides, and Proteins 3.1 Amino Acids Amino Acids Share Common Structural Features The Amino Acid Residues in Proteins Are L Stereoisomers Amino Acids Can Be Classified by R Group Box 3-1 Methods: Absorption of Lig ht by Molecules: Ihe lambert-Beel Law Uncommon Amino Acids Also Have Irnportant Functions Amino Acids Can Act as Acids and Bases Amino Acids Have Characteristic Titration Curves Titration Curves Predict the Electric Charge of Amino Acids Amino Acids Differ in Their Acid-Base Properties 3.2 Peptides and Proteins Peptides Are Chains of Amino Acids Peptides Can Be Distinguished by Their Ionization Behavior Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes and Compositions Some Proteins Contain Chemical Groups Other Than Amino Acids 3.3 Working with Proteins Proteins Can Be Separated and Purified Proteins Can Be Separated and Characterized by Electrophoresis Unseparated Proteins Can Be Quantified 65 65 7'.| 29 tq 30 31 32 32 33 35 35 72 72 ,74 74 41 43 76 77 78 70 80 81 82 82 82 83 84 85 85 88 91 43 43 45 47 47 49 50 51 54 54 O I 58 3.4 The Structure of Proteins: Primary Structure 92 The Function of a Protein Depends on Its Amino Acid Sequence 93 The Amino Acid Sequences of Millions of Proteins Have Been Determined 93 Short Polypeptides Are Sequenced with Automated Procedures 94 Large Proteins Must Be Sequenced in Smaller Segments 95 Amino Acid Sequences Can Also Be Deduced by Other Methods 98 Box3-2 Methods; Investigating Proteins with Mass Spectrometry 98 Small Peptides and Proteins Can Be Chemically Synthesized 100 Amino Acid Sequences Provide Important Biochemical Information I02 Protein Sequences Can Elucidate the History of Life on Earth 102 Box3-3 Consensus Sequencesand Sequence logos 103 59 61 64
xviiContents158The Three-Dimensional Structure of Proteins 113Protein Structure Affects How Ligands Bind158HemoglobinTransports Oxygen in BloodHemoglobin Subunits Are StructurallySimilarto4.1Overviewof ProteinStructure113159MyoglobinA Protein's Conformation Is Stabilized Largely byHemoglobin Undergoes a Structural Change onWeak Interactions114160Binding OxygenThe Peptide Bond Is Rigid and Planar115160HemoglobinBinds Oxygen Cooperatively4.2Protein Secondary Structure117CooperativeLigand Binding Can BeDescribedQuantitatively162The α Helix Is a Common Protein Secondary163Box5-1Medicine:Carbon Monoxide:A StealthyKillerStructure117Two Models Suggest Mechanisms forBox 4-1Methods:Knowing the Right Hand from theLef118165Cooperative BindingAmino Acid SequenceAffects Stability of the165Hemoglobin Also Transports H+and COαHelix119OxygenBinding toHemoglobin IsRegulatedbyTheβConformationOrganizes Polypeptide1672,3-BisphosphoglycerateChains into Sheets120Sickle-Cell Anemia Is a Molecular Diseaseβ Turns Are Common in Proteins121168of HemoglobinCommon Secondary Structures HaveCharacteristic Dihedral Angles1215.2 Complementary Interactions betweenCommonSecondaryStructures Can BeProteins and Ligands:The Immune122Assessed by CircularDichroism170SystemandImmunoglobulins4.3 ProteinTertiary and QuaternaryStructures123The Irnrnune Response Features a Specialized170Fibrous Proteins Are Adapted for aArray of Cells and ProteinsAntibodies Have Two Identical Antigen-Binding Sites 171Structural Function123173Antibodies Bind Tightly and Specifically to AntigenBox 4-2 Permanent Waving Is Biochemical Engineering125The Antibody-Antigen Interaction Is the Basis for aBox43Medicine:WhySailors,Explorers,and College173Variety of Important Analytical ProceduresStudents Should Eat Their Fresh Fruits and Vegetables1265.3Protein Interactions Modulated byChemical Energy:Box4-4The Protein Data Bank129175Actin,Myosin,andMolecularMotorStructural Diversity Reffects Functional DiversityThe Major Proteins of Muscle Are Myosin and Actin175inGlobularProteins129Myoglobin Provided Early Clues about theComplexityAdditional Proteins Organize theThin andThickof GlobularProtein Structure176129Filaments into Ordered StructuresGlobular Proteins Have a Variety ofMyosin Thick Filaments Slide along178Tertiary Structures131ActinThinFilamentsBox4-5Methods:Methods forDetermining theThree-Dimensional Structure ofa Protein132Protein Motifs Are the Basis for Protein1836Enzymes136Structural ClassificationProteinQuaternary Structures Rangefrom Simple1836.1An Introductionto EnzymesDimers to Large Complexes138Most Enzymes Are Proteins184Enzymes Are Classified by theReactions4.4 Protein Denaturation and Folding140184They CatalyzeLoss of Protein Structure Results inLoss of Function1401866.2HowEnzymesWorkAminoAcid Sequence Determines186EnzymesAffectReactionRates,NotEquilibriaTertiary Structure141Reaction Rates and Equilibria Have PrecisePolypeptides Fold Rapidlyby a StepwiseProcess142188Thermodynamic DefinitionsSomeProteins Undergo Assisted Folding143AFewPrinciples ExplaintheCatalyticPowerandDefects in Protein Folding May Be the Molecular188Specificity of EnzymesBasis for a Wide Range of Human GeneticWeak Interactions between EnzyineandDisorders145SubstrateAreOptimizedintheTransitionState189Box 46Medicine: Death by Misfolding:The Prion Diseases147Binding Energy Contributes to Reaction191Specificity and Catalysis192SpecificCatalyticGroupsContributetoCatalysis153Protein Function6.3EnzymeKinetics as an Approachto Understanding5.1Reversible Bindingofa Protein toa Ligands194Mechanism154Oxygen-Binding ProteinsSubstrateConcentrationAffectstheRateof154194Oxygen Can Bind toa HemeProsthetic GroupEnzyme-Catalyzed ReactionsMyoglobin Has a SingleBinding Sitefor Oxygen155The Relationship between Substrate ConcentrationProtein-Ligand Interactions Can Be Describedand Reaction Rate Can BeExpressed155195QuantitativelyQuantitatively
4 The Three-Dimensional Strueture ofProteins 'll3 Protein Structure Affects How Ligands Bind Hemoglobin Tfansports Oxygen in Blood Hemoglobin Subunits Are Structurally Similar to Myoglobin Hemo$obin Undergoes a Structural Change on Binding Oxygen Hemoglobin Binds Oxygen Cooperatively Cooperative Ligand Binding Can Be Described Quantitatively Box 5-1 Medicine:Cahon Moxide:A Stealthy Killer 5.2 (omplementary lnteradions between Proteins and Ligands:The lmmune System and lmmunoglobulins 6 Enzymes Contents xvii 160 160 162 163 158 158 159 4.1 0verview of Protein Structure A Protein's Con-formation Is Stabilized Largely by Weak Interactions The Peptide Bond Is Rigid and Planar 4.2 Protein 5econdary Structure The a Helix Is a Common Protein Secondary Structure Box 4-1 Methods:Knowing the Right Hand from the left Amino Acid Sequence Affects Stability of the a Helix The B Conformation Organizes Polypeptide Chains into Sheets B Tirrns Are Common in Proteins Common Secondary Structures Have Characteristic Dihedral Angles Common Secondary Structures Can Be Assessed by Circular Dichroism 4.3 Protein Tertiary and Quaternary Structures Fibrous Proteins Are Adapted for a Structural Function Box 4-2 Permanent Waving lsBiochemical Engineering Box4-3 Medicine:Why Sailors, Explorers, and College Students Should Eat Their Fresh Fruits and Vegetables Box 4-4 The Protein Data Bank Structural Diversity Reflects Functional Diversity in Globular Proteins Myoglobin Provided Early Clues about the Complexity of Globr-rlar Protein Structure Globular Proteins Have a Variety of Tertiary Structures Box4-5 Methods; Methods for Determining the Three-Dimensi0nal Stlucture of a Protein Protein Motifs Are the Basis for Protein Structural Classiflcation Protein Quaternary Structures Range from Simple Dimers to Large Complexes 4.4 Protein Denaturation and Folding Loss of Protein Structure Results in Loss of Function Amino Acid Sequence Determines Tertiary Structure Polypeptides Fold Rapidly by a Stepwise Process Some Proteins Undergo Assisted Folding Defects in Protein Folding May Be the Molecular Basis for a Wide Range of Human Genetic Disorders Box4-6 Medicine: Death by Misfolding:The Prion Diseases 5 Protein Funetion TWo Models Suggest Mechanisms for Cooperative Binding 165 Hemoglobin Also Tfansports H+ and CO2 165 Oxygen Binding to Hemoglobin Is Regulated by 2,3-Bisphospho$ycerate 167 Sickle-Cell Anemia Is a Molecular Disease of Hemo$obin 168 113 rt4 115 117 \t7 118 119 r20 1.21. r2r r22 123 \23 125 174 5,1 Reversible Binding of a Protein to a Ligand: 0xygen-Binding Proteins Oxygen Can Bind to a Heme Prosthetic Group Myoglobin Has a Single Binding Site for Oxygen Protein-Ligand Interactions Can Be Described Quantitatively The Immune Response Features a Specialized Array of Cells and Proteins 170 Artibodies Have TWo Identical Antigen-Binding Sites 171 Antibodies Bind Tightly and Specifically to Antigen 173 The Antibody-Antigen Interaction Is the Basis for a Variety of Important Analytical Procedures I73 5.3 Protein lnteractions Modulated by (hemical Energy: Actin, Myosin, and Molecular Motors The Major Proteins of Muscle Are Myosin and Actin Additional Proteins Organize the Thin and Thick Filaments into Ordered Structures Myosin Thick Filaments Slide along Actin Thin Filaments \78 183 6.1 An lntroduction to Enzymes Most Enzymes Are Proteins Enz5rmes Are Classified by the Reactions They Catalyze 6.2 How Enzymes Work En4'rnes A-ffect Reaction Rates, Not Equilibria Reaction Rates and Equilibria Have Precise Thermod)'namic Definitions A F ew Principles Explain the Catalytic Power and Speciflcity of EnzJmres Weak Interactions between Enzyme and Substrate Are Optimized in the Tfansition State Binding Energr Contributes to Reaction Speciflcity and Catalysis Speciic Catalytic Groups Contribute to Catalysis 6.3 Enzyme Kinetics as an Approach to Understanding Mechanism Substrate Concentration A-ffects the Rate of Enz)ryne-Catalyzed Reactions The Relationship between Substrate Concentration and Reaction Rate Can Be Expressed Quantitatively 126 129 r29 t29 131 132 136 138 140 t41 t42 t43 175 t75 176 t40 183 184 191 1.92 r84 186 186 188 188 189 r45 147 153 154 r54 194 194 195
xviliContents244Box6-1TransformationsoftheMichaelis-Menten Equation:7.2PolysaccharidesSome Homopolysaccharides Are Stored197TheDouble-Reciprocal Plot245Forms of FuelKinetic Parameters Are Used to Compare EnzymeSome Homopolysaccharides Serve197Activities246Structural RolesManyEnzymes CatalyzeReactionswithTwoorSteric Factors and Hydrogen Bonding InfluenceMore Substrates200247HomopolysaccharideFoldingPre-Steady StateKinetics Can ProvideBacterial and Algal Cell Walls Contain Structural201EvidenceforSpecific ReactionSteps249HeteropolysaccharidesEnzymes Are Subject to Reversible orGlycosaminoglycans Are Heteropolysaccharides201IrreversibleInhibition249ofthe Extracellular MatrixBox 6-2Kinetic Tests forDetermining Inhibition202Mechanisms7.3Glycoconjugates:Proteoglycans,Glycoproteins204EnzymeActivityDepends on pH252and GlycolipidsProteoglycans Are Glycosaminoglycan-Containing2056.4Examplesof EnzymaticReactionsMacromolecules of the Cell Surfaceand252Extracellular MatrixThe Chymotrypsin Mechanism Involves Acylation205GlycoproteinsHaveCovalentlyAttachedand Deacylation of a Ser Residue255OligosaccharidesBox6-3Evidencefor Enzyme-TransitionStateGlycolipids and Lipopolysaccharides Are210Complementarity256MembraneComponentsHexokinase Undergoes Induced Fit on212Substrate Binding7.4Carbohydrates as Informational Molecules:The Enolase Reaction Mechanism Requires257The Sugar Code213Metal lonsLectinsAreProteinsThatReadtheSugarLysozyme Uses Two Successive Nucleophilic258Code and Mediate ManyBiological Processes213Displacement ReactionsLectin-Carbohydrate Interactions Are HighlyAnUnderstandingof EnzymeMechanismDrives261Specificand Often Polyvalent216Important Advances in Medicine2637.5Working with Carbohydrates2206.5RegulatoryEnzymesAllosteric Enzymes UndergoConformational2718Nucleotides and Nucleic Acids220Changes in Response to Modulator BindingInManyPathways,Regulated StepsAre2718.1SomeBasics221Catalyzed byAllostericEnzymesNucleotidesandNucleicAcidsHaveTheKinetic Properties of Allosteric Enzymes271222CharacteristicBases andPentosesDiverge from Michaelis-Menten BehaviorPhosphodiester Bonds Link SuccessiveSome Enzymes are Regulated by Reversible274Nucleotides in Nucleic AcidsCovalent Modification223The Properties of Nucleotide Bases Affect thePhosphorylGroups Affect the Structure and276Three-DimensionalStructureof NucleicAcids224Catalytic Activity of EnzymesMultiple Phosphorylations Allow Exquisite2778.2NudeicAcidStructure225Regulatory ControlDNA Is a DoubleHelix that Stores GeneticSomeEnzymes and OtherProteins Are Regulated278Informationby Proteolytic Cleavage of an Enzyme Precursor 226DNACanOccurinDifferentThree-DirnensionalSomeRegulatoryEnzymes UseSeveral Regulatory280Forms227Mechanisms281Certain DNA Sequences Adopt Unusual Structures283MessengerRNAs CodeforPolypeptideChainsManyRNAs Have MoreComplexThree-Dimensional235Carbohydrates and Glycobiology284Structures7.1Monosaccharides and Disaccharides2352878.3NucleicAcid ChemistryThe Two Families of Monosaccharides Are287Double-Helical DNA and RNA Can Be Denatured236Aldoses and KetosesNucleic Acids from Different Species Can236Monosaccharides Have Asymmetric Centers288Form HybridsThe Common Monosaccharides Have CyclicNucleotides and Nucleic Acids Undergo238Structures289NonenzymaticTransformationsOrganisms Contain a Variety of Hexose Derivatives240292SomeBasesofDNAAreMethylated241MonosaccharidesAre Reducing AgentsThe Sequences of Long DNA Strands Can BeBox7-1Medicine:BloodGlucoseMeasurements inthe292Determined241DiagnosisandTreatmentof DiabetesThe Chemical Synthesis of DNA Has BeenDisaccharides Contain a Glycosidic Bond243294Automated
f .J Ivrrl Contents Box 6-1 Transformations of the Michaelis-Menten Equation: The Double-Reciprocal Plot Kinetic Parameters Are Used to Compare Enzyme Activities Many Enzymes Cata\ze Reactions with TWo or More Substrates Pre-Steady State Kinetics Can Provide Evidence for Specific Reaction Steps Erzy'rnes Are Subject to Reversible or Irreversible Inhibition Box 6-2 Kinetic Tests for Determining lnhibition Mechanisms EnzSrme Activity Depends on pH 6.4 Examples of Enzymatic Reactions The Chymotrypsin Mechanism Involves Acylation and Deacyla[ion of a Ser Residue Box 6-3 Evidence for Enzyme-Transition State Complementadty Hexokinase Undergoes Induced Fit on Substrate Binding The Enolase Reaction Mechanism Requires Metal Ions Lysozlme Uses TWo Successive Nucleophilic Displacement Reactions An Understanding of Enzyme Mechanism Drives Important Advances in Medicine 5.5 Regulatory Enzymes A-llosteric Enz)rmes Undergo Conformational Changes in Response to Modulator Binding In Many Pathways, Regulated Steps Are Catalyzed by Allosteric Enzymes The Kinetic Properties of Allosteric Enz;'rnes Diverge from Michaelis-Menten Behavior Some Enz5.rnes are Regulated by Reversible Covalent Modi-fication Phosphoryl Groups Affect the Structure and Catalytic Activity of En4rnes Multiple Phosphorylations Allow Exquisite Regulatory Controi Some Erz;'rnes and Other Proteins Are Regulated by Proteolltic Cleavage of an Enz5rme Precursor Some Regulatory Enzy.rnes Use Several Regulatory Mechanisms 7 Carbohydrates andGlycobiology 7.1 Monosaccharides and Disaccharides The TWo Families of Monosaccharides Are Aldoses and Ketoses Monosaccharides Have As].'rnmetric Centers The Common Monosaccharides Have Cyclic Structures Organisms Contain a Variety of Hexose Derivatives Monosaccharides Are Reducing Agents Box 7-1 Medicine: Blood Glucose Measurements in the Diagnosis and Treatment of Diabetes Disaccharides Contain a Glycosidic Bond 197 7.2 Polysaccharides 244 Some Homopolysaccharides Are Stored Forms of Fuel 245 Some Homopolysaccharides Serve Structural Roles 246 Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding 247 Bacterial and Algal Cell Walls Contain Structural Heteropolysaccharides 249 Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix 249 7.3 6lycoconju gates: Proteoglyca ns, Glycoproteins, and Glycolipids 252 Proteo$ycans Are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and Extracellular Matrix 252 Glycoproteins Have Covalently Attached Oligosaccharides 255 Glycolipids and Lipopolysaccharides Are Membrane Components 256 7.4 (arbohydrates as Informational Molecules: The Sugar(ode 257 Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes 258 Lectin-Carbohydrate Interactions Are Highly Speciflc and Often Pollvalent 26I 7.5 Working with Carbohydrates 263 8 Nucleotides and Nucleic Arids t97 201 20r 202 204 205 205 210 2\2 213 213 216 220 220 227 235 271 221 222 223 224 8.1 Some Basics Nucleotides and Nucleic Acids Have Characteristic Bases and Pentoses Phosphodiester Bonds Link Successive Nucleotides in Nucleic Acids 271 271 .tt7 ^ The Properties of Nucleotide Bases Affect the Three-Dimensional Structure of Nucleic Acids 276 8.2 Nucleic Acid Structure DNA Is a Double Helix that Stores Genetic Information DNA Can Occur in Different Three-Dimensional Forms Certain DNA Sequences Adopt Unusual Structures Messenger RNAs Code for Po\peptide Chains Many RNAs Have More Complex Three-Dimensional Structures 8.3 Nucleic Acid Chemistry Double-Helical DNA and RNA Can Be Denatured Nucleic Acids from Different Soecies Can Form Hybrids Nucleotides and Nucleic Acids Undergo Nonenzl'rnatic Tlansformations Some Bases of DNA Are Methylated The Sequences of Long DNA Strands Can Be Determined The Chemical Synthesis of DNA Has Been Automated 277 278 23s 236 236 238 240 24r 280 28r 283 284 287 287 289 292 292 294 241 243
ContentsXIx8.4 Other Functions of Nucleotides296347Box10-1SpermWhales:Fatheadsof theDeepNucleotides Carry Chemical Energy in Cells296Partial Hydrogenation of Cooking Oils Produces347AdenineNucleotides Are Components of ManyTrans Fatty Acids297Waxes Serve as Energy Stores and Water Repellents 349Enzyme CofactorsSome Nucleotides Are Regulatory Molecules29834910.2Structural Lipids in MembranesGlycerophospholipids Are Derivatives of350Phosphatidic Acid303DNA-Based Information TechnologiesSSome Glycerophospholipids Have Ether-Linked350FattyAcids9.1DNA Cloning:The Basics304352Chloroplasts Contain Galactolipidsand Sulfolipids352Restriction Endonucleases and DNA LigaseArchaeaContainUniqueMembraneLipids352YieldRecombinantDNA304SphingolipidsAreDerivativesofSphingosineCloningVectorsAllowAmplificationof InsertedSphingolipids at Cell Surfaces Are Sites of354DNASegments307Biological RecognitionSpecificDNA SequencesAreDetectablebyPhospholipids and Sphingolipids Are Degraded355Hybridization310inLysosomes355Expression of ClonedGenes ProducesSterols Have Four Fused Carbon RingsLarge Quantities of Protein312Box10-2Medicine:Abnormal AccumulationsofAlterations inCloned Genes ProduceModified356Membrane Lipids:Some Inherited Human DiseasesProteins312357Terminal Tags Provide Binding Sites for Affinity10.3LipidsasSignals,Cofactors,andPigmentPurification313Phosphatidylinositols and Sphingosine Derivatives357ActasIntracellularSignals9.2FromGenestoGenomes315358Eicosanoids Carry Messages toNearby CellsDNA Libraries Provide Specialized Catalogs of359Steroid Hormones Carry Messages between TissuesGeneticInformation315Vascular Plants Produce Thousands of VolatileThePolymeraseChainReactionAmplifes Specific359Signals317DNA Sequences360Vitamins A and D Are Horrnone PrecursorsGenorme Sequences Provide the UltimateVitanins E and K and the Lipid Quinones Are317Genetic Libraries361Oxidation-Reduction CofactorsBox 9-1APotent Weapon inForensic Medicine319Dolichols Activate Sugar Precursors for362Biosynthesis9.3FromGenomestoProteomes324Many Natural Pigments Are Lipidic362Sequence or Structural RelationshipsConjugated DienesProvide Information on ProteinFunction32436310.4Working with LipidsCellular Expression Patterns Can Reveal the363Lipid Extraction Requires Organic SolventsCellular Function of a Gene325AdsorptionChronatography Separates LipidsDetection of Protein-Protein Interactions Helps to364of Different PolarityDefine Cellular and MolecularFunction328Gas-Liquid Chromatography Resolves Mixtures365of Volatile Lipid Derivatives9.4 Genome Alterations and New ProductsSpecific Hydrolysis Aids in Determination of330of Biotechnology365Lipid StructureABacterial Plant ParasiteAids Cloning in Plants330Mass SpectrornetryReveals CompleteManipulation of Animal Cell Genomes Provides365Lipid StructureInformation on Chromosome Structure andLipidomics Seeks to Catalog All Lipids and332GeneExpression365Their FunctionsBox 9-2Medicine:The HumanGenomeand Human335GeneTherapy37111 Biological Membranesand TransportNewTechnologies PromisetoExpeditetheDiscovery of NewPharmaceuticals33537211.1The Composition and Architecture of MembranesRecombinantDNATechnologyYields NewEach Type of Membrane Has CharacteristicProducts and Challenges337372Lipids and ProteinsAllBiological Membranes Share Some373Fundarmental Properties10Lipids343A Lipid Bilayer Is the Basic Structural374Elementof Membranes10.1Storage Lipids343Three Types of Mernbrane Proteins Differ in343375Fatty Acids Are Hydrocarbon DerivativesTheirAssociationwiththeMembraneTriacylglycerols Are Fatty Acid Esters of Glycerol346375Many Membrane Proteins Span the Lipid BilayerTriacylglycerols Provide Stored EnergyIntegral Proteins Are Held in the Membrane by346376and InsulationHydrophobic Interactions with Lipids
8.4 Other Functions of Nucleotides Nucleotides Carry Chemical Energy in Ceils Adenine Nucleotides Are Components of Marry EnzSrme Cofactors Some Nucleotides Are Regulatory Molecules 9 DNA-Based Information Terhnologies 3CI3 9.1 DNA Cloning:The Basics 304 Restriction Endonucleases and DNA Ligase Yield Recombinant DNA 304 Cloning Vectors Allow Ampliflcation of Inserted DNA Segments 307 Speci-flc DNA Sequences Are Detectable by Hybridization 310 Expression of Cloned Genes Produces Large Quantities of Protein 3I2 Alterations in Cloned Genes Produce Modified Proteins 3I2 Terminal Tags Provide Binding Sites for Affinity Purification 313 9.2 From Genes to Genomes 315 DNA Libraries Provide Specialized Cataiogs of Genetic Information 315 The Polymerase Chain Reaction Amplifles Speciic Box 10-1 Sperm Whales: Fatheads of the Deep 347 Partial Hydrogenation of Cooking Oils Produces Tfans Fatty Acids 347 Waxes Serve as Energy Stores and Water Repellents 349 10.2 Structural Lipids inMembranes 349 Glycerophospholipids Are Derivatives of Phosphatidic Acid 350 Some Glycerophospholipids Have Ether-Linked Fatty Acids 350 Ctrloroplasts Contain Galactolipids and Sulfolipids 352 Archaea Contain Unique Membrane Lipids 352 Sphingolipids Are Derivatives of Sphingosine 352 Sphingolipids at Cell Surfaces Are Sites of Biological Recognition 354 Phospholipids and Sphingolipids Are Degraded In LySOSOmeS Sterols Have Four Fused Carbon Rhgs Box10-2 Medicine; Abnormal Accumulations of Membrane Lipids:Some Inhrited Human Diseases 10.3 Lipids as Signals, Cofactors, andPigments Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals Eicosanoids Carry Messages to Nearby Cells Steroid Hormones Carry Messages between Tissues Vascular Plants Produce Thousands of Volatile Signals Vitamins A and D Are Hormone Precursors Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors Dolichols Activate Sugar Precursors for Biosyrrthesis Many Natural Pigments Are Lipidic Conjugated Dienes 10.4 Working with Lipids 363 Lipid Extraction Requires Organic Solvents 363 Adsorption Chromatography Separates Lipids of Different Polarity 364 Gas-Liquid Chromatography Resolves Mixtures of Volatile Lipid Derivatives 365 Speciic Hydrolysis Aids in Determination of Lipid Structure 365 Mass Spectrometry Reveals Complete Lipid Structure 365 Lipidomics Seeks to Catalog All Lipids and Their Functions 365 11 Biological Membranes and Transport 371 11.1 The (omposition and Architecture of Membranes 372 Each Tlpe of Membrane Has Characteristic Lipids and Proteins 372 All Biological Membranes Share Some Fundamental Properties 373 A Lipid Bilayer Is the Basic Structural Element of Membranes Three T$pes of Membrane Proteins Differ in Their Association with the Membrane Many Membrane Proteins Span the Lipid Bilayer Integral Proteins Are Held in the Membrane by Hydrophobic Interactions with Lipids 296 296 to7 298 .JDi) 355 356 357 357 rJD'' 359 359 360 361 DNA Sequences Genome Sequences Provide the Ultimate Genetic Libraries Box 9-1 A PotentWeapon in Forensic Medicine 9.3 From Genomes to Proteomes Sequence or Structural Relationships Provide Information on Protein Function Cellular Expression Patterns Can Reveal the Cellular Function of a Gene Detection of Protein-Protein Interactions Helps to Define Cellular and Molecular Function 9.4 Genome Alterations and New Products ofBiotechnology 330 A Bacterial Plant Parasite Aids Cloning in Plants 330 Manipulation of Animal Cell Genomes Provides Information on Chromosome Structure and Gene Expression 332 Box9-2 Medicine:The Human Genome and Human GeneTherapy 335 New Technologies Promise to Expedite the Discovery of New Pharmaceuticals 335 Recombinant DNA Technology Yields New Products and Challenges 337 10 Lipids 343 10.1 Storage Lipids Fatty Acids Are Hydrocarbon Derivatives Tfiacylglycerols Are Fatty Acid Esters of Glyceroi Ttiacylglycerols Provide Stored Energy and Insulation Jl r 317 319 324 e.) A 325 328 343 r)4r) J40 .14r, ary^ QNF Q.7 tr .t 1 0