Principles of Biochemistry · 16 The Citric Acid Cycle 567 17 Oxidation of Fatty Acids 598 18 Amino...
Transcript of Principles of Biochemistry · 16 The Citric Acid Cycle 567 17 Oxidation of Fatty Acids 598 18 Amino...
THIRD EDITIO N
Principles of Biochemistr y
David L Nelso n
Michael M . Cox
Preface ii i
I Foundations of Biochemistry 11
The Molecular Logic of Life 3
2 Cells 20
3 Biomolecules 53
4 Water 82
II Structure and Catalysis 11 35
Amino Acids, Peptides, and Proteins 11 5
6 The Three-Dimensional Structure of Proteins 15 9
7
Protein Function 203
8 Enzymes 243
9 Carbohydrates and Glycobiology 29 3
10
Nucleotides and Nucleic Acids 32 5
11
Lipids 36 3
12
Biological Membranes and Transport 38 9
13
Biosignaling 43 7
III Bioenergetics and Metabolism 48 514
Principles of Bioenergetics 49 0
15 Glycolysis and the Catabolism of Hexoses 52 7
16 The Citric Acid Cycle 567
17 Oxidation of Fatty Acids 59 8
18 Amino Acid Oxidation and the Production of Urea 62 3
19 Oxidative Phosphorylation and Photophosphorylation 65 9
20 Carbohydrate Biosynthesis 72 2
21
Lipid Biosynthesis 770
22
Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 81 8
23
Integration and Hormonal Regulation of Mammalian Metabolism 86 9
IV Information Pathways 90 524 Genes and Chromosomes 90 7
25 DNA Metabolism 93 1
26 RNA Metabolism 97 9
27 Protein Metabolism 102 0
28 Regulation of Gene Expression 107 2
29 Recombinant DNA Technology 111 9
Appendix A Common Abbreviations in the Biochemical Research Literature AP- 1
Appendix B Abbreviated Solutions to Problems AP- 4Glossary G- 1
Illustration Credits IC- 1Index I-1
Preface iii
Major Structural Features of Eukaryotic Cells 2 9The Plasma Membrane Contains Transporters and Receptors 3 0
Foundations of Biochemistry
1
Endocytosis and Exocytosis Carry Traffic across the PlasmaMembrane 3 1
1 The Molecular Logic of Life 3
The Endoplasmic Reticulum Organizes the Synthesis of Proteins andLipids 32
The Chemical Unity of Diverse Living Organisms 3
The Golgi Complex Processes and Sorts Proteins 3 3Biochemistry Explains Diverse Forms of Life in Unifying Chemical
Lyosomes Are the Sites of Degradative Reactions 3 3Terms 4
Vacuoles of Plant Cells Play Several Important Roles 3 4All Macromolecules Are Constructed from a Few Simple
Peroxisomes Destroy Hydrogen Peroxide, and Glyoxysomes Conver tCompounds 5 Fats to Carbohydrates 34Energy Production and Consumption in Metabolism 6
The Nucleus Contains the Genome 35Organisms Are Never at Equilibrium with Their Surroundings 6
Mitochondria Are the Power Plants of Aerobic Eukaryoti cMolecular Composition Reflects a Dynamic Steady State 6
Cells 3 6Organisms Transform Energy and Matter from Their
Chloroplasts Convert Solar Energy into Chemical Energy 3 7Surroundings 7
Mitochondria and Chloroplasts Probably Evolved fro mThe Flow of Electrons Provides Energy for Organisms 8
Endosymbiotic Bacteria 3 8Energy Coupling Links Reactions in Biology 9
The Cytoskeleton Stabilizes Cell Shape, Organizes the Cytoplasm ,Enzymes Promote Sequences of Chemical Reactions 11
and Produces Motion 3 9
Metabolism Is Regulated to Achieve Balance and Economy 12
The Cytoplasm Is Crowded, Highly Ordered, and Dynamic 4 2
Biological Information Transfer 13
Study of Cellular Components 42
Genetic Continuity Is Vested in DNA Molecules 13
Organelles Can Be Isolated by Centrifugation 42
The Structure of DNA Allows for Its Repair and Replication with
In Vitro Studies May Overlook Important Interactions amon gNear-Perfect Fidelity 14
Molecules 4 2
Changes in the Hereditary Instructions Allow Evolution 14
Evolution of Multicellular Organisms and Cellula rMolecular Anatomy Reveals Evolutionary Relationships 15
Differentiation 44The Linear Sequence in DNA Encodes Proteins with Three-
Viruses : Parasites of Cells 4 6Dimensional Structures 1 6
Noncovalent Interactions Stabilize Three-Dimensional
Summary 48
Further Reading 49
Problems 5 0Structures 1 7
The Physical Roots of the Biochemical World 1 8
Further Reading 19
v. 1
2 Cells 20
>sh~ a
> s~
ti:
Cellular Dimensions 21 A a
I1
n
Cells and Tissues Used in Biochemical Studies 22
v
f:
`-' {
Evolution and Structure of Prokaryotic Cells 24
+
,=:&rEscherichia co/i Is the Best-Studied Prokaryotic Cell 26
i -, ,
\ 12,-N'./iEvolution of Eukaryotic Cells 27
~i`, < y
1 \
Yom: _
Eukaryotic Cells Evolved from Prokaryotes in Several Stages 28
"
lIL 'Early Eukaryotic Cells Gave Rise to Diverse Protists 29
page 13
4 Water 82.y.
Weak Interactions in Aqueous Systems 8 2tit. Hydrogen Bonding Gives Water Its Unusual Properties 8 2
Water Forms Hydrogen Bonds with Polar Solutes 8 5
Water Interacts Electrostatically with Charged Solutes 8 6
Entropy Increases as Crystalline Substances Dissolve 8 7
•
Nonpolar Gases Are Poorly Soluble in Water 8 8
Nonpolar Compounds Force Energetically Unfavorable Changes i nt.?3 the Structure of Water 8 8
Van der Waals Interactions Are Weak Interatomic Attractions 9 0
page 62
Weak Interactions Are Crucial to Macromolecular Structure an dFunction 90
Solutes Affect the Colligative Properties of Aqueous Solutions 9 2
Box 4-1 Touch Response in Plants: An Osmotic Event 9 4
Ionization of Water, Weak Acids, and Weak Bases 9 5
3 Biomolecules 53
Pure Water Is Slightly Ionized 95
The Ionization of Water Is Expressed by an EquilibriumChemical Composition and Bonding 53
Constant 9 6Biomolecules Are Compounds of Carbon 54
Box 4-2 The /on Product of Water: Two IllustrativeFunctional Groups Determine Chemical Properties 56
Problems 9 7
Three-Dimensional Structure : Configuration and
The pH Scale Designates the H + and OH- Concentrations 97
Conformation 57
Weak Acids and Bases Have Characteristic Dissociatio n
The Configuration of a Molecule Is Changed Only by Breaking a
Constants 98
Bond 58
Titration Curves Reveal the pK a of Weak Acids 9 9
Molecular Conformation Is Changed by Rotation About Single
Buffering against pH Changes in Biological Systems 10 1Bonds 60
Buffers Are Mixtures of Weak Acids and Their ConjugateBox 3-1 Louis Pasteur and Optical Activity: In Vino, Veritas 61
Bases 102Configuration and Conformation Define Biomolecular
A Simple Expression Relates pH, pK, and Buffe rStructures 62
Concentration 10 2Interactions between Biomolecules Are Stereospecific 63
Box 4-3 Solving Problems Using the Henderson-Hasselbalc h
Chemical Reactivity 64
Equation 103
Bond Strength Is Related to the Properties of the Bonded
Weak Acids or Bases Buffer Cells and Tissues against p H
Atoms 64
Changes 104
Five General Types of Chemical Transformations Occur in
n Box 4-4 Blood, Lungs, and Buffer: The Bicarbonate Buffer
Cells 65
System 105
All Oxidation-Reduction Reactions Involve Electron Transfer 65
Water as a Reactant 10 6Carbon-Carbon Bonds Are Cleaved and Formed by Nucleophili c
Substitution Reactions 66
The Fitness of the Aqueous Environment for Living
Electron Transfers within a Molecule Produce Internal
Organisms 107
Rearrangements 67
Summary 107
Further Reading 10 8
Group Transfer Reactions Activate Metabolic Intermediates 68
Problems 109
Biopolymers Are Formed by Condensations 6 9
Macromolecules and Their Monomeric Subunits 69
II Structure and Catalysis 11 3Macromolecules Are the Major Constituents of Cells 6 9
Macromolecules Are Composed of Monomeric Subunits 70
5 Amino Acids, Peptides, and Proteins 11 5
Monomeric Subunits Have Simple Structures 70
Amino Acids 11 6
Subunit Condensation Creates Order and Requires Energy 72
Amino Acids Share Common Structural Features 11 6
Cells Have a Structural Hierarchy 72
The Amino Acid Residues in Proteins Are L Stereoisomers 11 7
Prebiotic Evolution 74
Amino Acids Can Be Classified by R Group 11 8. Box 5-1 Absorption of Light by Molecules : The Lambert-Bee r
Biomolecules First Arose by Chemical Evolution 74
Law 12 1Chemical Evolution Can Be Simulated in the Laboratory 7 4
RNA or Related Precursors May Have Been the First Genes and
Nonstandard Amino Acids Also Have Important Functions 12 1
Catalysts 75
Amino Acids Can Act as Acids and Bases 12 3
Biological Evolution Began More Than Three and a Half Billion
Amino Acids Have Characteristic Titration Curves 12 3
Years Ago 76
Titration Curves Predict the Electric Charge of Amino Acids 125
Summary 78
Further Reading 78
Amino Acids Differ in Their Acid-Base Properties 12 5
Problems 80
Peptides and Proteins 126
Peptides Are Chains of Amino Acids 126
Protein Motifs Are the Basis for Protein Structura l
Peptides Can Be Distinguished by Their Ionization Behavior 127
Classification 18 5
Biologically Active Peptides and Polypeptides Occur in a Vast
Protein Quaternary Structures Range from Simple Dimers to Larg e
Range of Sizes 127
Complexes 18 8
Polypeptides Have Characteristic Amino Acid Compositions 128
There Are Limits to the Size of Proteins 19 1
Some Proteins Contain Chemical Groups Other Than Amino
Protein Denaturation and Folding 19 1Acids 129
Loss of Protein Structure Results in Loss of Function 192There Are Several Levels of Protein Structure 129
Amino Acid Sequence Determines Tertiary Structure 19 2
Working with Proteins 130
Polypeptides Fold Rapidly by a Stepwise Process 19 3
Proteins Can Be Separated and Purified 130
* Box 6-4 Death by Misfolding: The Prion Diseases 196
Proteins Can Be Separated and Characterized
Some Proteins Undergo Assisted Folding 19 6by Electrophoresis 13 4
Unseparated Proteins Can Be Quantified 136
Summary 199
Further Reading 200Problems 200
The Covalent Structure of Proteins 13 7
The Function of a Protein Depends on Its Amino Acid
7 Protein Function 203Sequence 13 8
The Amino Acid Sequences of Numerous Proteins Have Been
Reversible Binding of a Protein to a Ligand : Oxygen-Bindin g
Determined 138
Proteins 204
• Box 5-2 Protein Homology among Species 139 Oxygen Can Be Bound to a Herne Prosthetic Group 20 4
Short Polypeptides Are Sequenced Using Automated
Myoglobin Has a Single Binding Site for Oxygen 20 6
Procedures 141
Protein-Ligand Interactions Can Be Described Quantitatively 20 6
Large Proteins Must Be Sequenced in Smaller Segments 142
Protein Structure Affects How Ligands Bind 20 9
Amino Acid Sequences Can Also Be Deduced by Other
Oxygen Is Transported in Blood by Hemoglobin 21 0Methods 145
Hemoglobin Subunits Are Structurally Similar to Myoglobin 21 0Box 5-3 Investigating Proteins with Mass Spectrometry 146
Hemoglobin Undergoes a Structural Change on Bindin gAmino Acid Sequences Provide Important Biochemical
Oxygen 21 2Information 150
Hemoglobin Binds Oxygen Cooperatively 214Small Peptides and Proteins Can Be Chemically Synthesized 150
Cooperative Ligand Binding Can Be Described Quantitatively 21 5
Summary 152
Further Reading 153
Two Models Suggest Mechanisms for Cooperative Binding 21 5
Problems 154
Hemoglobin Also Transports H ' and C0 2 216Oxygen Binding to Hemoglobin Is Regulated by
2,3-Bisphosphoglycerate 21 86 The Three-Dimensional Structure of Proteins 159
Sickle-Cell Anemia Is a Molecular Disease of Hemoglobin 21 9Overview of Protein Structure 159
A Protein's Conformation Is Stabilized Largely by Weak
Complementary Interactions between Proteins and Ligands :The Immune System and Immunoglobulins 22 1
Interactions 160
The Immune Response Features a Specialized Array of Cells andThe Peptide Bond Is Rigid and Planar 161
Proteins 22 2
Protein Secondary Structure 163
Self Is Distinguished from Nonself by the Display of Peptides o nThe a Helix Is a Common Protein Secondary Structure 163
Cell Surfaces 223
• Box 6-1 Knowing the Right Hand from the Left 165 Molecular Interactions at Cell Surfaces Trigger the Immun e
Amino Acid Sequence Affects a Helix Stability 165
Response 22 5
The ß Conformation Organizes Polypeptide Chains into
Antibodies Have Two Identical Antigen Binding Sites 228
Sheets 166
ß Turns Are Common in Proteins 16 8
Common Secondary Structures Have Characteristic Bond Anglesand Amino Acid Content 16 9
Protein Tertiary and Quaternary Structures 170
Aa. 'IfFibrous Proteins Are Adapted for a Structural Function 170
%AO! }
• Box 6-2 Permanent Waving Is Biochemical Engineering 172 ,Structural Diversity Reflects Functional Diversity in Globula r
Proteins 175
Myoglobin Provided Early Clues about the Complexity of GlobularProtein Structure 17 5
• Box 6-3 Methods for Determining the Three-Dimensiona lStructure of a Protein 178
Globular Proteins Have a Variety of Tertiary Structures 18 2
Analysis of Many Globular Proteins Reveals Common Structural
page 20 9
Patterns 183
Antibodies Bind Tightly and Specifically to Antigen 230
• Box 8-2 Kinetic Tests for Determining InhibitionThe Antibody-Antigen Interaction Is the Basis for a Variety of
Mechanisms 26 7Important Analytical Procedures 231
Irreversible Inhibition Is an Important Tool in Enzyme Researc hand Pharmacology 26 8
Protein Interactions Modulated by Chemical Energy : Actin,
Enzyme Activity Is Affected by pH 26 9Myosin, and Molecular Motors 23 3The Major Proteins of Muscle Are Myosin and Actin 233
Examples of Enzymatic Reactions 26 9Additional Proteins Organize the Thin and Thick Filaments into
x Box 8-3 Evidence for Enzyme-Transition StateOrdered Structures 235
Complementarity 27 0Myosin Thick Filaments Slide along Actin Thin Filaments 237
Reaction Mechanisms Illustrate Principles 27 2
Summary 238
Further Reading 239
Regulatory Enzymes 278Problems 240
Allosteric Enzymes Undergo Conformational Changes in Respons eto Modulator Binding 27 8
8 Enzymes 243
The Regulatory Step in Many Pathways Is Catalyzed by a nAn Introduction to Enzymes 244
Allosteric Enzyme 28 0Most Enzymes Are Proteins 244
The Kinetic Properties of Allosteric Enzymes Diverge fro mEnzymes Are Classified by the Reactions They Catalyze 246
Michaelis Menten Behavior 280Some Regulatory Enzymes Undergo Reversible Covalen t
How Enzymes Work 246
Modification 28 1Enzymes Affect Reaction Rates, Not Equilibria 247
Phosphoryl Groups Affect the Structure and Catalytic Activity ofReaction Rates and Equilibria Have Precise Thermodynamic
Proteins 28 2Definitions 249
Multiple Phosphorylations Allow Exquisite Regulator yA Few Principles Explain the Catalytic Power and Specificity of
Control 28 4Enzymes 250
Some Types of Regulation Require Proteolytic Cleavage of a nWeak Interactions between Enzyme and Substrate Are Optimized
Enzyme Precursor 28 6in the Transition State 251
Some Regulatory Enzymes Use Multiple Regulator yBinding Energy Contributes to Reaction Specificity and
Mechanisms 28 7Catalysis 253
Summary 288
Further Reading 289Specific Catalytic Groups Contribute to Catalysis 255
Problems 29 0Enzyme Kinetics As an Approach to Understanding
Mechanism 257
9 Carbohydrates and Glycobiology 29 3Substrate Concentration Affects the Rate of Enzyme-Catalyzed
Monosaccharides and Disaccharides 294Reactions 257
The Two Families of Monosaccharides Are Aldoses an dThe Relationship between Substrate Concentration and Reaction
Ketoses 294Rate Can Be Expressed Quantitatively 259
Monosaccharides Have Asymmetric Centers 29 5n Box 8-1 Transformations of the Michaelis-Menten Equation : The
The Common Monosaccharides Have Cyclic Structures 297Double-Reciprocal Plot 26 1Kinetic Parameters Are Used to Compare Enzyme Activities 261
Organisms Contain a Variety of Hexose Derivatives 299
Many Enzymes Catalyze Reactions with Two or More
Monosaccharides Are Reducing Agents 30 1
Substrates 264
Disaccharides Contain a Glycosidic Bond 30 1
Pre-Steady State Kinetics Can Provide Evidence for Specific
Polysaccharides 30 3Reaction Steps 265
Starch and Glycogen Are Stored Fuels 30 4Enzymes Are Subject to Inhibition 265
Cellulose and Chitin Are Structural Homopolysaccharides 30 6Reversible Inhibition Can Be Competitive, Uncompetitive, or
Bacterial Cell Walls Contain Peptidoglycans 307Mixed 266
Glycosaminoglycans Are Components of the Extracellula rMatrix 308
Glycoconjugates: Proteoglycans, Glycoproteins, an dGlycolipids 31 1
lb"
Proteoglycans Are Glycosaminoglycan-Containing Macromolecule s•,~
of the Cell Surface and Extracellular Matrix 31 1f r
,06 ,~: .
'
Glycoproteins Are Information-Rich Conjugates Containing
~
Oligosaccharides 31 3~Glycolipids and Lipopolysaccharides Are Membran e
WIP , n,
Components 31 4I
Oligosaccharide-Lectin Interactions Mediate Many Biologica lProcesses 31 5
`4 Analysis of Carbohydrates 31 8k
Summary 320
Further Reading 32 1page 233
Problems 322
10 Nucleotides and Nucleic Acids 325 • •Some Basics 325
•
0O••
~•
i ••••-0 0
Nucleotides and Nucleic Acids Have Characteristic Bases and
•
Y
•
•i •
•• !•Pentoses 325
•
•00
Phosphodiester Bonds Link Successive Nucleotides in Nucleic
• •!~•!~ •!~ •!! 00400! •!N,•!! •!!!
00-
Acids 329
•i! •i!i •i!i •e!i •* •i!i • !i .iii •i!iThe Properties of Nucleotide Bases Affect the Three-Dimensional
S •ö!•0: 4 • 1 . • • i •g i •~~• •~~~ •iiiStructure of Nucleic Acids 331
+
• +~•
•4)
••
:
•
Nucleic Acid Structure 332
• •
•••e ••
• 5
••DNA Stores Genetic Information 333
••
•~••
••`•DNA Molecules Have Distinctive Base Compositions 334
page 41 1DNA Is a Double Helix 33 5DNA Can Occur in Different Three-Dimensional Forms 33 7Certain DNA Sequences Adopt Unusual Structures 33 9Messenger RNAs Code for Polypeptide Chains 341
Vitamins E and K and the Lipid Quinones Are Oxidation-Reductio nMany RNAs Have More Complex Three-Dimensional
Cofactors 38 2Structures 342
Dolichols Activate Sugar Precursors for Biosynthesis 38 2Nucleic Acid Chemistry 345
Separation and Analysis of Lipids 38 3Double-Helical DNA and RNA Can Be Denatured 34 5Nucleic Acids from Different Species Can Form Hybrids 347
Lipid Extraction Requires Organic Solvents 38 4Adsorption Chromatography Separates Lipids of Differen t
Nucleotides and Nucleic Acids Undergo Nonenzymatic
Polarity 384Transformations 348
Gas-Liquid Chromatography Resolves Mixtures of Volatile Lipi dSome Bases of DNA Are Methylated 351
Derivatives 385The Sequences of Long DNA Strands Can Be Determined 351
Specific Hydrolysis Aids in Determination of Lipid Structure 385The Chemical Synthesis of DNA Has Been Automated 354
Mass Spectrometry Reveals Complete Lipid Structure 386Other Functions of Nucleotides 354
Summary 386
Further Reading 387Nucleotides Carry Chemical Energy in Cells 354
Problems 388Adenine Nucleotides Are Components of Many Enzyme
Cofactors 356
12 Biological Membranes and Transport 38 9Some Nucleotides Are Regulatory Molecules 358
The Molecular Constituents of Membranes 39 0Summary 359
Further Reading 360
Each Type of Membrane Has Characteristic Lipids an dProblems 361
Proteins 39 0
11 Lipids 363
The Supramolecular Architecture of Membranes 39 1A Lipid Bilayer Is the Basic Structural Element o f
Storage Lipids 363
Membranes 39 2Fatty Acids Are Hydrocarbon Derivatives 363
Membrane Lipids Are in Constant Motion 394Triacylglycerols Are Fatty Acid Esters of Glycerol 366
Membrane Proteins Diffuse Laterally in the Bilayer 39 5Triacylglycerols Provide Stored Energy and Insulation 366
n Box 12-1 Looking at Membranes 396n Box 11-1 Sperm Whales: Fatheads of the Deep 367
Some Membrane Proteins Span the Lipid Bilayer 396Many Foods Contain Triacylglycerols 368
Peripheral Membrane Proteins Are Easily Solubilized 39 8Waxes Serve as Energy Stores and Water Repellents 368
Covalently Attached Lipids Anchor Some Peripheral Membran eStructural Lipids in Membranes 369
Proteins 40 0
Glycerophospholipids Are Derivatives of Phosphatidic Acid 369
Integral Proteins Are Held in the Membrane by Hydrophobi cInteractions with Lipids 400
Some Phospholipids Have Ether Linked Fatty Acids 371
The Topology of an Integral Membrane Protein Can Sometimes B eSphingolipids Are Derivatives of Sphingosine 372
Predicted from Its Sequence 40 2Sphingolipids at Cell Surfaces Are Sites of Biological
Integral Proteins Mediate Cell-Cell Interactions an dRecognition 373
Adhesion 40 4Phospholipids and Sphingolipids Are Degraded in Lysosomes 374
Membrane Fusion Is Central to Many Biological Processes 40 5n Box 11-2 Inherited Human Diseases Resulting from Abnorma l
Accumulations of Membrane Lipids 375
Solute Transport across Membranes 408Sterols Have Four Fused Carbon Rings 376
Passive Transport Is Facilitated by Membrane Proteins 40 8Aquaporins Form Hydrophilic Transmembrane Channels for th e
Lipids as Signals, Cofactors, and Pigments 376
Passage of Water 41 0Phosphatidylinositols Act as Intracellular Signals 377
The Glucose Transporter of Erythrocytes Mediates Passiv eEicosanoids Carry Messages to Nearby Cells 378
Transport 41 1Steroid Hormones Carry Messages between Tissues 379
Chloride and Bicarbonate Are Cotransported across the Erythrocyt eVitamins A and D Are Hormone Precursors 380
Membrane 413
The ß-Adrenergic Receptor Is Desensitized byQ
S
Phosphorylation 45 4
+
Cyclic AMP Acts as a Second Messenger for a Number o f10
•
Regulatory Molecules 45 4v-';=--
Two Second Messengers Are Derived fro m
0•"C I•ml
s‘ iL ,
t .3 wA
riot
Phosphatidylinositols 45 6
~i . mort fowl
y*la ;
~rt
Calcium Is a Second Messenger in Many Signa laril owl ti n 9 iI mpg Ion ion ! w
it slit
. Transductions 45 711'n
Oki 03r! 111r_ ,
laz*„Sensory Transduction in Vision, Olfaction, and Gustation 45 8
VI)
Light Hyperpolarizes Rod and Cone Cells of the Vertebrat eI_
Eye 458
page 418
Light Triggers Conformational Changes in the Recepto rRhodopsin 46 0
Excited Rhodopsin Acts through the G Protein Transducin t oReduce the cGMP Concentration 46 0
n Box 12-2 Defective Glucose and Water Transport in Two Forms
Signal Amplification Occurs in Rod and Cone Cells 46 0
of Diabetes 414
The Visual Signal Is Terminated Quickly 46 1
Active Transport Results in Solute Movement against a
Rhodopsin Is Desensitized by Phosphorylation 46 2
Concentration or Electrochemical Gradient 415
Cone Cells Specialize in Color Vision 46 2
There Are at Least Four General Types of Transport ATPases 416
n Box 13-2 Color Blindness: John Dalton's Experiment from
n Box 12-3 A Defective /on Channel Causes Cystic Fibrosis 418
the Grave 463
A P-Type ATPase Catalyzes Active Cotransport of Na'
Vertebrate Olfaction and Gustation Use Mechanisms Similar to th e
and K` 420
Visual System 46 3
ATP-Driven Ca' Pumps Maintain a Low Concentration of Calcium
G Protein-Coupled Serpentine Receptor Systems Share Severa l
in the Cytosol 421
Features 465
Ion Gradients Provide the Energy for Secondary Active
Disruption of G-Protein Signaling Causes Disease 46 6
Transport 422
Phosphorylation as a Regulatory Mechanism 467Ion Selective Channels Allow Rapid Movement of Ions across
Localization of Protein Kinases and Phosphatases Affects th eMembranes 424
Specificity for Target Proteins 46 7The Structure of a K ' Channel Shows the Basis for Its Io n
Specificity 424
Regulation of Transcription by Steroid Hormones 46 8
The Acetylcholine Receptor Is a Ligand-Gated Ion Channel 426
Regulation of the Cell Cycle by Protein Kinases 469The Neuronal Na' Channel Is a Voltage-Gated Ion Channel 428
The Cell Cycle Has Four Stages 46 9Ion-Channel Function Is Measured Electrically 429
Levels of Cyclin-Dependent Protein Kinases Oscillate 469Defective Ion Channels Can Have Striking Physiological
CDKs Regulate Cell Division by Phosphorylating Critica lConsequences 430
Proteins 47 3Porins Are Transmembrane Channels for Small Molecules 430
Oncogenes, Tumor Suppressor Genes, and Programmed Cel l
Summary 432
Further Reading 433
Death 474Problems 434
Oncogenes Are Mutant Forms of the Genes for Proteins tha tRegulate the Cell Cycle 47 4
13 Biosignaling 437
Defects in Tumor Suppressor Genes Remove Normal Restraints o n
Molecular Mechanisms of Signal Transduction 437
Cell Division 47 5
n Box 13-1 Scatchard Analysis Quantifies the Receptor-Ligand
Apoptosis Is Programmed Cell Suicide 476
Interaction 439
Summary 478
Further Reading 479
Gated Ion Channels 441
Problems 481
Ion Channels Underlie Electrical Signaling in Excitable Cells 44 1
The Nicotinic Acetylcholine Receptor Is a Ligand-Gated Ion
III Bioenergetics and Metabolism 485Channel 44 3
Voltage-Gated Ion Channels Produce Neuronal Action
14 Principles of Bioenergetics 490Potentials 444
Neurons Have Receptor Channels That Respond to a Variety of
Bioenergetics and Thermodynamics 491
Neurotransmitters 445
Biological Energy Transformations Obey the Laws ofThermodynamics 49 1
Receptor Enzymes 445
n Box 14-1 Entropy: The Advantages of Being Disorganized 492The Insulin Receptor Is a Tyrosine-Specific Protein Kinase 445
Cells Require Sources of Free Energy 49 3Guanylyl Cyclase Is a Receptor Enzyme That Generates the Second
The Standard Free-Energy Change Is Directly Related to th eMessenger cGMP 448
Equilibrium Constant 494G Protein-Coupled Receptors and Second Messengers 449
Actual Free-Energy Changes Depend on Reactant and Product
The ß-Adrenergic Receptor System Acts through the Second
Concentrations 49 6Messenger cAMP 449
Standard Free-Energy Changes Are Additive 498
Phosphoryl Group Transfers and ATP 499
Other Monosaccharides Enter the Glycolytic Pathway at Severa lThe Free-Energy Change for ATP Hydrolysis Is Large
Points 549and Negative 500
Dietary Polysaccharides and Disaccharides Are Hydrolyzed t on Box 14-2 The Free Energy of Hydrolysis of ATP within Cells: The
Monosaccharides 550
Real Cost of Doing Metabolic Business 501
Regulation of Carbohydrate Catabolism 55 1Other Phosphorylated Compounds and Thioesters Also Have Large
Regulatory Enzymes Act as Metabolic Valves 55 1Free Energies of Hydrolysis 502
Glycolysis and Gluconeogenesis Are Coordinately Regulated 553ATP Provides Energy by Group Transfers, Not by Simpl eHydrolysis 504
Phosphofructokinase-1 Is under Complex Allosteri cRegulation 554
ATP Donates Phosphoryl, Pyrophosphoryl, and Adenyly lGroups 506
Hexokinase Is Allosterically Inhibited by Its Reaction Product 555
Assembly of Informational Macromolecules Requires Energy 508
NI Box 15-3 Isozymes: Different Proteins, Same Reaction 556
ATP Energizes Active Transport and Muscle Contraction 508
Pyruvate Kinase Is Inhibited by ATP 556
• Box 14-3 Firefly Flashes: Glowing Reports of ATP 509
Glycogen Phosphorylase Is Regulated Allostericall y
Transphosphorylations between Nucleotides Occurand Hormonally 55 7
in All Cell Types 510
The Pentose Phosphate Pathway of Glucose Oxidation 55 8Inorganic Polyphosphate Is a Potential Phosphoryl
n Box 15-4 Glucose 6-Phosphate Dehydrogenase Deficiency:Group Donor 511
Why Pythagoras Wouldn't Eat Falafel 560
Biochemical and Chemical Equations Are Not Identical 511
Summary 561
Further Reading 56 2Biological Oxidation-Reduction Reactions 512
Problems 56 3The Flow of Electrons Can Do Biological Work 512
Oxidation-Reductions Can Be Described as Half-Reactions 513
16 The Citric Acid Cycle 56 7
Biological Oxidations Often Involve Dehydrogenation 514
Production of Acetate 568
Reduction Potentials Measure Affinity for Electrons 515
Pyruvate Is Oxidized to Acetyl-CoA and CO 2 568
Standard Reduction Potentials Can Be Used to Calculate the
The Pyruvate Dehydrogenase Complex Requires FiveFree-Energy Change 516
Coenzymes 569
Cellular Oxidation of Glucose to Carbon Dioxide Requires
The Pyruvate Dehydrogenase Complex Consists of Three Distinc tSpecialized Electron Carriers 517
Enzymes 570
A Few Types of Coenzymes and Proteins Serve as Universal
Intermediates Remain Bound to the Enzyme Surface 57 0
Electron Carriers 518
Reactions of the Citric Acid Cycle 57 1NADH and NADPH Act with Dehydrogenases as Soluble Electron
The Citric Acid Cycle Has Eight Steps 573Carriers 518 Box
Flavin Nucleotides Are Tightly Bound in Flavoproteins 520
•
16-1 Synthases and Synthetases ; Ligases and Lyases ;Kinases, Phosphatases, and Phosphorylases : Yes, the Names
Summary 522
Further Reading 523
Are Confusing! 576
Problems 524
The Energy of Oxidations in the Cycle Is EfficientlyConserved 579
15 Glycolysis and the Catabolism of Hexoses 527
n Box 16-2 Citrate: A Symmetrical Molecule That Reacts
Glycolysis 527
Asymmetrically 580
An Overview : Glycolysis Has Two Phases 528
Why Is the Oxidation of Acetate So Complicated? 58 1
The Preparatory Phase of Glycolysis Requires ATP 532
Citric Acid Cycle Components Are Important Biosyntheti c
The Payoff Phase of Glycolysis Produces ATP and NADH 535
Intermediates 583
•Overall Balance Sheet Shows a Net Gain of ATP 540
Box 16-3 Citrate Synthase, Soda Pop, and the Worl dThe Food Supply 583Intermediates Are Channeled between Glycolytic Enzymes 540
Anaplerotic Reactions Replenish Citric Acid Cycl eGlycolysis Is under Tight Regulation 541
Intermediates 584Glucose Catabolism Is Deranged in Cancerous Tissue 54 1
Fates of Pyruvate under Aerobic and AnaerobicConditions 542
Pyruvate Is the Terminal Electron Acceptor in Lactic Aci dFermentation 542
n Box 15-1 Glycolysis at Limiting Concentrations of Oxygen:Athletes, Alligators, and Coelacanths 543
n Box 15-2 Brewing Beer 544
'e:.
Ethanol Is the Reduced Product in Alcohol Fermentation 544
'`
$ +Thiamine Pyrophosphate Carries "Active Aldehyde" Groups 545
11 . 1Microbial Fermentations Yield Other End Products of Commercia l
Value 546,er
4 >
Feeder Pathways for Glycolysis 54 7Glycogen and Starch Are Degraded by Phosphorolysis 547
page 509
~''
Biotin in Pyruvate Carboxylase Carries CO 2 Groups 585
Extrahepatic Tissues Use Ketone Bodies as Fuels 61 7
Regulation of the Citric Acid Cycle 586
Ketone Bodies Are Overproduced in Diabetes and durin g
Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex
Starvation 61 7
Is Regulated by Allosteric and Covalent Mechanisms 586
Summary 618
Further Reading 61 9The Citric Acid Cycle Is Regulated at Its Three Exergonic
Problems 62 0Steps 58 7
The Glyoxylate Cycle 588
18 Amino Acid Oxidation and the Productio nThe Glyoxylate Cycle Produces Four-Carbon Compounds
of Urea 623from Acetate 589
Metabolic Fates of Amino Groups 62 4
The Citric Acid and Glyoxylate Cycles Are Coordinately
Dietary Protein Is Enzymatically Degraded to Amino Acids 62 6Regulated 590
Pyridoxal Phosphate Participates in the Transfer of a-Amin oGroups to a-Ketoglutarate 62 8
Summary 592
Further Reading 592Problems 594
n Box 18-1 Assays for Tissue Damage 63 1
Glutamate Releases Ammonia in the Liver 63 1
17 Oxidation of Fatty Acids 598
Glutamine Transports Ammonia in the Bloodstream 63 2
Digestion, Mobilization, and Transport of Fats 599
Alanine Transports Ammonia from Muscles to the Liver 63 2
Dietary Fats Are Absorbed in the Small Intestine 599
Ammonia Is Toxic to Animals 63 3
Hormones Trigger Mobilization of Stored Triacylglycerols 601
Nitrogen Excretion and the Urea Cycle 63 4
Fatty Acids Are Activated and Transported into
Urea Is Produced from Ammonia in Five Enzymatic Steps 63 5Mitochondria 602
The Citric Acid and Urea Cycles Can Be Linked 63 6
ß Oxidation 604
The Activity of the Urea Cycle Is Regulated at Two Levels 63 6
The ß Oxidation of Saturated Fatty Acids Has Four Basic
Pathway Interconnections Reduce the Energetic Cost of Urea
Steps 604
Synthesis 63 7
The Four Steps Are Repeated to Yield Acetyl-CoA and ATP 605
Genetic Defects in the Urea Cycle Can Be Life-Threatening 63 7
n Box 17-1 Fat Bears Carry Out ß Oxidation in Their Sleep 606
Natural Habitat Determines the Pathway for Nitroge n
Acetyl-CoA Can Be Further Oxidized in the Citric
Excretion 638
Acid Cycle 607
Pathways of Amino Acid Degradation 63 9
Oxidation of Unsaturated Fatty Acids Requires Two Additional
Several Enzyme Cofactors Play Important Roles in Amino Aci dReactions 607
Catabolism 640Complete Oxidation of Odd-Number Fatty Acids Requires Three
Ten Amino Acids Are Degraded to Acetyl-CoA 64 3Extra Reactions 608
Phenylalanine Catabolism Is Genetically Defective in Som en Box 17-2 Coenzyme 8 12 : A Radical Solution to a Perplexing
People 64 6Problem 610
Five Amino Acids Are Converted to a-Ketoglutarate 64 8Fatty Acid Oxidation Is Tightly Regulated 612
Four Amino Acids Are Converted to Succinyl-CoA 65 0Peroxisomes Also Carry Out ß Oxidation 612
Branched-Chain Amino Acids Are Not Degraded in the Liver 65 1Plant Peroxisomes and Glyoxysomes Use Acetyl-CoA from
n Box 18-2 Scientific Sleuths Solve a Murder Mystery 654ß Oxidation as a Biosynthetic Precursor 613
Asparagine and Aspartate Are Degraded to Oxaloacetate 653The ß-Oxidation Enzymes of Different Organelles Have Diverged
Some Amino Acids Can Be Converted to Glucose, Others to Keton eduring Evolution 614
Bodies 654Omega Oxidation Occurs in the Endoplasmic Reticulum 61 4
Genetic Defects in Fatty Acyl-CoA Dehydrogenases Cause Serious
Summary 654
Further Reading 655
Disease 615
Problems 65 6
Ketone Bodies 61 5
Ketone Bodies Formed in the Liver Are Exported to Other
19 Oxidative Phosphorylation an dOrgans 616
Photophosphorylation 65 9Oxidative Phosphorylation 66 0
Electon-Transfer Reactions in Mitochondria 66 0
,., .. "
Electrons Are Funneled to Universal Electron Acceptors 66 1
Electons Pass through a Series of Membrane-Bound Carriers 66 2
Electron Carriers Function in Multienzyme Complexes 66 6
44101
The Energy of Electron Transfer Is Efficiently Conserved in aProton Gradient 67 2ja:
9
6
Plant Mitochondria Have Alternative Mechanisms for Oxidizin g
w
NADH 673
n Box 19-1 Alternative Respiratory Pathways and Hot, Stinking
Plants 674
ATP Synthesis 67 5page 629
ATP Synthase Has Two Functional Domains, F e and F 1 678~jy
ATP Is Stabilized Relative to ADP on the Surface of F 1 678
ly
1r
r
p
The Proton Gradient Drives the Release of ATP from the Enzyme
r=
~ . .
Surface 679
, .
;
. .'
A i .Each ß Subunit of ATP Synthase Can Assume Three Different
;,
%
Conformations 680
f_
f
w ;
.1-Rotational Catalysis Is Key to the Binding-Change Mechanism for
: `=ter.
•. rATP Synthesis 682
v
'Chemiosmotic Coupling Allows Nonintegral Stoichiometries of 0 2
~ 'Consumption and ATP Synthesis 683
±~ =N C
'`The Proton-Motive Force Energizes Active Transport 68 4
Shuttle Systems Are Required for Mitochondrial Oxidation of
page 68 1Cytosolic NADH 68 5
Regulation of Oxidative Phosphorylation 68 6
Oxidative Phosphorylation Is Regulated by Cellula rEnergy Needs 68 7
Uncoupled Mitochondria in Brown Fat Produce Heat 687
20 Carbohydrate Biosynthesis 722ATP-Producing Pathways Are Coordinately Regulated 688
Gluconeogenesis 723Mutations in Mitochondria) Genes Cause Human Disease 688
Conversion of Pyruvate to Phosphoenolpyruvate Requires Tw oMitochondria Probably Evolved from Endosymbiotic Bacteria 690
Exergonic Reactions 72 6
Photosynthesis : Harvesting Light Energy 691
Conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphat eIs the Second Bypass 72 8
General Features of Photophosphorylation 691
Conversion of Glucose 6-Phosphate to Free Glucose Is the Thir dPhotosynthesis in Plants Takes Place in Chloroplasts 692
Bypass 72 8Light Drives Electron Flow in Chloroplasts 692
Gluconeogenesis is Expensive 72 9
Light Absorption 693
Citric Acid Cycle Intermediates and Many Amino Acids Are
Chlorophylls Absorb Light Energy for Photosynthesis 693
Glucogenic 73 0
Accessory Pigments Extend the Range of Light Absorption 696
Futile Cycles in Carbohydrate Metabolism Consume ATP 73 0
Chlorophyll Funnels Absorbed Energy to Reaction Centers by
Gluconeogenesis and Glycolysis Are Reciprocally Regulated 73 1
Exciton Transfer 697
Gluconeogenesis Converts Fats and Proteins to Glucose i nGerminating Seeds 73 3
The Central Photochemical Event : Light-DrivenElectron Flow 699
Biosynthesis of Glycogen, Starch, Sucrose, and Othe r
Bacteria Have One of Two Types of Single Photochemical Reaction
Carbohydrates 735
LCenters 699
UDP-Glucose Is the Substrate for Glycogen Synthesis 73 6
Kinetic and Thermodynamic Factors Prevent Energy Dissipation by
Glycogen Synthase and Glycogen Phosphorylase Are Reciprocall y
Internal Conversion 702
Regulated 73 8
In Higher Plants, Two Reaction Centers Act in Tandem 702
ADP-Glucose Is the Substrate for Starch Synthesis in Plants an d
Spatial Separation of Photosystems I and II Prevents Exciton
Glycogen Synthesis in Bacteria 73 9
Larceny 705
UDP-Glucose Is the Substrate for Sucrose Synthesi s
The Cytochrome b6 f Complex Links Photosystems II and I 706
in Plants 74 1
Cyanobacteria Use the Cytochrome b 6 f Complex and Cytochrome c6
Lactose Synthesis Is Regulated in a Unique Way 74 2
in Both Oxidative Phosphorylation and
UDP-Glucose is an intermediate in the Formation of Glucuronat ePhotophosphorylation 706
and Vitamin C 74 3
Water Is Split by the Oxygen-Evolving Complex 707
Sugar Nucleotides Are Precursors in Bacterial Cell Wal lSynthesis 74 4
ATP Synthesis by Photophosphorylation 708
n Box 20-1 Penicillin and d-Lactamase : The Magic Bullet versu sA Proton Gradient Couples Electron Flow and Phosphorylation 708
the Bulletproof Vest 746The Approximate Stoichiometry of Photophosphorylation Has Bee n
Established 709
Photosynthetic Carbohydrate Synthesis 746
Cyclic Electron Flow Produces ATP but Not NADPH or 0 2 710
Carbon Dioxide Assimilation Occurs in Three Stages 74 8
The ATP Synthase of Chloroplasts Is Like That of
Each Triose Phosphate Synthesized from CO 2 Costs Six NADP H
Mitochondria 710
and Nine ATP 75 4
Chloroplasts Probably Evolved from Endosymbiotic
A Transport System Exports Triose Phosphates from the Chloroplas t
Cyanobacteria 711
and Imports Phosphate 75 5
Diverse Photosynthetic Organisms Use Hydrogen Donors Other
Regulation of Carbohydrate Metabolism in Plants 75 7Than Water 711
Rubisco Is Subject to Both Positive and Negative Regulation 75 7In Halophilic Bacteria, a Single Protein Absorbs Light and Pumps
Certain Enzymes of the Calvin Cycle Are Indirectly Activate dProtons to Drive ATP Synthesis 712
by Light 758
Summary 714
Further Reading 715
The Use of Triose Phosphates for Sucrose and Starch Synthesis Is
i 1Problems 718
Tightly Regulated in Plants 759
Plasmalogen Synthesis Requires Formation of an Ether-Linkedd
~.
'',I
Fatty Alcohol 79 6V. 1 ,
,,'
,
Sphingolipid and Glycerophospholipid Synthesis Share Precursor s,
1st)
'
and Some Mechanisms 798
,/' ,
Polar Lipids Are Targeted to Specific Cell Membranes 79 8
y .. .
' a",
Biosynthesis of Cholesterol, Steroids, and Isoprenoids 799,),„
-J>
,
Cholesterol Is Made from Acetyl-CoA in Four Stages 79 9*,'~iE
F
r
_
s ,' •'
Cholesterol Has Several Fates 804
Cholesterol and Other Lipids Are Carried on Plasm aLipoproteins 804
• Box 21-3 Apolipoprotein E Alleles Predict Incidence ofpage 805
Alzheimer's Disease 808
Cholesteryl Esters Enter Cells by Receptor-Mediate dEndocytosis 80 9
Cholesterol Biosynthesis Is Regulated by Several Factors 81 0
Photorespiration Results from Rubisco's Oxygenase Activity 760
Steroid Hormones Are Formed by Side Chain Cleavage an d
Some Plants Have a Mechanism to Minimize Photorespiration 761
Oxidation of Cholesterol 81 2
Summary 763
Further Reading 765
Intermediates in Cholesterol Biosynthesis Have Many Alternativ e
Problems 766
Fates 81 2
Summary 814
Further Reading 81521 Lipid Biosynthesis 770
Problems 816
Biosynthesis of Fatty Acids and Eicosanoids 770
22 Biosynthesis of Amino Acids, Nucleotides, an dMalonyl-CoA Is Formed from Acetyl-CoA and Bicarbonate 770
Related Molecules 81 8Fatty Acids Are Synthesized by a Repeating Reaction
Sequence 772
Overview of Nitrogen Metabolism 81 9
The Fatty Acid Synthase Complex Has Seven Different
The Nitrogen Cycle Maintains a Pool of Biologically Availabl e
Active Sites 772
Nitrogen 81 9
Fatty Acid Synthase Receives the Acetyl and Malonyl Groups 774
Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex 82 0
The Fatty Acid Synthase Reactions Are Repeated to Form
Ammonia Is Incorporated into Biomolecules through Glutamat e
Palmitate 776
and Glutamine 823
The Fatty Acid Synthase of Some Organisms Is Composed of
Glutamine Synthetase Is a Primary Regulatory Point in Nitroge n
Multifunctional Proteins 777
Metabolism 824
Fatty Acid Synthesis Occurs in the Cytosol of Many Organisms but
Several Classes of Reactions Play Special Roles in th e
in the Chloroplasts of Plants 778
Biosynthesis of Amino Acids and Nucleotides 82 6
Acetate Is Shuttled out of Mitochondria as Citrate 779
Biosynthesis of Amino Acids 82 6Fatty Acid Biosynthesis Is Tightly Regulated 780
a-Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, an dLong-Chain Saturated Fatty Acids Are Synthesized from Palmitate
Arginine 829781
Serine, Glycine, and Cysteine Are Derived fro mSome Fatty Acids Are Desaturated 781
3-Phosphoglycerate 82 9
n
Box 21-1 Mixed-Function Oxidases, Oxygenases, and Three Nonessential and Six Essential Amino Acids Are Synthesized
Cytochrome P-450 782
from Oxaloacetate and Pyruvate 83 1
Eicosanoids Are Formed from 20-Carbon Polyunsaturated Fatty
Chorismate Is a Key Intermediate in the Synthesis of Tryptophan ,
Acids 784
Phenylalanine, and Tyrosine 83 4
n
Box 21-2 Cyclooxygenase lsozymes and the Search fora Better Histidine Biosynthesis Uses Precursors of Purin eAspirin : Relief is in (the Active) Site 786
Biosynthesis 83 9
Biosynthesis of Triacylglycerols 786
Amino Acid Biosynthesis Is under Allosteric Regulation 83 9
Triacylglycerols and Glycerophospholipids Are Synthesized from
Molecules Derived from Amino Acids 84 0the Same Precursors 788
Glycine Is a Precursor of Porphyrins 84 0Triacylglycerol Biosynthesis in Animals Is Regulated by
n Box 22-1 Biochemistry of Kings and Vampires 84 1Hormones 790
Degradation of Herne Yields Bile Pigments 84 2
Biosynthesis of Membrane Phospholipids 791
Amino Acids Are Required for the Biosynthesis of Creatine an d
There Are Two Strategies for Attaching Head Groups 791
Glutathione 842
Phospholipid Synthesis in E. coli Employs
a-Amino Acids Are Found Primarily in Bacteria 843
CDP-Diacylglycerol 792
Aromatic Amino Acids Are Precursors of Many Plan t
Eukaryotes Synthesize Anionic Phospholipids from CDP-
Substances 843
Diacylglycerol 794
Amino Acids Are Converted to Biological Amines b y
Eukaryotic Pathways to Phosphatidylserine,
Decarboxylation 84 4
Phosphatidylethanolamine, and Phosphatidylcholine Are
• Box 22-2 Curing African Sleeping Sickness with a Biochemica lInterrelated 794
Trojan Horse 846
Arginine Is the Precursor for Biological Synthesis of Nitric
IV Information Pathways
90 5Oxide 848
Biosynthesis and Degradation of Nucleotides 848
24 Genes and Chromosomes 907De Novo Purine Synthesis Begins with PRPP 849
Chromosomal Elements 90 8Purine Nucleotide Biosynthesis Is Regulated by Feedback
Genes Are Segments of DNA That Code for Polypeptide Chainsinhibition 852
and RNAs 908Pyrimidine Nucleotides Are Made from Aspartate, PRPP, and
Eukaryotic Chromosomes Are Very Complex 909Carbamoyl Phosphate 853
Many Eukaryotic Genes Contain Intervening Nontranscribe dPyrimidine Nucleotide Biosynthesis Is Regulated by Feedback
Sequences (Introns) 91 0Inhibition 85 5
Nucleoside Monophosphates Are Converted to Nucleoside
The Size and Sequence Structure of DNA Molecules 91 1
Triphosphates 855
Viral DNA Molecules Are Relatively Small 91 1
Ribonucleotides Are the Precursors of Deoxyribonucleotides 856
Bacteria Contain Chromosomes and Extrachromosomal DNA 91 2
Thymidylate Is Derived from dCDP and dUMP 860
Eukaryotic Cells Contain More DNA Than Do Prokaryotes 91 4
Degradation of Purines and Pyrimidines Produces Uric Acid and
Organelles of Eukaryotic Cells Also Contain DNA 91 5
Urea, Respectively 861
DNA Supercoiling 91 5Purine and Pyrimidine Bases Are Recycled by Salvage
Most Cellular DNA Is Underwound 91 7Pathways 86 2
Overproduction of Uric Acid Causes Gout 863
DNA Underwinding Is Defined by Topological Linkin gNumber 918
Many Chemotherapeutic Agents Target Enzymes in the Nucleotide
Topoisomerases Catalyze Changes in the Linking Numbe rBiosynthetic Pathways 863
of DNA 92 1Summary 865
Further Reading 866
DNA Compaction Requires a Special Form of Supercoiling 922Problems 867
Chromatin and Nucleoid Structure 92 3
23 Integration and Hormonal Regulation of
Histones Are Small, Basic Proteins 92 4
Mammalian Metabolism 869
Nucleosomes Are the Fundamental Organizational Units of
Tissue-Specific Metabolism : The Division of Labor 869
Chromatin 92 4
Nucleosomes Are Packed into Successively Higher-Orde rThe Liver Processes and Distributes Nutrients 870
Structures 92 6Adipose Tissue Stores and Supplies Fatty Acids 873
Bacterial DNA Is Also Highly Organized 92 7Muscle Uses ATP for Mechanical Work 874
The Brain Uses Energy for Transmission of Electrical
Summary 928
Further Reading 92 9
Impulses 876
Problems 930
Blood Carries Oxygen, Metabolites, and Hormones 877
25 DNA Metabolism 93 1Hormonal Regulation of Fuel Metabolism 878
A Word about Terminology 93 3Epinephrine Signals Impending Activity 87 8
Glucagon Signals Low Blood Glucose 879
DNA Replication 93 3
During Fasting and Starvation, Metabolism Shifts to Provide Fuel
DNA Replication Is Governed by a Set of Fundamenta lRules 933
for the Brain 880
Insulin Signals High Blood Glucose 882
DNA Is Degraded by Nucleases 93 6
Cortisol Signals Stress, Including Low Blood Glucose 882
DNA Is Synthesized by DNA Polymerases 936
!
Diabetes Is a Defect in Insulin Production or Action 883
Replication Is Very Accurate 938
E. col/ Has at Least Five DNA Polymerases 93 9Hormones: Diverse Structures for Diverse Functions 88 4
Hormone Discovery and Purification Requires a Bioassay 88 4
n Box 23-1 How is a Hormone Discovered? The Arduous Pathwayto Purified insulin 885
Hormones Act through Specific High-Affinity Cellula rReceptors 887
. :
Hormones Are Chemically Diverse 88 9
What Regulates the Regulators? 89 3
Long-Term Regulation of Body Mass 896
Leptin Was Predicted by the Lipostat Theory 896
Many Factors Regulate Feeding Behavior and Energ yExpenditure 898
Leptin Triggers a Regulatory Cascade 89 8
The Leptin System May Have Evolved to Regulate the Starvatio nResponse 89 9
Summary 900
Further Reading 90 1Problems 902
page 904
1
DNA Replication Requires Many Enzymes and
RNA Catalyzes Splicing 99 2Protein Factors 942
Eukaryotic mRNAs Undergo Additional Processing 99 7Replication of the E. coll Chromosome Proceeds in Stages 942
Multiple Products Are Derived from One Gene by Differential RN AReplication in Eukaryotic Cells Is More Complex 948
Processing 99 9
DNA Repair 949
Ribosomal RNAs and tRNAs Also Undergo Processing 1000
Mutations Are Linked to Cancer 949
Some Events in RNA Metabolism Are Catalyze d
All Cells Have Multiple DNA Repair Systems 950
by RNA Enzymes 1003
n Box 25-1 DNA Repair and Cancer 953
Cellular mRNAs Are Degraded at Different Rates 1005
The Interaction of Replication Forks with DNA Damage Leads to
Polynucleotide Phosphorylase Makes Random RNA-lik ePolymers 1006
Recombination or Error-Prone Repair 958
DNA Recombination 959
RNA-Dependent Synthesis of RNA and DNA 1007
Homologous Genetic Recombination Has Multiple Functions 960Reverse Transcriptase Produces DNA from Viral RNA 100 7
Recombination during Meiosis Is Initiated with Double-Strand
Retroviruses Cause Cancer and AIDS 100 9
Breaks 962
n Box 26-2 FightingA/DS with Inhibitors of H/V Reverse
Recombination Requires Specific Enzymes 963
Transcriptase 101 0
TAll Aspects of DNA Metabolism Come Together to Repair Stalled
Evolutionaryosons ,
Origi nRetrov i
101 0ruses, and Introns May Have a Commo n
Replication Forks 967Telomerase Is a Specialized Reverse Transcriptase 1012
Site-Specific Recombination Results in Precise DN ARearrangements 967
Some Viral RNAs Are Replicated by RNA-Directed RN A
Complete Chromosome Replication Can Require Site-Specific
Polymerase 101 3
Recombination 970
RNA Synthesis Offers Important Clues to Biochemica l
Transposable Genetic Elements Move from One LocationEvolution 101 4
to Another 970
Summary 1017
Further Reading 101 7Immunoglobulin Genes Are Assembled by Recombination 973
Problems 1019
Summary 975
Further Reading 976
27 Protein Metabolism 1020Problems 977
The Genetic Code 1020
26 RNA Metabolism 979
The Genetic Code Was Cracked Using Artificial mRN ATemplates 1022
DNA-Dependent Synthesis of RNA 980
n Box 27-1 Translational Frameshifting and RNA Editing : mRNAsRNA Is Synthesized by RNA Polymerases 980
That Change Horses in Midstream 1026RNA Synthesis Is Initiated at Promoters 983
Wobble Allows Some tRNAs to Recognize More tha nTranscription Is Regulated 984
One Codon 102 8n Box 26-1 RNA Polymerase Leaves Its Footprint on a
n Box 27-2 Natural Variations in the Genetic Code 1030Promoter 985
Overlapping Genes in Different Reading Frames Are Found i nSpecific Sequences Signal Termination of RNA Synthesis 986
Some Viral DNAs 1032Eukaryotic Cells Have Three Kinds of Nuclear RNA
Polymerases 986
Protein Synthesis 1034
RNA Polymerase II Requires Many Other Proteins for Its
The Ribosome Is a Complex Supramolecular Machine 1035
Activity 987
Transfer RNAs Have Characteristic Structural Features 1037
DNA-Dependent RNA Polymerase Can Be Selectively
Stage 1 : Aminoacyl-tRNA Synthetases Attach the Correct Amin oInhibited 990
Acids to Their tRNAs 1039
RNA Processing 990
Stage 2 : A Specific Amino Acid Initiates Protein Synthesis 1044
The Introns Transcribed into RNA Are Removed by Splicing 991
Stage 3 : Peptide Bonds Are Formed in the Elongation Stage 104 7Stage 4 : Termination of Polypeptide Synthesis Requires a Specia l
Signal 1050n Box 27-3 Induced Variation in the Genetic Code: Nonsense
Suppression 105 1§,~
Stage 5 : Newly Suppressed Polypeptide Chains Undergo Foldin gand Processing 1053
.' .'
kTl ,
Itir
'
Protein Synthesis Is Inhibited by Many Antibiotics an dA • ce
► ,
4
Toxins 1054i . : 11 1
r~~!►. T
4
Protein Targeting and Degradation 1056..:.r
IR
>
Posttranslational Modification of Many Eukaryotic Proteins Begin s')
b%
AA
F
in the Endoplasmic Reticulum 1057lwo'vi
Glycosylation Plays a Key Role in Protein Targeting 1058Ir
S ;
Proteins Are Targeted to Mitochondria and Chloroplasts by Simila rPathways 106 1
page 1043
Signal Sequences for Nuclear Transport Are Not Cleaved 1063
Bacteria Also Use Signal Sequences for Protein Targeting 106 4Cells Import Proteins by Receptor-Mediated Endocytosis 1065
_
.iw
ia.
Protein Degradation Is Mediated by Specialized Systems in All
.viv.Cells 1066
.-
dl►. .
Summary 1067
Further Reading 106 8Problems 1069
. ,1
28 Regulation of Gene Expression 107 2Principles of Gene Regulation 1074
,RNA Polymerase Binds to DNA at Promoters 107 4
Transcription Initiation Is Regulated by Proteins That Bin dto or near Promoters 1074
page 114 5Most Prokaryotic Genes Are Regulated in Units Called
Operons 107 7
The lac Operon Is Subject to Negative Regulation 1078
Regulatory Proteins Have Discrete DNA-Binding Domains 108 0
Regulatory Proteins Also Have Protein-Protein Interaction
Cloning Vectors Allow Amplification of Inserted DN ADomains 1084
Segments 1124
Regulation of Gene Expression in Prokaryotes 1085
Isolating a Gene from a Cellular Chromosome 112 8The /ac Operon Is Subject to Positive Regulation 1086
Cloning a Gene Often Requires a DNA Library 112 8The ara Operon Undergoes Both Positive and Negative Regulation
Specific DNA Sequences Can Be Amplified 112 9by a Single Regulatory Protein 1088
Hybridization Allows the Detection of Specific Sequences 113 1Many Genes for Amino Acid Biosynthesis Are Regulated by
n Box 29-1 A Potent Weapon in Forensic Medicine 1132Transcription Attenuation 1091
DNA Microarrays Provide Compact Libraries for Studying Gene sInduction of the SOS Response Requires the Destruction of
and Their Expression 113 4Repressor Proteins 109 4
Synthesis of Ribosomal Proteins Is Coordinated with rRNA
Applications of Recombinant DNA Technology 113 5
Synthesis 1095
Cloned Genes Can Be Expressed 113 5
Some Genes Are Regulated by Genetic Recombination 1097
Cloned Genes Can Be Altered 113 6
Regulation of Gene Expression in Eukaryotes 1099
Yeast Is an Important Eukaryotic Host for Recombinan tDNA 1138
Transcriptionally Active Chromatin Is Structurally Distinct from
Very Large DNA Segments Can Be Cloned in Yeast Artificia lInactive Chromatin 1100Chromosomes 113 8
Modifications Increase the Accessibility of DNA 1100
n Box 29-2 The Human Genome and Human Gene Therapy 1140Chromatin Is Remodeled by Acetylation and Nucleosomal
Cloning in Plants Is Aided by a Bacterial Plant Parasite 114 0Displacements 1100
Many Eukaryotic Promoters Are Positively Regulated 1101
Cloning in Animal Cells Points the Way to Human Gen eTherapy 114 5
DNA-Binding Transactivators and Coactivators Facilitate Assembly
Recombinant DNA Technology Yields New Product sof the General Transcription Factors 1102
and Choices 114 7Three Classes of Proteins Are Involved in Transcriptiona l
Activation 1102
Summary 1148
Further Reading 114 9
The Genes Required for Galactose Metabolism in Yeast Are
Problems 1150
Subject to Both Positive and Negative Regulation 110 4
DNA-Binding Transactivators Have a Modular Structure 1106
Appendix A Common Abbreviations in th e
Eukaryotic Gene Expression Can Be Regulated by Intercellular and
Biochemical Research Literature AP- 1Intracellular Signals 110 6
Regulation Can Occur through Phosphorylation of Nuclear
Appendix B Abbreviated Solutions to Problems AP- 4Transcription Factors 1108
Many Eukaryotic mRNAs Are Subject to Translational
Illustration Credits IC-1Repression 1108
Development Is Controlled by Cascades of Regulatory
Glossary G-1Proteins 1109
Index 1- 1Summary 1115
Further Reading 111 6Problems 1117
29 Recombinant DNA Technology 111 9DNA Cloning : The Basics 111 9
Restriction Endonucleases and DNA Ligase Yield Recombinan tDNA 1120