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SIXTH EDITION
Biochemistry
Jeremy M . Berg
John L. Tymoczko
Lubert Stryer
Part I THE MOLECULAR DESIGN OF LIF E
1
Biochemistry : An Evolving Science 1
2 Protein Composition and Structure 2 5
3 Exploring Proteins and Proteomes 6 5
4 DNA, RNA, and the Flow of Geneti cInformation 107
5 Exploring Genes and Genomes 13 4
6 Exploring Evolution and Bioinformatics 164
7 Hemoglobin: Portrait of a Protein in Action 18 3
8 Enzymes: Basic Concepts and Kinetics 20 5
9 Catalytic Strategies 241
10 Regulatory Strategies 27 5
11 Carbohydrates 30 3
12 Lipids and Cell Membranes 326
13 Membrane Channels and Pumps 35 1
14 Signal-Transduction Pathways 38 1
Part II TRANSDUCING AND STORING ENERGY
15 Metabolism: Basic Concepts and Design 40 916 Glycolysis and Gluconeogenesis 43 3
17 The Citric Acid Cycle 47 518 Oxidative Phosphorylation 502
19 The Light Reactions of Photosynthesis 54 120 The Calvin Cycle and the Pentose Phosphate
Pathway 56 521 Glycogen Metabolism 59 2
22 Fatty Acid Metabolism 61 7
23 Protein Turnover and Amino Acid Catabolism 649
Part III SYNTHESIZING THE MOLECULES OF LIF E
24 The Biosynthesis of Amino Acids 67 9
25 Nucleotide Biosynthesis 70 926 The Biosynthesis of Membrane Lipid s
and Steroids 73 2
27 The Integration of Metabolism 76 0
28 DNA Replication, Repair, and Recombination 78 3
29 RNA Synthesis and Processing 821
30 Protein Synthesis 857
31 The Control of Gene Expression 892
Part IV RESPONDING TO ENVIRONMENTA LCHANGES
32 Sensory Systems 921
33 The Immune System 94534 Molecular Motors 977
3S Drug Development 1001
Preface
v
Part I THE MOLECULAR DESIGN OF LIFE
Chapter 1 Biochemistry: An Evolving Science 1
1 .1 Biochemical Unity Underlies Biological Diversity 1
1 .2 DNA Illustrates the Interplay Betwee nForm and Function
4
DNA Is Constructed from Four Building Blocks
4
Two Single Strands of DNA Combine to Form aDouble Helix
5
DNA Structure Explains Heredity and the Storageof Information
5
1 .3 Concepts from Chemistry Explain th eProperties of Biological Molecules
6
The Double Helix Can Form from Its Component Strands 6
Covalent and Noncovalent Bonds Are Important for th eStructure and Stability of Biological Molecules
7
The Double Helix Is an Expression of the Rule sof Chemistry
1 0
The Laws of Thermodynamics Govern the Behavio rof Biochemical Systems
1 1
Heat Is Released in the Formation of the Double Helix
1 2
Acid-Base Reactions Are Central in Man yBiochemical Reactions
1 4
Acid-Base Reactions Can Disrupt the Double Helix
1 5
Buffers Regulate pH in Organisms and in the Laboratory 1 6
1 .4 The Genomic Revolution Is Transformin gBiochemistry and Medicine
1 7
The Sequencing of the Human Genome Is aLandmark in Human History
1 8
Genome Sequences Encode Proteins and Patternsof Expression
1 8
Individuality Depends on the Interplay Betwee nGenes and Environment
2 0
APPENDIX : Visualing Molecular Structures I :Small Molecules
2 2
Chapter 2 Protein Composition an dStructure
25
2 .1 Proteins Are Built from a Repertoir eof 20 Amino Acids
27
2.2 Primary Structure : Amino Acids Are Linkedby Peptide Bonds to Form Polypeptide Chains
34
Proteins Have Unique Amino Acid Sequences Specifiedby Genes
36
Polypeptide Chains Are Flexible Yet Conformationally
Proteins Must Be Released from the Cell to Be Purified
6 7Restricted
37
Proteins Can Be Purified According to Solubility,
2.3 Secondary Structure : Polypeptide Chains Can
Size, Charge, and Binding Activity
6 8
Fold into Regular Structures Such As the Alpha
Proteins Can Be Separated by Gel Electrophoresi s
Helix, the Beta Sheet, and Turns and Loops
40
and Displayed
7 1
The Alpha Helix Is a Coiled Structure Stabilized by
A Protein Purification Scheme Can Be Quantitativel y
Intrachain Hydrogen Bonds
40
Evaluated
7 4
Beta Sheets Are Stabilized by Hydrogen Bonding
Ultracentrifugation Is Valuable for Separatin g
Between Polypeptide Strands
42
Biomolecules and Determining Their Masses
7 6
Polypeptide Chains Can Change Direction by Making
3.2 Amino Acid Sequences Can Be Determine d
Reverse Turns and Loops
44
by Automated Edman Degradation
78
Fibrous Proteins Provide Structural Support for Cells
Proteins Can Be Specifically Cleaved into Small Peptide sand Tissues
45
to Facilitate Analysis
80
2.4 Tertiary Structure : Water-Soluble Proteins Fold
Amino Acid Sequences Are Sources of Many
into Compact Structures with Nonpolar Cores
46
Kinds of Insight
82
2.5 Quaternary Structure : Polypeptide Chains
Recombinant DNA Technology Has Revolutionize dProtein Sequencing
8 3Can Assemble into Multisubunit Structures
493.3 Immunology Provides Important Technique swith Which to Investigate Proteins
84
Antibodies to Specific Proteins Can Be Generated
84
Monoclonal Antibodies with Virtually Any Desire dSpecificity Can Be Readily Prepared
8 5
Proteins Can Be Detected and Quantitated by Using anEnzyme-Linked Immunosorbent Assay
8 7
Western Blotting Permits the Detection of Protein sSeparated by Gel Electrophoresis
8 8
Fluorescent Markers Make Possible the Visualizatio nof Proteins in the Cell
892.6 The Amino Acid Sequence of a Protein
3 .4 Peptides Can Be Synthesized by Automate dDetermines Its Three-Dimensional Structure
50
Solid-Phase Methods
90Amino Acids Have Different Propensities for Forming
3 .5 Mass Spectrometry Provides Powerful Tool sAlpha Helices, Beta Sheets, and Beta Turns
52for Protein Characterization and Identification
93Protein Misfolding and Aggregation Are Associated withSome Neurological Diseases
53
The Mass of a Protein Can Be Precisely Determine d
Protein Folding Is a Highly Cooperative Process
55
by Mass Spectrometry
9 3
Proteins Fold by Progressive Stabilization
Individual Protein Components of Large Protein Complexe s
of Intermediates Rather Than by Random Search
55
Can Be Identified by MALDI-TOF Mass Spectrometry 9 4
Prediction of Three-Dimensional Structure from
3 .6 Three-Dimensional Protein Structure Can B eSequence Remains a Great Challenge
57
Determined by X-ray Crystallography and NM RProtein Modification and Cleavage Confer New
Spectroscopy
96Capabilities
57
X-ray Crystallography Reveals Three-Dimensiona lAPPENDIX : Visualizing Molecular Structures II : Proteins 61
Structure in Atomic Detail
9 6
Nuclear Magnetic Resonance Spectroscopy CanChapter 3 Exploring Proteins and
Reveal the Structures of Proteins in Solution
9 8Proteomes
65Chapter 4 DNA, RNA, and the Flow
The Proteome Is the Functional Representation
of Genetic Information
107of the Genome
66
3.1 The Purification of Proteins Is an Essential
4 .1 A Nucleic Acid Consists of Four Kinds o fFirst Step in Understanding Their Function
66
Bases Linked to a Sugar-Phosphate Backbone
108
The Assay : How Do We Recognize the Protein
RNA and DNA Differ in the Sugar ComponentThat We Are Looking For?
67
and One of the Bases
108
Nucleotides Are the Monomeric Units
PCR Is a Powerful Technique in Medical Diagnostics ,of Nucleic Acids
109
Forensics, and Studies of Molecular Evolution
14 1
4.2 A Pair of Nucleic Acid Chains with omplementary
5 .2 Recombinant DNA Technology HasSequences Can Form a Double-Helical Structure
111
Revolutionized All Aspects of Biology
142
The Double Helix Is Stabilized by Hydrogen Bonds and
Restriction Enzymes and DNA Ligase Are Key Tool sHydrophobic Interactions
111
in Forming Recombinant DNA Molecules
14 2
The Double Helix Facilitates the Accurate Transmission
Plasmids and Lambda Phage Are Choice Vectorsof Hereditary Information
113
for DNA Cloning in Bacteria
14 3
The Double Helix Can Be Reversibly Melted
114
Bacterial and Yeast Artificial Chromosomes
14 5
Some DNA Molecules Are Circular and Supercoiled
115
Specific Genes Can Be Cloned from Digests of
Single-Stranded Nucleic Acids Can Adopt
Genomic DNA
14 6
Elaborate Structures
116
Proteins with New Functions Can Be Created Throug h
4.3 DNA Is Replicated by Polymerases That
Directed Changes in DNA
14 7
Take Instructions from Templates
117
5 .3 Complete Genomes Have Been Sequencedand Analyzed
149DNA Polymerase Catalyzes Phosphodiester-Bon dFormation
117
The Genomes of Organisms Ranging from Bacteri a
The Genes of Some Viruses Are Made of RNA
118
to Multicellular Eukaryotes Have Been Sequenced
14 9
The Sequencing of the Human Genom e4.4 Gene Expression Is the Transformation
Has Been Finished
15 0
of DNA Information into Functional Molecules 119
Comparative Genomics Has Become a Powerfu l
Several Kinds of RNA Play Key Roles in Gene
Research Tool
15 1
Expression
119
Gene-Expression Levels Can Be Comprehensively
All Cellular RNA Is Synthesized by RNA Polymerases
120
Studied
15 1
RNA Polymerases Take Instructions from DNA Templates 121
5 .4 Eukaryotic Genes Can Be Manipulate dTranscription Begins Near Promoter Sites and Ends at
with Considerable Precision
15 2Terminator Sites
122Complementary DNA Prepared from mRNA Ca n
Transfer RNA Is the Adaptor Molecules in Protein
Be Expressed in Host Cells
15 2Synthesis
123
New Genes Inserted into Eukaryotic Cells Can B e4.5 Amino Acids Are Encoded by Groups
Efficiently Expressed
15 4
of Three Bases Starting from a Fixed Point
124
Transgenic Animals Harbor and Express Genes Tha t
Major Features of the Genetic Code
125
Were Introduced into Their Germ Lines
15 5
Messenger RNA Contains Start and Stop Signals
Gene Disruption Provides Clues to Gene Function
15 5
for Protein Synthesis
126
RNA Interference Provides an Additional Too lfor Disrupting Gene Expression
15 7The Genetic Code Is Nearly Universal
126Tumor-Inducing Plasmids Can Be Used to Introduce
4.6 Most Eukaryotic Genes Are Mosaics
New Genes into Plant Cells
15 7of Introns and Exons
127
Human Gene Therapy Holds Great Promis e
RNA Processing Generates Mature RNA
128
for Medicine
15 8
Many Exons Encode Protein Domains
128
Chapter 6 Exploring Evolution an dChapter 5 Exploring Genes and Genomes 134 Bioinformatics
164
5.1 The Exploration of Genes Relies on Key Tools 135 6 .1 Homologs Are Descended from a Commo n
Restriction Enzymes Split DNA into Specific Fragments 135
Ancestor
16 5
Restriction Fragments Can Be Separated by
6.2 Statistical Analysis of Sequence AlignmentsGel Electrophoresis and Visualized
136
Can Detect Homology
166DNA Can Be Sequenced by Controlled Termination
The Statistical Significance of Alignments Can B eof Replication
138
Estimated by Shuffling
16 8
DNA Probes and Genes Can Be Synthesized by
Distant Evolutionary Relationships Can Be Detecte dAutomated Solid-Phase Methods
139
Through the Use of Substitution Matrices
16 8
Selected DNA Sequences Can Be Greatly Amplified
Databases Can Be Searched to Identifyby the Polymerase Chain Reaction
140
Homologous Sequences
171
6.3 Examination of Three-Dimensional Structur eEnhances Our Understanding of Evolutionar yRelationships
172Tertiary Structure Is More Conserved ThanPrimary Structure
17 3
Knowledge of Three-Dimensional Structures CanAid in the Evaluation of Sequence Alignments
174
Repeated Motifs Can Be Detected by AligningSequences with Themselves
17 4
Convergent Evolution Illustrates Commo nSolutions to Biochemical Challenges
17 5
Comparison of RNA Sequences Can Be a Sourc eof Insight into RNA Secondary Structures
17 6
6.4 Evolutionary Trees Can Be Constructe don the Basis of Sequence Information
177
6.5 Modern Techniques Make the ExperimentalExploration of Evolution Possible
178
Ancient DNA Can Sometimes Be Amplified andSequenced
17 8
Molecular Evolution Can Be Examined Experimentally 17 8
Chapter 7 Hemoglobin : Portrait ofa Protein in Action
183
7.1 Myoglobin and Hemoglobin Bind Oxyge nat Iron Atoms in Herne
184
The Structure of Myoglobin Prevents the Releas eof Reactive Oxygen Species
18 5
Human Hemoglobin Is an Assembly of Fou rMyoglobin-like Subunits
18 6
7.2 Hemoglobin Binds Oxygen Cooperatively
187
Oxygen Binding Markedly Changes the QuaternaryStructure of Hemoglobin
18 8
Hemoglobin Cooperativity Can Be Potentiall yExplained by Several Models
18 9
Structural Changes at the Herne Groups Ar eTransmitted to the a1ß1-a2132 Interface
19 0
2,3-Bisphosphoglycerate in Red Cells Is Crucial inDetermining the Oxygen Affinity of Hemoglobin
19 0
7.3 Hydrogen Ions and Carbon Dioxide Promotethe Release of Oxygen: The Bohr Effect
192
7.4 Mutations in Genes Encoding Hemoglobi nSubunits Can Result in Disease
194
Sickle-Cell Anemia Results from the Aggregatio nof Mutated Deoxyhemoglobin Molecules
19 5
Thalassemia Is Caused by an Imbalanced Productionof Hemoglobin Chains
19 6
The Accumulation of Free Alpha-HemoglobinChains Is Prevented
19 7
Additional Globins Are Encoded in the Human Genome 19 7
APPENDIX: Binding Models Can Be Formulated inQuantitative Terms : The Hill Plot and th eConcerted Model
19 9
Chapter 8 Enzymes: Basic Concept sand Kinetics
205
8.1 Enzymes Are Powerful and Highly Specifi cCatalysts
206Many Enzymes Require Cofactors for Activity
20 7
Enzymes May Transform Energy from One For minto Another
20 7
8.2 Free Energy Is a Useful Thermodynami cFunction for Understanding Enzymes
208The Free-Energy Change Provides Information Abou tthe Spontaneity but Not the Rate of a Reaction
20 8
The Standard Free-Energy Change of a Reactio nIs Related to the Equilibrium Constant
20 8
Enzymes Alter Only the Reaction Rate and Notthe Reaction Equilibrium
21 0
8.3 Enzymes Accelerate Reactions by Facilitatingthe Formation of the Transition State
21 1
The Formation of an Enzyme-Substrate Complex I sthe First Step in Enzymatic Catalysis
21 3
The Active Sites of Enzymes Have Some Commo nFeatures
21 4
The Binding Energy Between Enzyme and SubstrateIs Important for Catalysis
21 5
8.4 The Michaelis-Menten Equation Describe sthe Kinetic Properties of Many Enzymes
216Kinetics Is the Study of Reaction Rates
21 6
The Steady-State Assumption Facilitates aDescription of Enzyme Kinetics
21 7
KM and Vmax Values Can Be Determined b ySeveral Means
22 0
KM and Vmax Values Are Important Enzym eCharacteristics
22 0
kcat /KM Is a Measure of Catalytic Efficiency
22 1
Most Biochemical Reactions Include Multipl eSubstrates
22 3
Allosteric Enzymes Do Not Obey Michaelis-Mente nKinetics
224
8.5 Enzymes Can Be Inhibited by Specific
Type II Restriction Enzymes Have a Catalytic Cor e
Molecules
225
in Common and Are Probably Related by Horizonta l
Reversible Inhibitors Are Kinetically Distinguishable
226
Gene Transfer
26 6
Irreversible Inhibitors Can Be Used to Map the
9.4 Nucleoside Monophosphate Kinase sActive Site
228
Catalyze Phosphoryl-Group Transfer WithoutTransition-State Analogs Are Potent Inhibitors
Promoting Hydrolysis
267of Enzymes
231NMP Kinases Are a Family of Enzymes Containing
Catalytic Antibodies Demonstrate the Importance
P-Loop Structures
26 7of Selective Binding of the Transition Stateto Enzymatic Activity
232
Magnesium or Manganese Complexes of Nucleosid eTriphosphates Are the True Substrates for Essentiall y
PinenBacterial
ibly a 1 InactiSynthesi
svates a Key Enzyme232
All NTP-Dependent Enzymes
26 8
APPENDIX: Enzymes Are Classified on the Basis
ATP Binding Induces Large Conformational Changes
269
of the Types of Reactions That They Catalyze
236
P-Loop NTPase Domains Are Present in a Range o fImportant Proteins
27 0
Chapter 9 Catalytic Strategies
241Chapter 10 Regulatory Strategies
275A Few Basic Catalytic Principles Are Used byMany Enzymes
242
10 .1 Aspartate Transcarbamoylase Is Allostericall y
9.1 Proteases Facilitate a Fundamentally
Inhibited by the End Product of Its Pathway
276
Difficult Reaction
243
Allosterically Regulated Enzymes Do Not Follo w
Chymotrypsin Possess a Highly Reactive Serine Residue 243
Michaelis Menten Kinetics
27 7
Chymotrypsin Action Proceed in Two Steps Linked
ATCase Consists of Separable Catalytic an d
by a Covalently Bound Intermediate
244
Regulatory Subunits
27 7
Serine Is Part of a Catalytic Triad That Also Includes
Allosteric Interactions in ATCase Are Mediated b y
Histidine and Aspartate
245
Large Changes in Quaternary Structure
27 8
Catalytic Triads Are Found in Other Hydrolytic
Allosteric Regulators Modulate the T to R
Enzymes
248
Equilibrium
28 1
The Catalytic Triad Has Been Dissected by Site-
10.2 Isozymes Provide a Means of Regulatio n
Directed Mutagenesis
250
Specific to Distinct Tissues an d
Cysteine, Aspartyl, and Metalloproteases Are Other
Developmental Stages
283
Major Classes of Peptide-Cleaving Enzymes
251
10.3 Covalent Modification Is a Means ofProtease Inhibitors Are Important Drugs
253
Regulating Enzyme Activity
283
9.2 Carbonic Anhydrases Make a Fast Reaction
Phosphorylation Is a Highly Effective Means ofFaster
254
Regulating the Activities of Target Proteins
28 4
Carbonic Anhydrase Contains a Bound Zinc Ion
Cyclic AMP Activates Protein Kinase A by Altering th e
Essential for Catalytic Activity
255
Quaternary Structure
28 7
Catalysis Entails Zinc Activation of a Water Molecule
256
ATP and the Target Protein Bind to a Deep Cleft in th e
A Proton Shuttle Facilitates Rapid Regeneration
Catalytic Subunit of Protein Kinase A
28 8
of the Active Form of the Enzyme
257
10.4 Many Enzymes Are Activated by Specifi cConvergent Evolution Has Generated Zinc-Based
Proteolytic Cleavage
288Active Sites in Different Carbonic Anhydrases
258Chymotrypsinogen Is Activated by Specific Cleavage
9.3 Restriction Enzymes Perform Highly Specific
of a Single Peptide Bond
28 9
DNA-Cleavage Reactions
259
Proteolytic Activation of Chymotrypsinogen Lead s
Cleavage Is by In-Line Displacement of 3'-Oxygen
to the Formation of a Substrate Binding Site
29 0
from Phosphorus by Magnesium-Activated Water
260
The Generation of Trypsin from Trypsinogen Leads
Restriction Enzymes Require Magnesium for
to the Activation of Other Zymogens
29 1
Catalytic Activity
262
Some Proteolytic Enzymes Have Specific Inhibitors
29 1
The Complete Catalytic Aparatus Is Assembled
Blood Clotting Is Accomplished by a Cascade
Only Within Complexes of Cognate DNA Molecules,
of Zymogen Activations
29 3
Ensuring Specificity
263
Fibrinogen Is Converted by Thrombin into a Fibrin Clot
293
Prothrombin Is Readied for Activation by
Fatty Acids Vary in Chain Length and Degree of
a Vitamin K-Dependent Modification
295
Unsaturation
32 8
Hemophilia Revealed an Early Step in Clotting
296
12 .2 There Are Three Common Types o fThe Clotting Process Must Be Regulated
296
Membrane Lipids
329
Phospholipids Are the Major Class of Membrane
Chapter 11 Carbohydrates
303
Lipids
32 9
Membrane Lipids Can Include Carbohydrat e11 .1 Monosaccharides Are Aldehydes or Ketones
Moieties
33 1
with multiple Hydroxyl Groups
304
Cholesterol Is a Lipid Based on a Steroid Nucleus
33 1
Pentoses and Hexoses Cyclize to Form Furanose
Archael Membranes Are Built from Ether Lipid s
and Pyranose Rings
306
with Branched Chains
33 1
Pyranose and Furanose Rings Can Assume Different
A Membrane Lipid Is an Amphipathic Molecul e
Conformations
308
Containing a Hydrophilic and a Hydrophobic Moiety
33 2
Monosaccharides Are Joined to Alcohols and Amines
12 .3 Phospholipids and Glycolipids Readily For mThrough Glycosidic Bonds
309
Bimolecular Sheets in Aqueous Media
333
Phosphorylated Sugars Are Key Intermediates in
Lipid Vesicles Can Be Formed from Phospholipids
33 4Energy Generation and Biosyntheses
310Lipid Bilayers Are Highly Impermeable to Ion s
11 .2 Complex Carbohydrates Are Formed by
and Most Polar Molecules
33 5
the Linkage of Monosaccharides
310 12.4 Proteins Carry Out Most MembraneSucrose, Lactose, and Maltose Are the Common
Processes
336Disaccharides
310Proteins Associate with the Lipid Bilayer in a Variet y
Glycogen and Starch Are Mobilizable Stores of Glucose 311
of Ways
33 6Cellulose, the Major Structural Polymer of Plants,
Proteins Interact with Membranes in a Variet yConsists of Linear Chains of Glucose Units
312
of Ways
33 6Glycosaminoglycans Are Anionic Polysaccharide
Some Proteins Associate with Membranes Throug hChains Made of Repeating Disaccharide Units
312
Covalently Attached Hydrophobic Groups
34 0Specific Enzymes Are Responsible for Oligosaccharide
Transmembrane Helices Can Be Accurately Predicte dAssembly
314
from Amino Acid Sequences
34 0
11 .3 Carbohydrates Can Be Attached to Proteins
12.5 Lipids and Many Membrane Proteins Diffus eto Form Glycoproteins
316
Rapidly in the Plane of the Membrane
342
Carbohydrates Can Be Linked to Proteins Through
The Fluid Mosaic Model Allows Lateral Movemen tAsparagine (N-Linked) or Through Serine or
but Not Rotation Through the Membrane
34 3Threonine (O Linked) Residues
316
Membrane Fluidity Is Controlled by Fatty AcidProtein Glycosylation Takes Place in the Lumen of the
Composition and Cholesterol Content
34 3Endoplasmic Reticulum and in the Golgi Complex
317All Biological Membranes Are Asymmetric
34 5Errors in Glycosylation Can Result in Pathologica lConditions
318
12.6 Eukaryotic Cells Contain Compartments
Oligosaccharides Can Be "Sequenced"
319
Bounded by Internal Membranes
345
11 .4 Lectins Are Specific Carbohydrate-Bindin gProteins
320 Chapter 13 Membrane Channels andLectins Promote Interaction Between Cells
320
Pumps
351Influenza Virus Binds to Sialic Acid Residues
321The Expression of Transporters Largely Defines th e
Chapter 12 Lipids and Cell Membranes
326
Metabolic Activities of a Given Cell Type
35 2
13.1 The Transport of Molecules AcrossMany Common Features Underlie the Diversity
a Membrane May Be Active or Passive
352of Biological Membranes
327
Many Molecules Require Protein Transporters t o12 .1 Fatty Acids Are Key Constituents of Lipids 327
Cross Membranes
352
Fatty Acid Names Are Based on Their Parent
Free Energy Stored in Concentration GradientsHydrocarbons
327
Can Be Quantified
353
13 .2 Two Families of Membrane Proteins Use AT PHydrolysis to Pump Ions and Molecules Acros sMembranes
354
P-Type ATPases Couple Phosphorylation an dConformational Changes to Pump Calcium Ion sAcross Membranes
35 4
Digitalis Specifically Inhibits the Na +-K+ Pump byBlocking Its Dephosphorylation
35 7
P-Type ATPases Are Evolutionarily Conserve dand Play a Wide Range of Roles
35 8
Multidrug Resistance Highlights a Family of Membran ePumps with ATP-Binding Cassette Domains
35 8
13.3 Lactose Permease Is an Archetype of Secondar yTransporters That Use One Concentration Gradientto Power the Formation of Another
360
13.4 Specific Channels Can Rapidly TransportIons Across Membranes
362
Action Potentials Are Mediated by Transien tChanges in Na' and K + Permeability
36 2
Patch-Clamp Conductance Measurements Reveal th eActivities of Single Channels
36 3
The Structure of a Potassium Ion Channel Is a nArchetype for Many Ion-Channel Structures
36 4
The Structure of the Potassium Ion Channel Reveal sthe Basis of Ion Specificity
36 5
The Structure of the Potassium Ion Channel ExplainsIts Rapid Rate of Transport
36 7
Voltage Gating Requires Substantial ConformationalChanges in Specific Ion-Channel Domains
36 8
A Channel Can Be Inactivated by Occlusion of the Pore :The Ball-and-Chain Model
369
The Acetylcholine Receptor Is an Archetypefor Ligand-Gated Ion Channels
37 0
Action Potentials Integrate the Activities of Several IonChannels Working in Concert
372
13.5 Gap Junctions Allow Ions and Smal lMolecules to Flow Betwee nCommunicating Cells
373
13.6 Specific Channels Increase the Permeabilityof Some Membranes to Water
374
Chapter 14 Signal-Transduction Pathways 38 1
Signal-Transduction Depends on Molecular Circuits
382
14.1 Heterotrimeric G Proteins Transmit Signal sand Reset Themselves
383
Ligand Binding to 7 TM Receptors Leads to th eActivation of Heterotrimeric G Proteins
38 4
Activated G Proteins Transmit Signals by Bindin gto Other Proteins
38 5
Cyclic AMP Stimulates the Phosphorylation of ManyTarget Proteins by Activating Protein Kinase A
38 6
G Proteins Spontaneously Reset Themselves ThroughGTP Hydrolysis
38 7
Some 7 TM Receptors Activate the PhosphoinositideCascade
38 8
Calcium Ion Is a Widely Used Second Messenger
38 9
Calcium Ion Often Activates the Regulatory ProteinCalmodulin
39 0
14.2 Insulin Signaling: Phosphorylation CascadesAre Central to Many Signal-Transductio nProcesses
39 1
The Insulin Receptor Is a Dimer That Closes Around aBound Insulin Molecule
39 2
Insulin Binding Results in the Cross-Phosphorylationand Activation of the Insulin Receptor
39 2
The Activated Insulin Receptor Kinase Initiates aKinase Cascade
39 3
Insulin Signaling Is Terminated by the Actio nof Phosphatases
39 5
14.3 EGF Signaling : Signal-Transduction PathwaysAre Poised to Respond
395
EGF Binding Results in the Dimerization of th eEGF Receptor
39 6
The EGF Receptor Undergoes Phosphorylation of It sCarboxyl-Terminal Tail
39 7
EGF Signaling Leads to the Activation of Ras, a Smal lG Protein
39 7
Activated Ras Initiates a Protein Kinase Cascade
39 8EGF Signaling Is Terminated by Protein Phosphatase sand the Intrinsic GTPase Activity of Ras
39 8
14.4 Many Elements Recur with Variation i nDifferent Signal-Transduction Pathways
399
14 .5 Defects in Signal-Transduction Pathway sCan Lead to Cancer and Other Diseases
400
Monoclonal Antibodies Can Be Used to Inhibi tSignal-Transduction Pathways Activated in Tumors
40 1
Protein Kinase Inhibitors Can Be Effective Anticance rDrugs
40 1Cholera and Whooping Cough Are Due to AlteredG-Protein Activity
401
Part II TRANSDUCING AND STORING
The Six-Carbon Sugar Is Cleaved into Two Three -ENERGY
Carbon Fragments
43 8Mechanism : Triose Phosphate Isomerase Salvages aThree-Carbon Fragment
43 9Chapter 15 Metabolism: Basic Concepts
The Oxidation of an Aldehyde to an Acid Powers theand Design
409
Formation of a Compound with High Phosphoryl -Transfer Potential
44 015 .1 Metabolism Is Composed of Many Coupled,
Mechanism: Phosphorylation Is Coupled to the Oxidation ofInterconnecting Reactions
410
Glyceraldehyde 3-phosphate by a Thioester Intermediate 44 2Metabolism Consists of Energy-Yielding and Energy-
ATP Is Formed by Phosphoryl Transfer fro mRequiring Reactions
410
1,3-Bisphosphoglycerate
44 3A Thermodynamically Unfavorable Reaction Can
Additional ATP Is Generated with the Formatio nBe Driven by a Favorable Reaction
411
of Pyruvate
44 4
15 .2 ATP Is the Universal Currency of Free
Two ATP Molecules Are Formed in the Conversion of
Energy in Biological Systems
412
Glucose into Pyruvate
44 6NAD + Is Regenerated from the Metabolism of Pyruvate 44 6
ATP Hydrolysis Is Exergonic
412
Fermentations Provide Usable Energy in th eATP Hydrolysis Drives Metabolism by Shifting the
Absence of Oxygen
44 8Equilibrium of Coupled Reactions
413
The Binding Site for NAD + Is Similar in Man yThe High Phosphoryl Potential of ATP Results from
Dehydrogenases
44 8Structural Differences Between ATP and Its Hydrolysis
Fructose and Galactose Are Converted into Glycolyti cProducts
415
Intermediates
449Phosphoryl-Transfer Potential Is an Important Form
Many Adults Are Intolerant of Milk Because They Ar eof Cellular Energy Transformation
416
Deficient in Lactase
45 115 .3 The Oxidation of Carbon Fuels Is an
Galactose Is Highly Toxic If the Transferase Is Missing 45 1Important Source of Cellular Energy
417
16 .2 The Glycolytic Pathway Is Tightly Controlled 45 2Compounds with High Phosphoryl-Transfer Potential
Glycolysis in Muscle Is Regulated to Meet the NeedCan Couple Carbon Oxidation to ATP Synthesis
418
for ATP
45 2Ion Gradients Across Membranes Provide
The Regulation of Glycolysis in the Liver Reflects thean Important Form of Cellular Energy That
Biochemical Versatility of the Liver
45 5Can Be Coupled to ATP Synthesis
418A Family of Transporters Enables Glucose to Ente r
Energy from Foodstuffs Is Extracted in Three Stages
419
and Leave Animal Cells
45 6
15.4 Metabolic Pathways Contain Many
Cancer and Exercise Training Affect Glycolysis in aRecurring Motifs
420
Similar Fashion
45 7
Activated Carriers Exemplify the Modular Design
16.3 Glucose Can Be Synthesized fro mand Economy of Metabolism
420
Noncarbohydrate Precursors
458Many Activated Carriers Are Derived from Vitamins
42 3Key Reactions Are Reiterated Throughout Metabolism 425
Gluconeogenesis Is Not a Reversal of Glycolysis
460
Metabolic Processes Are Regulated in Three Principal Ways 428
The Conversion of Pyruvate into Phosphoenolpyruvat e
Aspects of Metabolism May Have Evolved from an
Begins with the Formation of Oxaloacetate
46 1
RNA World
429
Oxaloacetate Is Shuttled into the Cytoplasm an dConverted into Phosphoenolpyruvate
46 2
The Conversion of Fructose 1,6-bisphosphate int oChapter 16 Glycolysis and Gluconeogenesis 433
Fructose 6-phosphate and Orthophosphate Is anIrreversible Step
46 3
Glucose Is Generated from Dietary Carbohydrates
434
The Generation of Free Glucose Is an Importan tGlucose Is an Important Fuel for Most Organisms
435
Control Point
46 3
16.1 Glycolysis Is an Energy-Conversion Pathway in
Six High Transfer Potential Phosphoryl Groups Ar e
Many Organisms
435
Spent in Synthesizing Glucose from Pyruvate
46 4
16.4 Gluconeogenesis and Glycolysis AreHexokinase Traps Glucose in the Cell and Begins
Reciprocally Regulated
464Glycolysis
43 5
Fructose 1,6-bisphosphate Is Generated from Glucose
Energy Charge Determines Whether Glycolysi s
6-phosphate
437
or Gluconeogenesis Will Be Most Active
465
The Balance Between Glycolysis and Gluconeogenesi sin the Liver Is Sensitive to Blood-Glucos eConcentration
46 6
Substrate Cycles Amplify Metabolic Signals andProduce Heat
46 7
Lactate and Alanine Formed by ContractingMuscles Are Used by Other Organs
46 8
Glycolysis and Gluconeogenesis Are Evolutionaril yIntertwined
46 9
Chapter 17 The Citric Acid Cycle
475
The Citric Acid Cycle Harvests High-Energy Electrons 47 6
17.1 Pyruvate Dehydrogenase Links Glycolysisto the Citric Acid Cycle
477
Mechanism: The Synthesis of Acetyl Coenzyme A fro mPyruvate Requires Three Enzymes and Five Coenzymes 47 8
Flexible Linkages Allow Lipoamide to Move BetweenDifferent Active Sites
48 0
17.2 The Citric Acid Cycle Oxidize sTwo-Carbon Units
482
Citrate Synthase Forms Citrate from Oxaloacetat eand Acetyl Coenzyme A
48 2
Mechanism: The Mechanism of Citrate SynthasePrevents Undesirable Reactions
48 2
Citrate Is Isomerized into Isocitrate
48 4
Isocitrate Is Oxidized and Decarboxylated t oa-Ketoglutarate
484
Succinyl Coenzyme A Is Formed by the OxidativeDecarboxylation of a-Ketoglutarate
48 5
A Compound with High Phosphoryl-Transfer Potentia lIs Generated from Succinyl Coenzyme A
48 5
Mechanism : Succinyl Coenzyme A Synthetase TransformsTypes of Biochemical Energy
48 6
Oxaloacetate Is Regenerated by the Oxidationof Succinate
48 7
The Citric Acid Cycle Produces High-Transfer-Potentia lElectrons, GTP, and CO2
48 8
17.3 Entry to the Citric Acid Cycleand Metabolism Through It Are Controlled
490
The Pyruvate Dehydrogenase Complex Is Regulate dAllosterically and by Reversible Phosphorylation
49 0
The Citric Acid Cycle Is Controlled at Several Points
49 2
17.4 The Citric Acid Cycle Is a Source ofBiosynthetic Precursors
493
The Citric Acid Cycle Must Be Capable of BeingRapidly Replenished
49 3
The Disruption of Pyruvate Metabolism Is the Causeof Beriberi and Poisoning by Mercury and Arsenic
49 4
The Citric Acid Cycle May Have Evolved fro mPreexisting Pathways
495
175 The Glyoxylate Cycle Enables Plants an dBacteria to Grow on Acetate
495
Chapter 18 Oxidative Phosphorylation
502
Oxidative Phosphorylation Couples the Oxidation o fCarbon Fuels to ATP Synthesis with a Proton Gradient 50 2
18.1 Oxidative Phosphorylation in Eukaryotes Take sMace in Mitochondria
503
Mitochondria Are Bounded by a Double Membrane
503
Mitochondria Are the Result of an Endosymbiotic Event 50 4
18.2 Oxidative Phosphorylation Depends o nElectron Transfer
506
The Electron-Transfer Potential of an Electro nIs Measured As Redox Potential
50 6
A 1 .14-Volt Potential Difference Between NADH andMolecular Oxygen Drives Electron Transport Through th eChain and Favors the Formation of a Proton Gradient
50 8
18.3 The Respiratory Chain Consists of Fou rComplexes : Three Proton Pumps and a Physical Lin kto the Citric Acid Cycle
509
The High-Potential Electrons of NADH Enter th eRespiratory Chain at NADH-QOxidoreductase
51 0
Ubiquinol Is the Entry Point for Electrons from FADH 2of Flavoproteins
51 2
Electrons Flow from Ubiquinol to Cytochrome cThrough Q-Cytochrome c Oxidoreductase
51 2
The Q Cycle Funnels Electrons from a Two-ElectronCarrier to a One-Electron Carrier and Pumps Proteins
51 3
Cytochrome c Oxidase Catalyzes the Reductio nof Molecular Oxygen to Water
51 4Toxic Derivatives of Molecular Oxygen Such As Superoxid eRadical Are Scavenged by Protective Enzymes
51 7Electrons Can Be Transferred Between Groups Tha tAre Not in Contact
51 9
The Conformation of Cytochrome c Has Remaine dEssentially Constant for More Than a Billion Years
52 0
18.4 A Proton Gradient Powers the Synthesisof ATP
520
ATP Synthase Is Composed of a Proton-Conductin gUnit and a Catalytic Unit
52 2Proton Flow Through ATP Synthase Leadsto the Release of Tightly Bound ATP :The Binding-Change Mechanism
523
Rotational Catalysis Is the World's SmallestMolecular Motor 524
Proton Flow Around the c Ring Powers ATP Synthesis 52 5
ATP Synthase and G Proteins Have Severa lCommon Features
52 7
18.5 Many Shuttles Allow Movement Across th eMitochondrial Membranes
527
Electrons from Cytoplasmic NADH Ente rMitochondria by Shuttles
52 7
The Entry of ADP into Mitochondria Is Coupledto the Exit of ATP by ATP-ADP Translocase
52 9
Mitochondrial Transporters for Metabolites Hav ea Common Tripartite Structure
53 0
18.6 The Regulation of Cellular RespirationIs Governed Primarily by the Need for ATP
530
The Complete Oxidation of Glucose Yields About 3 0Molecules of ATP
53 1
The Rate of Oxidative Phosphorylation Is Determine dby the Need for ATP 532
Regulated Uncoupling Leads to the Generation of Heat 53 2
Oxidative Phosphorylation Can Be Inhibited atMany Stages
53 3
Mitochondrial Diseases Are Being Discovered
53 4
Mitochondria Play a Key Role in Apoptosis
53 5
Power Transmission by Proton Gradients Is aCentral Motif of Bioenergetics
53 5
Chapter 19 The Light Reactions ofPhotosynthesis
541
Photosynthesis Converts Light Energy int oChemical Energy
54 2
19.1 Photosynthesis Takes Place in Chloroplasts 54 2The Primary Events of Photosynthesis Take Place i nThylakoid Membranes
54 3
Chloroplasts Arose from an Endosymbiotic Event
54 3
19.2 Light Absorption by Chlorophyll Induce sElectron Transfer
544
A Special Pair of Chlorophylls Initiate Charge Separation
54 5
Cyclic Electron Flow Reduces the Cytochrome of theReaction Center
54 7
19.3 Two Photosystems Generate a Proto nGradient and NADPH in OxygenicPhotosynthesis
548
Photosystem II Transfers Electrons from Water t oPlastoquinone and Generates a Proton Gradient
54 8Cytochrome bfLinks Photosystem II to Photosystem I
55 1Photosystem I Uses Light Energy to Generate ReducedFerredoxin, a Powerful Reductant
55 1Ferredoxin-NADP + Reductase Converts NADP +into NADPH
552
19.4 A Proton Gradient Across the Thylakoi dMembrane Drives ATP Synthesis
553
The ATP Synthase of Chloroplasts Closely Resemble sThose of Mitochondria and Prokaryotes
55 4
Cyclic Electron Flow Through Photosystem I Lead sto the Production of ATP Instead of NADPH
55 5
The Absorption of Eight Photons Yields One 02 , TwoNADPH, and Three ATP Molecules
55 6
19.5 Accessory Pigments Funnel Energy intoReaction Centers
557
Resonance Energy Transfer Allows Energy to Movefrom the Site of Initial Absorbance to the Reactio n
Center
55 7
Light-Harvesting Complexes Contain Additiona lChlorophylls and Carotinoids
55 8
The Components of Photosynthesis Are Highl yOrganized
55 9
Many Herbicides Inhibit the Light Reactions o fPhotosynthesis
56 0
19.6 The Ability to Convert Light intoChemical Energy Is Ancient
560
Chapter 20 The Calvin Cycle and thePentose Phosphate Pathway
565
20.1 The Calvin Cycle Synthesizes Hexoses fromCarbon Dioxide and Water
566
Carbon Dioxide Reacts with Ribulose 1,5-bisphosphat eto Form Two Molecules of 3-Phosphoglycerate
56 7
Rubisco Activity Depends on Magnesium and Carbamate 56 8
Rubisco Also Catalyzes a Wasteful Oxygenas eReaction : Catalytic Imperfection
569
Hexose Phosphates Are Made from Phosphoglycerate ,and Ribulose 1,5-bisphosphate Is Regenerated
570
Three ATP and Two NADPH Molecules Are Used toBring Carbon Dioxide to the Level of a Hexose
57 2
Starch and Sucrose Are the Major Carbohydrat eStores in Plants
573
20.2 The Activity of the Calvin Cycl eDepends on Environmental Conditions
574
Rubisco Is Activated by Light-Driven Changes i nProton and Magnesium Ion Concentrations
574
Thioredoxin Plays a Key Role in Regulating th eCalvin Cycle
57 4
The C 4 Pathway of Tropical Plants Accelerate sPhotosynthesis by Concentrating Carbon Dioxide
57 5
Crassulacean Acid Metabolism Permits Growth in Ari dEcosystems
57 7
20.3 The Pentose Phosphate Pathway Generate sNADPH and Synthesizes Five-Carbon Sugars
577
Two Molecules of NADPH Are Generated in th eConversion of Glucose 6-phosphate into Ribulose5-phosphate
57 7
The Pentose Phosphate Pathway and Glycolysis Ar eLinked by Transketolase and Transaldolase
57 9
Mechanism: Transketolase and Transaldolase StabilizeCarbanionic Intermediates by Different Mechanisms
58 1
20.4 The Metabolism of Glucose 6-phosphate bythe Pentose Phosphate Pathway Is Coordinate dwith Glycolysis
58 3
The Rate of the Pentose Phosphate Pathway I sControlled by the Level of NADP +
583
The Flow of Glucose 6-phosphate Depends on theNeed for NADPH, Ribose 5-phosphate, and ATP
58 3
Through the Looking Glass : The Calvin Cycle and th ePentose Phosphate Pathway Are Mirror Images
58 5
20.5 Glucose 6-phosphate Dehydrogenase Playsa Key Role in Protection Against ReactiveOxygen Species
586
A Deficiency of Glucose 6-phosphate Dehydrogenas eCauses a Drug-Induced Hemolytic Anemia
58 6
A Deficiency of Glucose 6-phosphate Dehydrogenas eConfers an Evolutionary Advantage in SomeCircumstances
58 7
Chapter 21 Glycogen Metabolism
592
Glycogen Metabolism Is the Regulated Release an dStorage of Glucose
59 3
21 .1 Glycogen Breakdown Requires the Interplay o fSeveral Enzymes
593
Phosphorylase Catalyzes the Phosphorolytic Cleavageof Glycogen to Release Glucose 1-phosphate
59 4
A Debranching Enzyme Also Is Needed for th eBreakdown of Glycogen
59 4
Phosphoglucomutase Converts Glucose 1-phosphateinto Glucose 6-phosphate
59 5
The Liver Contains Glucose 6-phosphatase, aHydrolytic Enzyme Absent from Muscle
596
Mechanism: Pyridoxal Phosphate Participates in th ePhosphorolytic Cleavage of Glycogen
59 6
21 .2 Phosphorylase Is Regulated by Allosteri cInteractions and Reversible Phosphorylation
598
Muscle Phosphorylase Is Regulated by the Intracellula rEnergy Charge
59 8
Liver Phosphorylase Produces Glucose for Use byOther Tissues
60 0
Phosphorylase Kinase Is Activated by Phosphorylatio nand Calcium Ions
60 0
21 .3 Epinephrine and Glucagon Signal the Nee dfor Glycogen Breakdown
601
G Proteins Transmit the Signal for the Initiation o fGlycogen Breakdown
60 1
Glycogen Breakdown Must Be Rapidly Turned OffWhen Necessary
60 3
The Regulation of Glycogen Phosphorylase BecameMore Sophisticated As the Enzyme Evolved
60 4
21 .4 Glycogen Is Synthesized and Degraded b yDifferent Pathways
604
UDP-Glucose Is an Activated Form of Glucose
60 4
Glycogen Synthase Catalyzes the Transfer of Glucos efrom UDP-Glucose to a Growing Chain
60 5
A Branching Enzyme Forms a-1,6 Linkages
60 6
Glycogen Synthase Is the Key Regulatory Enzyme inGlycogen Synthesis
60 7
Glycogen Is an Efficient Storage Form of Glucose
60 7
21.5 Glycogen Breakdown and Synthesis AreReciprocally Regulated
607
Protein Phosphatase 1 Reverses the Regulatory Effectsof Kinases on Glycogen Metabolism
60 8
Insulin Stimulates Glycogen Synthesis by Activatin gGlycogen Synthase Kinase
61 0
Glycogen Metabolism in the Liver Regulates th eBlood-Glucose Level
61 0
A Biochemical Understanding of Glycogen StorageDiseases Is Possible
61 1
Chapter 22 Fatty Acid Metabolism
617
Fatty Acid Degradation and Synthesis Mirror Eac hOther in Their Chemical Reactions
618
22 .1 Triacylglycerols Are Highly Concentrated
22 .5 Acetyl CoA Carboxylase Plays a Key Rol e
Energy Stores
619
in Controlling Fatty Acid Metabolism
640
Dietary Lipids Are Digested by Pancreatic Lipases
619
Acetyl CoA Carboxylase Is Regulated by Condition s
Dietary Lipids Are Transported in Chylomicrons
620
in the Cell
64 0
Acetyl CoA Carboxylase Is Regulated by a Variety o f
22.2 The Utilization of Fatty Acids as Fuel
Hormones
64 1
Requires Three Stages of Processing
621
22.6 The Elongation and Unsaturation ofTriacylglycerols Are Hydrolyzed by Hormone-
Fatty Acids Are Accomplished by Accessor yStimulated Lipases
621
Enzyme Systems
642Fatty Acids Are Linked to Coenzyme A Before The yAre Oxidized
622
Membrand-Bound Enzymes Generate UnsaturatedFatty Acids
64 2Carnitine Carries Long-Chain Activated Fatty Acid sinto the Mitochondrial Matrix
623
Eicosanoid Hormones Are Derived fromPolyunsaturated Fatty Acids
64 3Acetyl CoA, NADH, and FADH7 Are Generatedin Each Round of Fatty Acid Oxidation
624
The Complete Oxidation of Palmitate Yields 106
Chapter 23 Protein Turnover and Amin oMolecules of ATP
625Acid Catabolism
649
22.3 Unsaturated and Odd-Chain Fatty Acid sRequire Additional Steps for Degradation
626
23.1 Proteins Are Degraded to Amino Acids
650
An Isomerase and a Reductase Are Required for the
The Digestion of Dietary Proteins Begins in th e
Oxidation of Unsaturated Fatty Acids
626
Stomach and Is Completed in the Intestine
650
Odd Chain Fatty Acids Yield Propionyl CoA in
Cellular Proteins Are Degraded at Different Rates
65 1
the Final Thiolysis Step
627
23 .2 Protein Turnover Is Tightly Regulated
651
Vitamin B 17 Contains a Corrin Ring and a Cobalt Ion
628
Ubiquitin Tags Proteins for Destruction
65 1Mechanism : Methylmalonyl CoA Mutase Catalyzes a
The Proteasome Digests the Ubiquitin TaggedRearrangement to Form Succinyl CoA
629
Proteins
65 3Fatty Acids Are Also Oxidized in Peroxisomes
630
Protein Degradation Can Be Used to Regulat eKetone Bodies Are Formed from Acetyl CoA When
Biological Function
65 4Fat Breakdown Predominates
631
The Ubiquitin Pathway and the Proteasome HaveKetone Bodies Are a Major Fuel in Some Tissues
632
Prokaryotic Counterparts
65 5Animals Cannot Convert Fatty Acids into Glucose
63423.3 The First Step in Amino Acid Degradatio n
22.4 Fatty Acids Are Synthesized
Is the Removal of Nitrogen
656
and Degraded by Different Pathways
634
Alpha-Amino Groups Are Converted into Ammoniu m
The Formation of Malonyl CoA Is the Committed
Ions by the Oxidative Deamination of Glutamate
65 6
Step in Fatty Acid Synthesis
635
Mechanism: Pyridoxal Phosphate Forms Schiff-Base
Intermediates in Fatty Acid Synthesis Are Attached
Intermediates in Aminotransferases
65 7
to an Acyl Carrier Protein
635
Aspartate Aminotransferase Is an Archetypa l
Fatty Acid Synthesis Consists of a Series
Pyridoxal-Dependent Transaminase
659
of Condensation, Reduction, Dehydration,
Pyridoxal Phosphate Enzymes Catalyze a Wid eand Reduction Reactions
636
Array of Reactions
65 9
Fatty Acids Are Synthesized by a Multifunctional
Serine and Threonine Can Be Directly Deaminated
66 0Enzyme Complex in Animals
637
Peripheral Tissues Transport Nitrogen to the Liver
66 0The Synthesis of Palmitate Requires 8 Molecule sof Acetyl CoA, 14 Molecules of NADPH,
23 .4 Ammonium Ion Is Converted into Urea i n
and 7 Molecules of ATP
638
Most Terrestrial Vertebrates
66 1
Citrate Carries Acetyl Groups from Mitochondria
The Urea Cycle Begins with the Formatio nto the Cytoplasm for Fatty Acid Synthesis
638
of Carbamoyl Phosphate
661
Several Sources Supply NADPH for Fatty Acid
The Urea Cycle Is Linked to Gluconeogenesis
663Synthesis
639
Urea-Cycle Enzymes Are Evolutionarily Related toFatty Acid Synthase Inhibitors May Be Useful Drugs
640
Enzymes in Other Metabolic Pathways
664
Inherited Defects of the Urea Cycle Cause
Glutamate Is the Precursor of Glutamine, Proline ,Hyperammonemia and Can Lead to Brain Damage
664
and Arginine
68 8
Urea Is Not the Only Means of Disposing of Excess
3-Phosphoglycerate Is the Precursor of Serine ,Nitrogen
666
Cysteine, and Glycine
68 8
23.5 Carbon Atoms of Degraded Amino Acids
Tetrahydrofolate Carries Activated One Carbon Unit sat Several Oxidation Levels
68 9Emerge As Major Metabolic Intermediates
6665-Adenosylmethionine Is the Major Dono r
Pyruvate Is an Entry Point into Metabolism for a
of Methyl Groups
69 1Number of Amino Acids
666
Cysteine Is Synthesized from Serine and Homocysteine 69 3Oxaloacetate Is an Entry Point into Metabolism
High Homocysteine Levels Correlate wit hfor Aspartate and Asparagine
668
Vascular Disease
693Alpha-Ketoglutarate Is an Entry Point into Metabolism
Shikimate and Chorismate Are Intermediates in th efor Five Carbon Amino Acids
668
Biosynthesis of Aromatic Amino Acids
693Succinyl Coenzyme A Is a Point of Entry for Several
Tryptophan Synthase Illustrates Substrate ChannelingNonpolar Amino Acids
668
in Enzymatic Catalysis
696Methionine Degradation Requires the Formation of aKey Methyl Donor, S-Adenosylmethionine
669
24.3 Feedback Inhibition Regulates Amino Aci d
The Branched-Chain Amino Acids Yield Acetyl CoA,
Biosynthesis
697
Acetoacetate, or Propionyl CoA
670
Branched Pathways Require Sophisticated Regulation
69 7Oxygenases Are Required for the Degradation of
An Enzyme Cascade Modulates the ActivityAromatic Amino Acids
671
of Glutamine Synthetase
69 9
23.6 Inborn Errors of Metabolism Can Disrupt
24.4 Amino Acids Are Precursors of ManyAmino Acid Degradation
672
Biomolecules
700
Glutathione, a Gamma-Glutamyl Peptide, Serves Asa Sulfhydryl Buffer and an Antioxidant
70 1Part HI SYNTHESIZING THE MOLECULES
Nitric Oxide, a Short-Lived Signal Molecule, Is FormedOF LIFE
from Arginine
70 2
Porphyrins Are Synthesized from Glycine and Succiny lChapter 24 The Biosynthesis of Amino
Coenzyme A
702
Acids
679
Porphyrins Accumulate in Some Inherited Disorders o fPorphyrin Metabolism
704
Amino Acid Synthesis Requires Solutions to Three KeyBiochemical Problems
68 0
24.1 Nitrogen Fixation: Microorganisms Use
Chapter 25 Nucleotide Biosynthesis
709ATP and a Powerful Reductant to Reduce
Nucleotides Can Be Synthesized by de Novo orAtmospheric Nitrogen to Ammonia
680
Salvage Pathways
71 0The Iron-Molybdenum Cofactor of Nitrogenase Binds
25 .1 In de Novo Synthesis, the Pyrimidin eand Reduces Atmospheric Nitrogen
681
Ring Is Assembled from Bicarbonate ,Ammonium Ion Is Assimilated into an Amino Acid
Aspartate, and Glutamine
710Through Glutamate and Glutamine
683
.2 Amino Acids Are Made from Intermediates
Bicarbonate and Other Oxygenated Carbon Compound s24.2
Activated by Phosphorylation
71 1of the Citric Acid Cycle and Other Major
The Side Chain of Glutamine Can Be HydrolyzedPathways
685
to Generate Ammonia
71 1
Human Beings Can Synthesize Some Amino Acids but
Intermediates Can Move Between Active Site s
Must Obtain Others from the Diet
685
by Channeling
71 1
Aspartate, Alanine, and Glutamate Are Formed by
Orotate Acquires a Ribose Ring from PRP P
the Addition of an Amino Group to an a-Ketoacid
686
to Form a Pyrimidine Nucleotide and Is Converte d
A Common Step Determines the Chirality of All
into Uridylate
71 2
Amino Acids
686
Nucleotide Mono-, Di-, and Triphosphates
The Formation of Asparagine from Aspartate Requires
Are Interconvertible
71 3
an Adenylated Intermediate
687
CTP Is Formed by Amination of UTP
713
25.2 Purine Bases Can Be Synthesized de Nov oor Recycled by Salvage Pathways
714
Salvage Pathways Economize Intracellular EnergyExpenditures
71 4
The Purine Ring System Is Assembled on RibosePhosphate
71 4
The Purine Ring Is Assembled by Successive Steps o fActivation by Phosphorylation Followed by Displacement 71 5
AMP and GMP Are Formed from IMP
71 7
25.3 Deoxyribonucleotides Are Synthesize dby the Reduction of Ribonucleotides Throug ha Radical Mechanism
71 8
Mechanism: A Tyrosyl Radical Is Critical to theAction of Ribonucleotide Reductase
71 8
Thymidylate Is Formed by the Methylation o fDeoxyuridylate
72 0
Dihydrofolate Reductase Catalyzes the Regenerationof Tetrahydrofolate, a One-Carbon Carrier
72 1
Several Valuable Anticancer Drugs Block theSynthesis of Thymidylate
72 2
25.4 Key Steps in Nucleotide Biosynthesis AreRegulated by Feedback Inhibition
723
Pyrimidine Biosynthesis Is Regulated by Aspartat eTranscarbamoylase
72 3
The Synthesis of Purine Nucleotides Is Controlle dby Feedback Inhibition at Several Sites
723
The Synthesis of Deoxyribonucleotides Is Controlledby the Regulation of Ribonucleotide Reductase
72 4
25.5 Disruptions in Nucleotide MetabolismCan Cause Pathological Conditions
725
The Loss of Adenosine Deaminase Activity Resultsin Severe Combined Immunodeficiency
72 5
Gout Is Induced by High Serum Levels of Urate
72 6
Lesch-Nyhan Syndrome Is a Dramatic Consequenceof Mutations in a Salvage-Pathway Enzyme
72 6
Folic Acid Deficiency Promotes Birth Defects Suc hAs Spina Bifida
72 7
Chapter 26 The Biosynthesis of Membran eLipids and Steroids
732
26.1 Phosphatidate Is a Common Intermediatein the Synthesis of Phospholipids an dTriacylglycerols
733
The Synthesis of Phospholipids Requires anActivated Intermediate
73 4
Sphingolipids Are Synthesized from Ceramide
73 6
Gangliosides Are Carbohydrate-Rich Sphingolipid sThat Contain Acidic Sugars
738
Sphingolipids Confer Diversity on Lipid Structur eand Function
73 8
Respiratory Distress Syndrome and Tay-Sachs Diseas eResult from the Disruption of Lipid Metabolism
73 8
26.2 Cholesterol Is Synthesized from Acety lCoenzyme A in Three Stages
739
The Synthesis of Mevalonate, Which Is Activate dAs Isopentenyl Pyrophosphate, Initiates the Synthesi sof Cholesterol
73 9
Squalene (C30 ) Is Synthesized from Six Moleculesof Isopentenyl Pyrophosphate (C 5 )
74 0
Squalene Cyclizes to Form Cholesterol
74 1
26.3 The Complex Regulation of Cholestero lBiosynthesis Takes Place at Several Levels
742
Lipoproteins Transport Cholesterol and TriacylglycerolsThroughout the Organism
74 2
The Blood Levels of Certain Lipoproteins Can Serv eDiagnostic Purposes
74 5
Low-Density Lipoproteins Play a Centrol Rol ein Cholesterol Metabolism
74 5
The LDL Receptor Is a Transmembrane ProteinHaving Five Different Functional Regions
74 6
The Absence of the LDL Receptor Leads toHypercholesteremia and Atherosclerosis
74 7
The Clinical Management of Cholesterol Level sCan Be Understood at a Biochemical Level
74 8
26.4 Important Derivatives of Cholestero lInclude Bile Salts and Steroid Hormones
748
Letters Identify the Steroid Rings and NumbersIdentify the Carbon Atoms
75 0
Steroids Are Hydroxylated by Cytochrome P45 0Monooxygenases That Use NADPH and 02
75 0
The Cytochrome P450 System Is Widespreadand Performs a Protective Function
75 1
Pregnenolone, A Precursor for Many Other Steroids, I sFormed from Cholesterol by Cleavage of Its Side Chain 75 2
Progesterone and Corticosteroids Are Synthesizedfrom Pregnenolone
752
Androgens and Estrogens Are Synthesized fromPregnenolone
753
Vitamin D Is Derived from Cholesterol by
Topoisomerases Prepare the Double Helixthe Ring-Splitting Activity of Light
754
for Unwinding
79 0
Type I Topoisomerases Relax Supercoiled Structures
79 0
Chapter 27 The Integration
Type II Topoisomerases Can Introduce NegativeSupercoils Through Coupling to ATP Hydrolysis
79 1of Metabolism
76028.3 DNA Replication Proceeds by th e
27.1 Metabolism Consists of Highly
Polymerization of Deoxyribonucleosid eInterconnected Pathways
761
Triphosphates Along a Template
793
Recurring Motifs Are Common in Metabolic
DNA Polymerases Require a Template and a Primer
79 3Regulation
761
All DNA Polymerases Have Structural FeaturesMajor Metabolic Pathways Have Specific Control Sites 762
in Common
79 3
Glucose 6-phosphate, Pyruvate, and Acetyl CoA Are
Two Bound Metal Ions Participate inKey Junctions in Metabolism
765
the Polymerase Reaction
79 4
27.2 Each Organ Has a Unique Metabolic
The Specificity of Replication Is Dictated b y
Profile
766
Complementarity of Shape Between Bases
79 4
An RNA Primer Synthesized by Primase Enable s27.3 Food Intake and Starvation Induce
DNA Synthesis to Begin
79 5Metabolic Changes
770
One Strand of DNA Is Made Continuously, Whereas
Metabolic Adaptations in Prolonged Starvation
the Other Strand Is Synthesized in Fragments
79 6
Minimize Protein Degradation
772
DNA Ligase Joins Ends of DNA in Duplex Regions
79 6
Metabolic Derangements in Diabetes Result from
The Separation of DNA Strands Requires Specifi cRelative Insulin Insufficiency and Glucagon Excess
773
Helicases and ATP Hydrolysis
79 7
Caloric Homeostasis Is a Means of Regulatin gBody Weight
774
28.4 DNA Replication Is Highly Coordinated
798
27.4 Fuel Choice During Exercise Is Determined
DNA Replication Requires Highly Processiv ePolymerases
79 8by the Intensity and Duration of Activity
775The Leading and Lagging Strands Are Synthesized in a
27.5 Ethanol Alters Energy Metabolism in
Coordinated Fashion
799
the Liver
777
DNA Replication in Escherichia coli Begins at a
Ethanol Metabolism Leads to an Excess of NADH
777
Unique Site
80 1
Excess Ethanol Consumption Disrupts Vitamin
DNA Synthesis in Eukaryotes Is Initiated
Metabolism
778
at Multiple Sites
80 2
Telomeres Are Unique Structures at the Ends ofLinear Chromosomes
80 3
Chapter 28 DNA Replication, Repair,
Telomeres Are Replicated by Telomerase, a Specialize d
and Recombination
783
Polymerase That Carries Its Own RNA Template
804
28.1 DNA Can Assume a Variety of Structural
28.5 Many Types of DNA Damage
Forms
784
Can Be Repaired
804
The A-DNA Double Helix Is Shorter and Wider Than
Errors Can Occur in DNA Replication
804
the More Common B-DNA Double Helix
784
Some Genetic Diseases Are Caused by the Expansio n
The Major and Minor Grooves Are Lined by Sequence
of Repeats of Three Nucleotides
80 5
Specific Hydrogen-Bonding Groups
785
Bases Can Be Damaged by Oxidizing Agents, Alkylating
Studies of Single Crystals of DNA Revealed Local
Agents, and Light
80 5
Variations in DNA Structure
786
DNA Damage Can Be Detected and Repaire d
Z-DNA Is a Left-Handed Double Helix in Which
by a Variety of Systems
807
Backbone Phosphates Zigzag
787
The Presence of Thymine Instead of Uracil in DNAPermits the Repair of Deaminated Cytosine
80928.2 Double-Stranded DNA Can Wrap Around
Many Cancers Are Caused by the Defectiv eItself to Form Supercoiled Structures
788
Repair of DNA
81 0
The Linking Number of DNA, a Topological Property,
Many Potential Carcinogens Can Be Detected by Their
Determines the Degree of Supercoiling
789
Mutagenic Action on Bacteria
811
28.6 DNA Recombination Plays Important
The Product of RNA Polymerase II, the Pre-mRNARoles in Replication, Repair, and Other
Transcript, Acquires a 5 ' Cap and a 3 ' Poly(A) Tail
84 0
Processes
812
RNA Editing Changes the Proteins Encode dby mRNA
84 2RecA Can Initiate Recombination by Promotin gStrand Invasion
812
Sequences at the Ends of Introns Specify Splice Site sin mRNA Precursors
84 3Some Recombination Reactions Proceed Throug hHolliday Junction Intermediates
813
Splicing Consists of Two Sequential TransesterificationReactions
84 3Some Recombinases Are Evolutionarily Relate dto Topoisomerases
814
Small Nuclear RNAs in Spliceosomes Catalyze th eSplicing of mRNA Precursors
84 4
Transcription and Processing of mRNA Ar eChapter 29 RNA Synthesis and Processing 821
Coupled
84 6
Mutations That Affect Pre-mRNA Splicin gRNA Synthesis Comprises Three Stages : Initiation,
Cause Disease
84 7Elongation, and Termination
822
Most Human Pre-mRNAs Can Be Splice d
29.1 RNA Polymerase Catalyzes Transcription
823
in Alternative Ways to Yield Different Proteins
84 7
RNA Polymerase Binds to Promoter Sites on the DNA
29.4 The Discovery of Catalytic RNA Wa sTemplate to Initiate Transcription
824
Revealing in Regard to Both Mechanism
Sigma Subunits of RNA Polymerase Recognize
and Evolution
848Promoter Sites
82 5
RNA Polymerase Must Unwind the Template Doubl eHelix for Transcription to Take Place
827
Chapter 30 Protein Synthesis
857RNA Chains Are Formed de Novo and Grow inthe 5'-to-3' Direction
827
30 .1 Protein Synthesis Requires the Translatio n
Elongation Takes Place at Transcription Bubbles That
of Nucleotide Sequences into Amino Acid
Move Along the DNA Template
828
Sequences
858
Sequences Within the Newly Transcribed RNA Signal
The Synthesis of Long Proteins Requires a Low Erro rTermination
829
Frequency
85 8
The rho Protein Helps to Terminate the Transcription
Transfer RNA Molecules Have a Common Design
85 9of Some Genes
830
The Activated Amino Acid and the AnticodonSome Antibiotics Inhibit Transcription
831
of tRNA Are at Opposite Ends of the L-Shape d
Precursors of Transfer and Ribosomal RNA Are
Molecule
86 1
Cleaved and Chemically Modified After Transcriptionin Prokaryotes
832
30.2 Aminoacyl-Transfer RNA Synthetases
Read the Genetic Code
86229.2 Transcription in Eukaryotes Is Highly
Amino Acids Are First Activated by Adenylation
86 2Regulated
833Aminoacyl-tRNA Synthetases Have Highly
Three Types of RNA Polymerase Synthesize RNA
Discriminating Amino Acid Activation Sites
86 3
in Eukaryotic Cells
834
Proofreading by Aminoacyl-tRNA SynthetasesThree Common Elements Can Be Found in the RNA
Increases the Fidelity of Protein Synthesis
86 4Polymerase II Promoter Region
836
Synthetases Recognize Various Features of TransferThe TFIID Protein Complex Initiates the Assembly
RNA Molecules
86 5
of the Active Transcription Complex
836
Aminoacyl-tRNA Synthetases Can Be Divided int oMultiple Transcription Factors Interact with Eukaryotic
Two Classes
86 5
Promoters
83 8
Enhancer Sequences Can Stimulate Transcription at
30.3 A Ribosome Is a Ribonucleoprotein
Start Sites Thousands of Bases Away
838
Particle (70S) Made of a Small (305 )and a Large (50S) Subunit
86629.3 The Transcription Products of All ThreeEukaryotic Polymerases Are Processed
839
Ribosomal RNAs (5S, 16S, and 23S rRNA) Playa Central Role in Protein Synthesis
86 7
RNA Polymerase I Produces Three Ribosomal RNAs
839
Proteins Are Synthesized in the Amino-to-Carboxy l
RNA Polymerase III Produces Transfer RNA
840
Direction
869
Messenger RNA Is Translated in the 5 ' -to-3 'Direction
86 9
The Start Signal Is Usually AUG Preceded by SeveralBases That Pair with 16S rRNA
87 0
Bacterial Protein Synthesis Is Initiated b yFormylmethionyl Transfer RNA
87 1
Ribosomes Have Three tRNA- Binding Sites Tha tBridge the 30S and 50S Subunits
87 1
The Growing Polypeptide Chain Is TransferredBetween tRNAs on Peptide-Bond Formation
87 2
Only the Codon-Anticodon Interactions Determin ethe Amino Acid That Is Incorporated
87 3
Some Transfer RNA Molecules Recognize More Tha nOne Codon Because of Wobble in Base-Pairing
87 4
30.4 Protein Factors Play Key Role sin Protein Synthesis
876
Formylmethionyl-tRNA fIs Placed in the P Site o fthe Ribosome in the Formation of the 70S Initiatio nComplex
87 6
Elongation Factors Deliver Aminoacyl-tRNA t othe Ribosome
87 6
The Formation of a Peptide Bond Is Followed b ythe GTP-Driven Translocation of tRNAs and mRNA
87 7
Protein Synthesis Is Terminated by Release Factor s
That Read Stop Codons
87 8
30.5 Eukaryotic Protein Synthesis Differs fro mProkaryotic Protein Synthesis Primarilyin Translation Initiation
879
30.6 Ribosomes Bound to the Endoplasmi cReticulum Manufacture Secretor yand Membrane Proteins
880
Signal Sequences Mark Proteins for Translation Acros s
the Endoplasmic Reticulum Membrane
88 0
Transport Vesicles Carry Cargo Proteins to Their Fina l
Destination
882
30.7 A Variety of Antibiotics and Toxin sCan Inhibit Protein Synthesis
884
Diphtheria Toxin Blocks Protein Synthesi sin Eukaryotes by Inhibiting Translocation
88 5
Ricin Is an N-Glycosidase That Inhibits ProteinSynthesis
88 5
Chapter 31 The Control of GeneExpression
892
31 .1 Many DNA-Binding Proteins Recogniz eSpecific DNA Sequences
893
The Helix-Turn-Helix Motif Is Common to Man yProkaryotic DNA-Binding Proteins
89 4
A Range of DNA-Binding Structures Are Employed b yEukaryotic DNA-Binding Proteins
89 5
31 .2 Prokaryotic DNA-Binding Proteins Bin dSpecifically to Regulatory Sites in Operons
896
An Operon Consists of Regulatory Elements an dProtein-Encoding Genes
89 7
The lac Repressor Protein in the Absence of Lactos eBinds to the Operator and Blocks Transcription
89 7
Ligand Binding Can Induce Structural Changes i nRegulatory Proteins
89 8
The Operon Is a Common Regulatory Unit in Prokaryotes 89 9
Transcription Can Be Stimulated by Proteins Tha tContact RNA Polymerase
90 0
31.3 The Greater Complexity of Eukaryoti cGenomes Requires Elaborate Mechanisms fo rGene Regulation
901
Multiple Transcription Factors Interact with Eukaryoti cRegulatory Sites
90 2
Eukaryotic Transcription Factors Are Modular
90 2
Activation Domains Interact with Other Proteins
90 2
Nucleosomes Are Complexes of DNA and Histones
90 3
Eukaryotic DNA Is Wrapped Around Histones to FormNucleosomes
90 4
The Control of Gene Expression Can RequireChromatin Remodeling
90 5
Enhancers Can Stimulate Transcription in Specifi cCell Types
90 6
The Methylation of DNA Can Alter Patterns of Gen eExpression
90 7
Steroids and Related Hydrophobic Molecules Pas sThrough Membranes and Bind to DNA-Bindin gReceptors
90 7
Nuclear Hormone Receptors Regulate Transcriptio nby Recruiting Coactivators to the Transcription Complex
90 9
Steroid-Hormone Receptors Are Targets for Drugs
910
Chromatin Structure Is Modulated Through Covalent
Rearrangements in the Genes for the Green and Re dModifications of Histone Tails
910
Pigments Lead to "Color Blindness"
93 6
Histone Deacetylases Contribute to Transcriptional
32 .4 Hearing Depends on the Speed yRepression
912Detection of Mechanical Stimuli
93731 .4 Gene Expression Can Be Controlled at
Hair Cells Use a Connected Bundle of StereociliaPosttranscriptional Levels
913
to Detect Tiny Motions
93 7
Attenuation Is a Prokaryotic Mechanism for
Mechanosensory Channels Have Been Identifie dRegulating Transcription Through the Modulation
in Drosophilia and Vertebrates
93 9of Nascent RNA Secondary Structure
91 3
Genes Associated with Iron Metabolism Are
32 .5 Touch Includes the Sensing of Pressure,
Translationally Regulated in Animals
914
Temperature, and Other Factors
939
Studies of Capsaicin Reveal a Receptor for Sensin gHigh Temperatures and Other Painful Stimuli
94 0
Part IV RESPONDING TO
More Sensory Systems Remain to be Studied
94 1
ENVIRONMENTAL CHANGE S
Chapter 32 Sensory Systems
921 Chapter 33 The Immune System
945
32 .1 A Wide Variety of Organic Compounds
Innate Immunity Is an Evolutionarily Ancien t
Are Detected by Olfaction
922
Defense System
94 6
The Adaptive Immune System Responds by Usin gOlfaction Is Mediated by an Enormous Family
the Principles of Evolution
94 7of Seven-Transmembrane-Helix Receptors
92 3
Odorants Are Decoded by a Combinatorial
33 .1 Antibodies Possess Distinct Antigen-Binding
Mechanism
924
and Effector Units
949
Functional Magnetic Resonance Imaging Reveals
33.2 The Immunoglobulin Fold ConsistsRegions of the Brain Processing Sensory Information
925
of a Beta-Sandwich Framework wit h
32.2 Taste Is a Combination of Senses That
Hypervariable Loops
952
Function by Different Mechanisms
926
33.3 Antibodies Bind Specific Molecule s
Sequencing of the Human Genome Led to the
Through Their Hypervariable Loops
953
Discovery of a Large Family of 7TM Bitter Receptors
927
X-ray Analyses Have Revealed How Antibodies BindA Heterodimeric 7TM Receptor Responds to Sweet
Antigens
95 3Compounds
929
Large Antigens Bind Antibodies with NumerousUmami, the Taste of Glutamate and Aspartate,
Interactions
95 4Is Mediated by a Heterodimeric Receptor Relatedto the Sweet Receptor
930
33 .4 Diversity Is Generated by Gene
Salty Tastes Are Detected Primarily by the Passage
Rearrangements
956
of Sodium Ions Through Channels
930
J (Joining) Genes and D (Diversity) Genes Increas e
Sour Tastes Arise from the Effects of Hydrogen Ions
Antibody Diversity
95 6
(Acids) on Channels
931
More Than 108 Antibodies Can Be Formed b y
32.3 Photoreceptor Molecules in the Eye
Combinatorial Association and Somatic Mutation
95 8
The Oligomerization of Antibodies ExpressedDetect Visible Light
931
on the Surfaces of Immature B Cells Triggers AntibodyRhodopsin, a Specialized 7TM Receptor, Absorbs
Secretion
95 8Visible Light
932
Different Classes of Antibodies Are Formed by th eLight Absorption Induces a Specific Isomerization
Hopping of VH Genes
96 0of Bound 11-cis-Retinal
93 3
Light Induced Lowering of the Calcium Level
33.5 Major-Histocompatibility-Complex Protein s
Coordinates Recovery
934
Present Peptide Antigens on Cell Surfaces fo r
Color Vision Is Mediated by Three Cone
Recognition by T-Cell Receptors
961
Receptors That Are Homologs of
Peptides Presented by MHC Proteins Occupy aRhodopsin
935
Deep Groove Flanked by Alpha Helices
962
T-Cell Receptors Are Antibody-like ProteinsContaining Variable and Constant Regions
96 3
CD8 on Cytotoxic T Cells Acts in Concer twith T-Cell Receptors
96 4
Helper T Cells Stimulate Cells That Display Foreig nPeptides Bound to Class II MHC Proteins
96 5
Helper T Cells Rely on the T-Cell Receptorand CD4 to Recognize Foreign Peptides o nAntigen-Presenting Cells
96 6
MHC Proteins Are Highly Diverse
96 8
Human Immunodeficiency Viruses Subvertthe Immune System by Destroying Helper T Cells
96 9
33.6 Immune Responses Against Self-Antigen sAre Suppressed
970
T Cells Are Subjected to Positive and NegativeSelection in the Thymus
97 0
Autoimmune Diseases Results from the Generation o fImmune Responses Against Self-Antigens
97 1
The Immune System Plays a Role in Cance rPrevention
97 1
Chapter 34 Molecular Motors
977
34.1 Most Molecular-Motor Proteins Ar eMembers of the P-Loop NTPase Superfamily
978
A Motor Protein Consists of an ATPase Core and a nExtended Structure
978
ATP Binding and Hydrolysis Induce Changes in theConformation and Binding Affinity of Moto rProteins
980
34.2 Myosins Move Along Actin Filaments
982
Muscle Is a Complex of Myosin and Actin
982
Actin Is a Polar, Self-Assembling, DynamicPolymer
98 5
Motions of Single Motor Proteins Can Be Directl yObserved
986
Phosphate Release Triggers the Myosin Power Stroke
98 7
The Length of the Lever Arm Determines Moto rVelocity
988
34.3 Kinesin and Dynein Move AlongMicrotubules
989
Microtubules Are Hollow Cylindrical Polymers
989
Kinesin Motion Is Highly Processive
99 1
34.4 A Rotary Motor Drives Bacterial Motion
993
Bacteria Swim by Rotating Their Flagella
993
Proton Flow Drives Bacterial Flagellar Rotation
99 4
Bacterial Chemotaxis Depends on Reversal of theDirection of Flagellar Rotation
995
Chapter 35 Drug Development
1001
35 .1 The Development of Drugs Presents HugeChallenges
1002
Drug Candidates Must Be Potent Modulators of TheirTargets
100 2
Drugs Must Have Suitable Properties to Reac hTheir Targets
100 3
Toxicity Can Limit Drug Effectiveness
100 8
35.2 Drug Candidates Can Be Discovered bySerendipity, Screening, or Design
1009
Serendipitous Observations Can Drive Dru gDevelopment
100 9
Screening Libraries of Compounds Can Yield Drugs o rDrug Leads
101 1
Drugs Can Be Designed on the Basis of Three -Dimensional Structural Information Abou tTheir Targets
101 4
35.3 The Analysis of Genomes Holds Grea tPromise for Drug Discovery
1017
Potential Targets Can Be Identified in the Huma nProteome
101 7
Animal Models Can Be Developed to Test the Validityof Potential Drug Targets
101 8
Potential Targets Can Be Identified in the Genomesof Pathogens
101 8
Genetic Differences Influence Individual Response sto Drugs
101 9
35.4 The Development of Drugs Proceed sThrough Several Stages
1020
Clinical Trials Are Time Consuming and Expensive
102 0
The Evolution of Drug Resistance Can Limit th eUtility of Drugs for Infectious Agents and Cancer
102 1
Appendices
Al
Glossary of Compounds
B l
Answers to Problems
ClIndex
Dl
