Contents in Brief Contents Preface 1 The Foundations of Biochemistry 1 The Foundations of Biochemistry 1 1.1 Cellular Foundations I STRUCTURE AND CATALYSIS 45 Celsrehed PnctoUnits 2 Water 3 Amino Acids,Peptides,and Proteins s of energy 4 The Three-Dimensional Structure of Proteins 115 and Bio Protein Function 157 Features but iffer in Importan 1 243 Organelle Nucleotides and Nucleic Acids 281 9 DNA-Based Information Technologie 313 89 10Lipids 357 Interactions among Molecules porta Membranes and Transport 12 Biosignaling 433 1.2 Chemical Foundations 11 Are Co nds of Carbon with a II BIOENERGETICS AND METABOLISM 501 12 ain a Universal Set of 13 Bioenergetics and Biochemical Reaction Types 505 14 and the Weight,Molecular Mass,and 543 Their Corect Units 14 15 587 the Majo 16 The CitricAcid Cycle 633 onfguration and Confo 16 17 Fattu Acid Catabolism 667 695 18 orylationan 19 731 20 Carbohydrate Biosynthesis in Plants and Bacteria 1.3 Physical Foundatic 20 799 21 Lipid Biosynthesis 833 ady tings 21 22 Biosunthesis of Amino Acids Nucleotides Org sform Energy and Matter from Thei and Related Molecules 21 22 23 Hormonal Regulation and Integration of Energy for Mammalian Metabolism 929 22 d Maintaining Order Requires Work III INFORMATION PATHWAYS 977 24 Genes and Chromosomes 979 1 endency 25 DNA Metabolism 1009 to Pro ed S usly 26 RNA Metabolism 1057 27 Protein Metabolism 1103 Economy 28 28 Regulation of Gene Expression 1155 1.4 Genetic Foundations 29 A5-1 G-1 30 The Structure Of DNA A Allows for I s Replication and 30 Index The Li inear Sequence in DNA Encodes Proteins with hree 30
Preface vi 1 The Foundations of Biochemistry 1 I STRUCTURE AND CATALYSIS 45 2 Water 47 3 Amino Acids, Peptides, and Proteins 75 4 The Three-Dimensional Structure of Proteins 115 5 Protein Function 157 6 Enzymes 189 7 Carbohydrates and Glycobiology 243 8 Nucleotides and Nucleic Acids 281 9 DNA-Based Information Technologies 313 10 Lipids 357 11 Biological Membranes and Transport 385 12 Biosignaling 433 II BIOENERGETICS AND METABOLISM 501 13 Bioenergetics and Biochemical Reaction Types 505 14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 543 15 Principles of Metabolic Regulation 587 16 The Citric Acid Cycle 633 17 Fatty Acid Catabolism 667 18 Amino Acid Oxidation and the Production of Urea 695 19 Oxidative Phosphorylation and Photophosphorylation 731 20 Carbohydrate Biosynthesis in Plants and Bacteria 799 21 Lipid Biosynthesis 833 22 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 881 23 Hormonal Regulation and Integration of Mammalian Metabolism 929 III INFORMATION PATHWAYS 977 24 Genes and Chromosomes 979 25 DNA Metabolism 1009 26 RNA Metabolism 1057 27 Protein Metabolism 1103 28 Regulation of Gene Expression 1155 Abbreviated Solutions to Problems AS-1 Glossary G-1 Credits C-1 Index I-1 xv Contents in Brief 1 The Foundations of Biochemistry 1 1.1 Cellular Foundations 2 Cells Are the Structural and Functional Units of All Living Organisms 3 Cellular Dimensions Are Limited by Diffusion 3 There Are Three Distinct Domains of Life 3 Organisms Differ Widely in Their Sources of Energy and Biosynthetic Precursors 4 Bacterial and Archaeal Cells Share Common Features but Differ in Important Ways 4 Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study 6 The Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic 8 Cells Build Supramolecular Structures 9 In Vitro Studies May Overlook Important Interactions among Molecules 9 1.2 Chemical Foundations 11 Biomolecules Are Compounds of Carbon with a Variety of Functional Groups 12 Cells Contain a Universal Set of Small Molecules 14 BOX 1–1 Molecular Weight, Molecular Mass, and Their Correct Units 14 Macromolecules Are the Major Constituents of Cells 15 Three-Dimensional Structure Is Described by Configuration and Conformation 16 BOX 1–2 Louis Pasteur and Optical Activity: In Vino, Veritas 18 Interactions between Biomolecules Are Stereospecific 19 1.3 Physical Foundations 20 Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings 21 Organisms Transform Energy and Matter from Their Surroundings 21 BOX 1–3 Entropy: Things Fall Apart 22 The Flow of Electrons Provides Energy for Organisms 22 Creating and Maintaining Order Requires Work and Energy 22 Energy Coupling Links Reactions in Biology 24 Keq and DG8 Are Measures of a Reaction’s Tendency to Proceed Spontaneously 25 Enzymes Promote Sequences of Chemical Reactions 27 Metabolism Is Regulated to Achieve Balance and Economy 28 1.4 Genetic Foundations 29 Genetic Continuity Is Vested in Single DNA Molecules 30 The Structure of DNA Allows for Its Replication and Repair with Near-Perfect Fidelity 30 The Linear Sequence in DNA Encodes Proteins with Three-Dimensional Structures 30 Contents FMTOC.indd Page xv 10/10/12 7:30 AM user-F408 /Users/user-F408/Desktop
Contents 1.5 Evolutionary Foundations 2.4 Water as a Reactant 69 Changes in the Hereditary Instructions Allow 2.5 The Fitness of the Aqueous Environment for Arose by Chemical Evolution Living Organisms 69 May Have Been the 34 3 Amino Acids,Peptides,and Proteins 75 The First Cel PyUeiiorganicue 3.1 Amino Acids nSaSslohedonsnplterPaeursors Share C ral Features 76 36 The Amino Acid Residues in Proteins Are tomy Reveals Evolutionary 37 Ami Be Classifed by R Group 哈 BOX3-1 METHODS:Absorption of Light by Molecules:The 38 80 39 STRUCTURE AND CATALYSIS 45 2 Water 47 Amino Acids Amino Acids Differ in Their Acid-Base Properties 84 2.1 Weak Interactions in Aqueous Systems 3.2 Peptides and Proteins 85 Hydrogen Bonding Gives Water Its Unusual Peptides Are Chains of Amino Acids Water Forms Hydr 49 Peptides Can Be Distinguished by Their lonization Solut Biologically Active Peptides and Polypeptides Occur Contain Chemical Groups Other Than Amino Acids 89 51 3.3 Working with Proteins 89 des in of Water van der rAre 51 Proteins Can Be Separated and Purified Proteins Can Be Separated and Characterized by Weak interactions Are Crucial to Macromolecu 53 Unseparated Proteins Can Be Quantified 54 3.4 96 Acid Sequenc 97 2.2 lonization of Water,Weak Acids,and Weak Bases 58 58 The Pure Water Is Slightly lonized 97 er Is Expressed by an 59 nAltemative Method to 98 Weak Acids and B 60 100 s Have Characteristic Acid Small Peptides and Proteins Can Be Chemically of Weak Acids 10e ces Provide Important 2.3 Buffering against pH Changes in Biological Pr Biochemicalind 104 Elucidate the Histor Systems 63 of Life on Earth Buffers Are Mixtur BOX 3-2 ConsensusSequences and Sequence Logos 105 The sselbalch Equation Relates 64 64 4 The three-Dimensional structure 65 of Proteins 115 4.1 Overview of Protein Structure 115 A Protein's Conformation Is Stabilized Largely by 68 eak I The
1.5 Evolutionary Foundations 32 Changes in the Hereditary Instructions Allow Evolution 32 Biomolecules First Arose by Chemical Evolution 33 RNA or Related Precursors May Have Been the First Genes and Catalysts 34 Biological Evolution Began More Than Three and a Half Billion Years Ago 35 The First Cell Probably Used Inorganic Fuels 35 Eukaryotic Cells Evolved from Simpler Precursors in Several Stages 36 Molecular Anatomy Reveals Evolutionary Relationships 37 Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes 38 Genomic Comparisons Have Increasing Importance in Human Biology and Medicine 39 I STRUCTURE AND CATALYSIS 45 2 Water 47 2.1 Weak Interactions in Aqueous Systems 47 Hydrogen Bonding Gives Water Its Unusual Properties 47 Water Forms Hydrogen Bonds with Polar Solutes 49 Water Interacts Electrostatically with Charged Solutes 50 Entropy Increases as Crystalline Substances Dissolve 51 Nonpolar Gases Are Poorly Soluble in Water 51 Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water 51 van der Waals Interactions Are Weak Interatomic Attractions 53 Weak Interactions Are Crucial to Macromolecular Structure and Function 54 Solutes Affect the Colligative Properties of Aqueous Solutions 55 2.2 Ionization of Water, Weak Acids, and Weak Bases 58 Pure Water Is Slightly Ionized 58 The Ionization of Water Is Expressed by an Equilibrium Constant 59 The pH Scale Designates the H and OH Concentrations 60 Weak Acids and Bases Have Characteristic Acid Dissociation Constants 61 Titration Curves Reveal the pKa of Weak Acids 62 2.3 Buffering against pH Changes in Biological Systems 63 Buffers Are Mixtures of Weak Acids and Their Conjugate Bases 64 The Henderson-Hasselbalch Equation Relates pH, pKa, and Buffer Concentration 64 Weak Acids or Bases Buffer Cells and Tissues against pH Changes 65 Untreated Diabetes Produces Life-Threatening Acidosis 67 BOX 2–1 MEDICINE: On Being One’s Own Rabbit (Don’t Try This at Home!) 68 2.4 Water as a Reactant 69 2.5 The Fitness of the Aqueous Environment for Living Organisms 69 3 Amino Acids, Peptides, and Proteins 75 3.1 Amino Acids 76 Amino Acids Share Common Structural Features 76 The Amino Acid Residues in Proteins Are L Stereoisomers 78 Amino Acids Can Be Classified by R Group 78 BOX 3–1 METHODS: Absorption of Light by Molecules: The Lambert-Beer Law 80 Uncommon Amino Acids Also Have Important Functions 81 Amino Acids Can Act as Acids and Bases 81 Amino Acids Have Characteristic Titration Curves 82 Titration Curves Predict the Electric Charge of Amino Acids 84 Amino Acids Differ in Their Acid-Base Properties 84 3.2 Peptides and Proteins 85 Peptides Are Chains of Amino Acids 85 Peptides Can Be Distinguished by Their Ionization Behavior 86 Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes and Compositions 87 Some Proteins Contain Chemical Groups Other Than Amino Acids 89 3.3 Working with Proteins 89 Proteins Can Be Separated and Purified 89 Proteins Can Be Separated and Characterized by Electrophoresis 92 Unseparated Proteins Can Be Quantified 95 3.4 The Structure of Proteins: Primary Structure 96 The Function of a Protein Depends on Its Amino Acid Sequence 97 The Amino Acid Sequences of Millions of Proteins Have Been Determined 97 Protein Chemistry Is Enriched by Methods Derived from Classical Polypeptide Sequencing 98 Mass Spectrometry Offers an Alternative Method to Determine Amino Acid Sequences 100 Small Peptides and Proteins Can Be Chemically Synthesized 102 Amino Acid Sequences Provide Important Biochemical Information 104 Protein Sequences Can Elucidate the History of Life on Earth 104 BOX 3–2 Consensus Sequences and Sequence Logos 105 4 The Three-Dimensional Structure of Proteins 115 4.1 Overview of Protein Structure 115 A Protein’s Conformation Is Stabilized Largely by Weak Interactions 116 The Peptide Bond Is Rigid and Planar 117 xvi Contents FMTOC.indd Page xvi 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
Contents xvii 4.2 Protein Secondaru Structure 11g 165 The a Helix Isa Common Protein Secondary 167 nce Affects Stability of the a Helix anisms for 167 Chainsinto Sheets 189 Diheral Angles Sicke-Cenem Disease of res Can Be Assessed by Hemoglobin 172 Circular dichroism 124 5.2 Complementary Interactions between Proteins 43PoienetanandQuetm5ite 125 174 nction nse Features a specialized hemical Eng 127 174 Bind Tightly and Specifically to 今 Ant 130 ntige Myoglobin Provi arly Clues about the tein Structure 178 B0X4-4 The Pro Data Bank Globuar Proteins Have a Variety of Tertiary 5.3 Protein Interactions Modulated by Chemical 133 Energy:Actin,Myosin,and Molecular Motors 179 B0X4-5 METHODS:Methods for Detemining the Three- 134 179 fica the tein Structural 138 181 sinThick Filaments Slide along Actin 140 Thin Filament 182 141 6 Enzymes 189 18g 4.4 Protein Denaturation and Folding 143 Loss of Protein Structure Results in Loss 190 Amino Acid Sequence Determines Tertiary 143 190 pwise Process 14 6.2 How Enzymes Work 192 19 146 Basis for a Wide Range of Human Genetic 194 Death by Misfolding:The Prio Diseases of Enzy 194 Are Ontimized in the T dSubstrate 5 Protein Function 157 195 Bind gyContributes to Reaction Specificity 5.1 Reversible Binding of a Protein to a Ligand: Specific Catalytic Groups Contribute to Catalysis 199 Oxygen-Binding Proteins 6.3 Enzyme Kinetics as an Approach to eins Understanding Mechanism 200 a Single Bin r Ox s the Rate of 200 The Aftects How Li and Reaction Rate an aion Qua 202 obn Subunits Are Structurally milar to s Are Used to Compare Enzym gosa Structura Changeon 163 BOX6-1 Tra 203 of the Mic lis-Menter 163 Equation:The 204
4.2 Protein Secondary Structure 119 The Helix Is a Common Protein Secondary Structure 120 Amino Acid Sequence Affects Stability of the Helix 121 BOX 4–1 METHODS: Knowing the Right Hand from the Left 121 The Conformation Organizes Polypeptide Chains into Sheets 123 Turns Are Common in Proteins 123 Common Secondary Structures Have Characteristic Dihedral Angles 123 Common Secondary Structures Can Be Assessed by Circular Dichroism 124 4.3 Protein Tertiary and Quaternary Structures 125 Fibrous Proteins Are Adapted for a Structural Function 125 BOX 4–2 Permanent Waving Is Biochemical Engineering 127 BOX 4–3 MEDICINE: Why Sailors, Explorers, and College Students Should Eat Their Fresh Fruits and Vegetables 128 Structural Diversity Reflects Functional Diversity in Globular Proteins 130 Myoglobin Provided Early Clues about the Complexity of Globular Protein Structure 131 BOX 4–4 The Protein Data Bank 132 Globular Proteins Have a Variety of Tertiary Structures 133 BOX 4–5 METHODS: Methods for Determining the ThreeDimensional Structure of a Protein 134 Protein Motifs Are the Basis for Protein Structural Classification 138 Protein Quaternary Structures Range from Simple Dimers to Large Complexes 140 Some Proteins or Protein Segments Are Intrinsically Disordered 141 4.4 Protein Denaturation and Folding 143 Loss of Protein Structure Results in Loss of Function 143 Amino Acid Sequence Determines Tertiary Structure 144 Polypeptides Fold Rapidly by a Stepwise Process 144 Some Proteins Undergo Assisted Folding 146 Defects in Protein Folding Provide the Molecular Basis for a Wide Range of Human Genetic Disorders 148 BOX 4–6 MEDICINE: Death by Misfolding: The Prion Diseases 150 5 Protein Function 157 5.1 Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins 158 Oxygen Can Bind to a Heme Prosthetic Group 158 Globins Are a Family of Oxygen-Binding Proteins 159 Myoglobin Has a Single Binding Site for Oxygen 159 Protein-Ligand Interactions Can Be Described Quantitatively 159 Protein Structure Affects How Ligands Bind 162 Hemoglobin Transports Oxygen in Blood 163 Hemoglobin Subunits Are Structurally Similar to Myoglobin 163 Hemoglobin Undergoes a Structural Change on Binding Oxygen 163 Hemoglobin Binds Oxygen Cooperatively 165 Cooperative Ligand Binding Can Be Described Quantitatively 167 Two Models Suggest Mechanisms for Cooperative Binding 167 BOX 5–1 MEDICINE: Carbon Monoxide: A Stealthy Killer 168 Hemoglobin Also Transports H and CO2 169 Oxygen Binding to Hemoglobin Is Regulated by 2,3-Bisphosphoglycerate 171 Sickle-Cell Anemia Is a Molecular Disease of Hemoglobin 172 5.2 Complementary Interactions between Proteins and Ligands: The Immune System and Immunoglobulins 174 The Immune Response Features a Specialized Array of Cells and Proteins 174 Antibodies Have Two Identical Antigen-Binding Sites 175 Antibodies Bind Tightly and Specifically to Antigen 177 The Antibody-Antigen Interaction Is the Basis for a Variety of Important Analytical Procedures 178 5.3 Protein Interactions Modulated by Chemical Energy: Actin, Myosin, and Molecular Motors 179 The Major Proteins of Muscle Are Myosin and Actin 179 Additional Proteins Organize the Thin and Thick Filaments into Ordered Structures 181 Myosin Thick Filaments Slide along Actin Thin Filaments 182 6 Enzymes 189 6.1 An Introduction to Enzymes 189 Most Enzymes Are Proteins 190 Enzymes Are Classified by the Reactions They Catalyze 190 6.2 How Enzymes Work 192 Enzymes Affect Reaction Rates, Not Equilibria 192 Reaction Rates and Equilibria Have Precise Thermodynamic Definitions 194 A Few Principles Explain the Catalytic Power and Specificity of Enzymes 194 Weak Interactions between Enzyme and Substrate Are Optimized in the Transition State 195 Binding Energy Contributes to Reaction Specificity and Catalysis 197 Specific Catalytic Groups Contribute to Catalysis 199 6.3 Enzyme Kinetics as an Approach to Understanding Mechanism 200 Substrate Concentration Affects the Rate of Enzyme-Catalyzed Reactions 200 The Relationship between Substrate Concentration and Reaction Rate Can Be Expressed Quantitatively 202 Kinetic Parameters Are Used to Compare Enzyme Activities 203 BOX 6–1 Transformations of the Michaelis-Menten Equation: The Double-Reciprocal Plot 204 Contents xvii FMTOC.indd Page xvii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
kwiⅷi Contents 206 257 Pre Bacterial an Algal Cel Walls Contain Structural 207 259 Gly B0X6-Kinetic Tests for Detenng 20% 260 209 7.3 Glycoconjugates:Proteoglycans,Glycoproteins, EDICNE:Curing African Sleeping Sickness and Gly Prot Enzyme Activity Depends on pH 6.4 Examples of Enzymatic Reactio 214 264 Glycoproteins Have Covalently Attached lation of er Residue 214 266 lysaccharides Are ote 268 ons 218 Hex s Und goes Induced Fit on 7.4 Carbohydrates Moleue 219 269 The Eno e Reaction Mechanism Requires meUses Two Successive Nucleophilic 20 gical Processe 269 220 s Are Highl 272 An 224 7.5 Working with Carbohydrates 274 226 8 Nucleotides and NucleicAcids 281 2 281 2 d Nucleic Acids Have Characteristic Bases and Pe 228 Phe s Link Successive Nucleotides 281 284 ct the Structure and 29 Th Multiple Phospho ylations Allow Exquisite T-esuucure A cids 286 8.2 Nucleic Acid Structure 西 DNA Is a Double Helix That Stores Genetic 231 288 Leads to Blood Coagulation 232 DNACan Occurn Different Three-Dimensiona Mechanisms y Enzymes Use Several Regulatory es Adopt Unusual Structures Messe nger RNAS C ode for Polypeptide Chains 7 Carbohydrates and Glycobiology 243 Three-pimensional Structures 294 243 8.3 NucleicAcid Chemistry Are 29 297 Aldos and Ke 298 and Nucleic Acids Undergo Structures No -MEDICINE:Measurements in the Base s of D o DNA Suands Can Be Diabete mine 302 The Che idic Bond Automated Synthesis of DNA Has Been 304 B0X7-Sugar is Sweet,and So Are …afew0 ther Things254 7.2 Polysaccharides 8.4 Other Functios of Nucleotides 306 254 06 atory Molecules
xviii Contents Many Enzymes Catalyze Reactions with Two or More Substrates 206 Pre–Steady State Kinetics Can Provide Evidence for Specific Reaction Steps 207 Enzymes Are Subject to Reversible or Irreversible Inhibition 207 BOX 6–2 Kinetic Tests for Determining Inhibition Mechanisms 209 BOX 6–3 MEDICINE: Curing African Sleeping Sickness with a Biochemical Trojan Horse 211 Enzyme Activity Depends on pH 212 6.4 Examples of Enzymatic Reactions 214 The Chymotrypsin Mechanism Involves Acylation and Deacylation of a Ser Residue 214 An Understanding of Protease Mechanisms Leads to New Treatments for HIV Infections 218 Hexokinase Undergoes Induced Fit on Substrate Binding 219 The Enolase Reaction Mechanism Requires Metal Ions 220 Lysozyme Uses Two Successive Nucleophilic Displacement Reactions 220 An Understanding of Enzyme Mechanism Produces Useful Antibiotics 224 6.5 Regulatory Enzymes 226 Allosteric Enzymes Undergo Conformational Changes in Response to Modulator Binding 226 The Kinetic Properties of Allosteric Enzymes Diverge from Michaelis-Menten Behavior 227 Some Enzymes Are Regulated by Reversible Covalent Modification 228 Phosphoryl Groups Affect the Structure and Catalytic Activity of Enzymes 229 Multiple Phosphorylations Allow Exquisite Regulatory Control 230 Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor 231 A Cascade of Proteolytically Activated Zymogens Leads to Blood Coagulation 232 Some Regulatory Enzymes Use Several Regulatory Mechanisms 235 7 Carbohydrates and Glycobiology 243 7.1 Monosaccharides and Disaccharides 243 The Two Families of Monosaccharides Are Aldoses and Ketoses 244 Monosaccharides Have Asymmetric Centers 244 The Common Monosaccharides Have Cyclic Structures 245 Organisms Contain a Variety of Hexose Derivatives 249 BOX 7–1 MEDICINE: Blood Glucose Measurements in the Diagnosis and Treatment of Diabetes 250 Monosaccharides Are Reducing Agents 251 Disaccharides Contain a Glycosidic Bond 252 BOX 7–2 Sugar Is Sweet, and So Are . . . a Few Other Things 254 7.2 Polysaccharides 254 Some Homopolysaccharides Are Stored Forms of Fuel 255 Some Homopolysaccharides Serve Structural Roles 256 Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding 257 Bacterial and Algal Cell Walls Contain Structural Heteropolysaccharides 259 Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix 260 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycosphingolipids 263 Proteoglycans Are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and Extracellular Matrix 264 Glycoproteins Have Covalently Attached Oligosaccharides 266 Glycolipids and Lipopolysaccharides Are Membrane Components 268 7.4 Carbohydrates as Informational Molecules: The Sugar Code 269 Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes 269 Lectin-Carbohydrate Interactions Are Highly Specific and Often Multivalent 272 7.5 Working with Carbohydrates 274 8 Nucleotides and Nucleic Acids 281 8.1 Some Basics 281 Nucleotides and Nucleic Acids Have Characteristic Bases and Pentoses 281 Phosphodiester Bonds Link Successive Nucleotides in Nucleic Acids 284 The Properties of Nucleotide Bases Affect the Three-Dimensional Structure of Nucleic Acids 286 8.2 Nucleic Acid Structure 287 DNA Is a Double Helix That Stores Genetic Information 288 DNA Can Occur in Different Three-Dimensional Forms 290 Certain DNA Sequences Adopt Unusual Structures 291 Messenger RNAs Code for Polypeptide Chains 293 Many RNAs Have More Complex Three-Dimensional Structures 294 8.3 Nucleic Acid Chemistry 297 Double-Helical DNA and RNA Can Be Denatured 297 Nucleic Acids from Different Species Can Form Hybrids 298 Nucleotides and Nucleic Acids Undergo Nonenzymatic Transformations 299 Some Bases of DNA Are Methylated 302 The Sequences of Long DNA Strands Can Be Determined 302 The Chemical Synthesis of DNA Has Been Automated 304 8.4 Other Functions of Nucleotides 306 Nucleotides Carry Chemical Energy in Cells 306 Adenine Nucleotides Are Components of Many Enzyme Cofactors 306 Some Nucleotides Are Regulatory Molecules 308 FMTOC.indd Page xviii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
Contents xix 9 DNA-Based Information Technologies 313 SaPmceapoiptiaeBierinkad 9.1 Studying Genes and Their Products 314 314 314 Sphingol ids at Cell Surfaces Are Sites of Biologic Allow Amplification of Inserted sCan Be Expressed to Amplify Protein 321 rols Have F Ster our Fused Carbon Rings 368 ecomb s2 369 es Produces Altered 10.3 Lipids as Signals,Cofactors,and Pigments 370 sProvide Handles for Afnity Phosphatidylinositos and Sphingosine Derivatives 26 s to Nearby Cells 379 Steroid Hormones Carry M essages between BOX 9-1 METHODS:A Powerful Tool in Forensic Medicine 329 Vasc car Plants Produce Thousands of Volatile 372 9.2 Using DNA-Based Methods toUnderstand A Functio 331 Vitamins A and D Are Hormone Precursors cialized Catalogs of Genetic d the Quinones Are nformatio 374 Doli hols Activate Sugar Precursors for 333 375 ofluorescence Can Many Natural Pigments Are Lipidic Conjugated 333 376 n Interactions Can Help Elucidate 376 eal RNA Expression Patterns 93 Genomics and the human stor rption tography Separates Lipids of uencing Is Aided by New Generations 378 Gas-iqdC graphy Resolves Mixtures of ing M enomic Medicine 378 The Human Genome Contains Genes and Man 378 about Our etry Reveals Complete Lipd 378 Seeksto Catalog All Lipids and Their 347 Function 37m r Past and BOX9-3 Getting to Know the Neanderthals 350 11 Biological Membranes and Transport 385 10 Lipids 357 d Proteins 35 Some Fundamenta 8 S Are 360 er Is the Basic Structural Element of 87 360 e Proteins DifTer in Their 361 388 rane by 362 390 The 10.2 Structural Lipids in Membranes Topoloeofan nce 391 hed Lipids Anchor Some 394
Contents xix 9 DNA-Based Information Technologies 313 9.1 Studying Genes and Their Products 314 Genes Can Be Isolated by DNA Cloning 314 Restriction Endonucleases and DNA Ligases Yield Recombinant DNA 314 Cloning Vectors Allow Amplification of Inserted DNA Segments 317 Cloned Genes Can Be Expressed to Amplify Protein Production 321 Many Different Systems Are Used to Express Recombinant Proteins 322 Alteration of Cloned Genes Produces Altered Proteins 323 Terminal Tags Provide Handles for Affinity Purification 325 Gene Sequences Can Be Amplified with the Polymerase Chain Reaction 327 BOX 9–1 METHODS: A Powerful Tool in Forensic Medicine 329 9.2 Using DNA-Based Methods to Understand Protein Function 331 DNA Libraries Are Specialized Catalogs of Genetic Information 332 Sequence or Structural Relationships Provide Information on Protein Function 333 Fusion Proteins and Immunofluorescence Can Localize Proteins in Cells 333 Protein-Protein Interactions Can Help Elucidate Protein Function 334 DNA Microarrays Reveal RNA Expression Patterns and Other Information 337 9.3 Genomics and the Human Story 339 Genomic Sequencing Is Aided by New Generations of DNA-Sequencing Methods 339 BOX 9–2 MEDICINE: Personalized Genomic Medicine 340 The Human Genome Contains Genes and Many Other Types of Sequences 342 Genome Sequencing Informs Us about Our Humanity 345 Genome Comparisons Help Locate Genes Involved in Disease 347 Genome Sequences Inform Us about Our Past and Provide Opportunities for the Future 349 BOX 9–3 Getting to Know the Neanderthals 350 10 Lipids 357 10.1 Storage Lipids 357 Fatty Acids Are Hydrocarbon Derivatives 357 Triacylglycerols Are Fatty Acid Esters of Glycerol 360 Triacylglycerols Provide Stored Energy and Insulation 360 Partial Hydrogenation of Cooking Oils Produces Trans Fatty Acids 361 Waxes Serve as Energy Stores and Water Repellents 362 10.2 Structural Lipids in Membranes 362 Glycerophospholipids Are Derivatives of Phosphatidic Acid 363 Some Glycerophospholipids Have Ether-Linked Fatty Acids 364 Chloroplasts Contain Galactolipids and Sulfolipids 365 Archaea Contain Unique Membrane Lipids 365 Sphingolipids Are Derivatives of Sphingosine 366 Sphingolipids at Cell Surfaces Are Sites of Biological Recognition 367 Phospholipids and Sphingolipids Are Degraded in Lysosomes 368 Sterols Have Four Fused Carbon Rings 368 BOX 10–1 MEDICINE: Abnormal Accumulations of Membrane Lipids: Some Inherited Human Diseases 369 10.3 Lipids as Signals, Cofactors, and Pigments 370 Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals 370 Eicosanoids Carry Messages to Nearby Cells 371 Steroid Hormones Carry Messages between Tissues 372 Vascular Plants Produce Thousands of Volatile Signals 372 Vitamins A and D Are Hormone Precursors 373 Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors 374 Dolichols Activate Sugar Precursors for Biosynthesis 375 Many Natural Pigments Are Lipidic Conjugated Dienes 376 Polyketides Are Natural Products with Potent Biological Activities 376 10.4 Working with Lipids 377 Lipid Extraction Requires Organic Solvents 377 Adsorption Chromatography Separates Lipids of Different Polarity 378 Gas-Liquid Chromatography Resolves Mixtures of Volatile Lipid Derivatives 378 Specific Hydrolysis Aids in Determination of Lipid Structure 378 Mass Spectrometry Reveals Complete Lipid Structure 378 Lipidomics Seeks to Catalog All Lipids and Their Functions 379 11 Biological Membranes and Transport 385 11.1 The Composition and Architecture of Membranes 386 Each Type of Membrane Has Characteristic Lipids and Proteins 386 All Biological Membranes Share Some Fundamental Properties 387 A Lipid Bilayer Is the Basic Structural Element of Membranes 387 Three Types of Membrane Proteins Differ in Their Association with the Membrane 389 Many Membrane Proteins Span the Lipid Bilayer 390 Integral Proteins Are Held in the Membrane by Hydrophobic Interactions with Lipids 390 The Topology of an Integral Membrane Protein Can Sometimes Be Predicted from Its Sequence 391 Covalently Attached Lipids Anchor Some Membrane Proteins 394 FMTOC.indd Page xix 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop