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biochemi str y
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Reginald H. Garrett | Charles M. Grisham

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Reginald H. Garrett, Charles M. Grisham
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About the Authors
Reginald H. Garrett was educated in the Baltimore city public Charles M. Grisham was born and raised in Minneapolis,
schools and at the Johns Hopkins University, where he earned his Minnesota, and educated at Benilde High School. He received
Ph.D. in biology in 1968. Since then, he has been at the University his B.S. in chemistry from the Illinois Institute of Technology in
of Virginia, where he is a Professor Emeritus of Biology. He is the 1969 and his Ph.D. in chemistry from the University of Minne-
author of previous editions of Biochemistry as well as Principles sota in 1973. Following a postdoctoral appointment at the Insti-
of Biochemistry (Cengage, Brooks/Cole) and numerous papers tute for Cancer Research in Philadelphia, he joined the faculty
and review articles on the biochemical, genetic, and molecular of the University of Virginia, where he is Professor of Chemis-
biological aspects of inorganic nitrogen metabolism. His research try. He is the author of previous editions of Biochemistry and
interests focused on the pathway of nitrate assimilation in Principles of Biochemistry (Cengage, Brooks/Cole) and numer-
filamentous fungi. His investigations contributed substantially ous papers and review articles on active transport of sodium,
to our understanding of the enzymology, genetics, and regula- potassium, and calcium in mammalian systems, on protein
tion of this major pathway of biological nitrogen acquisition. kinase C, and on the applications of NMR and EPR spectros-
More recently, he has collaborated in systems approaches to the copy to the study of biological systems. He also authored Inter-
metabolic basis of nutrition-related diseases. His research active Biochemistry CD-ROM and Workbook, a tutorial CD for
has been supported by the National Institutes of Health, the students. His work has been supported by the National Insti-
National Science Foundation, and private industry. He is a tutes of Health, the National Science Foundation, the Muscular
former Fulbright Scholar at the Universität für Bodenkultur in Dystrophy Association of America, the Research Corporation,
Vienna, Austria and served as Visiting Scholar at the University the American Heart Association, and the American Chemical
of Cambridge on two separate occasions. During the second, he Society. He is a Research Career Development Awardee of the
was the Thomas Jefferson Visiting Fellow in Downing College. National Institutes of Health, and in 1983 and 1984 he was a
In 2003, he was Professeur Invité at the Université Paul Sabatier/ Visiting Scientist at the Aarhus University Institute of Physiol-
Toulouse III and the Centre National de la Recherche ogy Denmark. In 1999, he was Knapp Professor of Chemistry at
Scientifique, Institute for Pharmacology and Structural Biology the University of San Diego. He has taught biochemistry, intro-
in France. He taught biochemistry at the University of Virginia ductory chemistry, and physical chemistry at the University of
for 46 years. He is a member of the American Society for Virginia for 48 years. He is a member of the American Society
Biochemistry and Molecular Biology. for Biochemistry and Molecular Biology.
Gene Runion
Reginald H. Garrett and Charles M. Grisham

iv
Contents in Brief
Part I Molecular Components of Cells 1

1 The Facts of Life: Chemistry Is the Logic of Biological Phenomena 1
2 Water: The Medium of Life 29
3 Thermodynamics of Biological Systems 51
4 Amino Acids and the Peptide Bond 77
5 Proteins: Their Primary Structure and Biological Functions 105
6 Proteins: Secondary, Tertiary, and Quaternary Structure 145
7 Carbohydrates and the Glycoconjugates of Cell Surfaces 193
8 Lipids 237
9 Membranes and Membrane Transport 265
10 Nucleotides and Nucleic Acids 317
11 Structure of Nucleic Acids 345
12 Recombinant DNA, Cloning, Gene Editing, and Synthetic Biology—An Introduction 393
Part II Protein Dynamics 433

13 Enzymes—Kinetics and Specificity 433
14 Mechanisms of Enzyme Action 475
15 Enzyme Regulation 511
16 Molecular Motors 543
Part III Metabolism and Its Regulation 573

17 Metabolism: An Overview 573
18 Glycolysis 603
19 The Tricarboxylic Acid Cycle 635
20 Electron Transport and Oxidative Phosphorylation 671
21 Photosynthesis 713
22 Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway 751
23 Fatty Acid Catabolism 791
24 Lipid Biosynthesis 821
25 Nitrogen Acquisition and Amino Acid Metabolism 871
26 Synthesis and Degradation of Nucleotides 921
27 Metabolic Integration and Organ Specialization 951
Part IV Information Transfer 981

28 DNA Metabolism: Replication, Recombination, and Repair 981
29 Transcription and the Regulation of Gene Expression 1033
30 Protein Synthesis 1089
31 Completing the Protein Life Cycle: Folding, Processing, and Degradation 1131
32 The Reception and Transmission of Extracellular Information 1161
Abbreviated Answers to Problems A-1

Index I-1
v
Detailed Contents
Part I Molecular Components of Cells 1 eak Forces Restrict Organisms to a Narrow Range
W
of Environmental Conditions 16
1
Enzymes Catalyze Metabolic Reactions 17
Biomolecular Phenomena across the Time Scale of Life 17
1.5 What Are the Organization and Structure of
The Facts of Life: Chemistry Is the Logic of Cells? 17
The Eukaryotic Cell Likely Emerged from an Archaeal
Biological Phenomena 1 Lineage 18
1.1 What Are the Distinctive Properties of Living How Many Genes Does a Cell Need? 18
Systems? 1 Critical Developments in Biochemistry: Synthetic Life 19
1.2 What Kinds of Molecules Are Biomolecules? 4 Archaea and Bacteria Have a Relatively Simple
Biomolecules Are Carbon Compounds 5 Structural Organization 20
1.3 What Is the Structural Organization of Complex The Structural Organization of Eukaryotic Cells Is More
Biomolecules? 5 Complex Than That of Prokaryotic Cells 21
etabolites Are Used to Form the Building Blocks
M 1.6 What Are Viruses? 22
of Macromolecules 5 Foundational Biochemistry 25
Organelles Represent a Higher Order in Biomolecular Problems 25
Organization 8
Further Reading 27
Membranes Are Supramolecular Assemblies That Define
2
the Boundaries of Cells 9
The Unit of Life Is the Cell 9
1.4 How Do the Properties of Biomolecules Reflect Their
Fitness to the Living Condition? 10
Water: The Medium of Life 29
iological Macromolecules and Their Building Blocks
B
Have a “Sense” or Directionality 10 2.1 What Are the Properties of Water? 29
Biological Macromolecules Are Informational 11 Water Has Unusual Properties 30
Biomolecules Have Characteristic Hydrogen Bonding in Water Is Key to Its Properties 30
Three-Dimensional Architecture 12 The Structure of Ice Is Based on H-Bond
Weak Forces Maintain Biological Structure and Formation 30
Determine Biomolecular Interactions 12 Molecular Interactions in Liquid Water Are Based on
Van der Waals Forces Are Short-Range Interactions H Bonds 31
between Atoms in Nearby Molecules 12 The Solvent Properties of Water Derive from Its Polar
Hydrogen Bonds Form between H Atoms and Nature 32
Electronegative Atoms Like N and O 14 Water Can Ionize to Form H1 and OH2 36
Ionic Interactions Form between Oppositely Charged 2.2 What Is pH? 37
Groups or Molecules 14
Strong Electrolytes Dissociate Completely in Water 38
Hydrophobic Interactions Are the Result of Favorable
Weak Electrolytes Are Substances That Dissociate
Interactions between Water Molecules 14
Only Slightly in Water 39
The Defining Concept of Biochemistry Is
The Henderson–Hasselbalch Equation Describes the
“Molecular Recognition through Structural
Dissociation of a Weak Acid in the Presence of Its
Complementarity” 14
Conjugate Base 39
Biomolecular Recognition Is Mediated by Weak Chemical
Forces 15
vi
Detailed Contents vii
itration Curves Illustrate the Progressive

T tandard Reduction Potentials Are Measured
S
Dissociation of a Weak Acid 41 in Reaction Half-Cells 66
Phosphoric Acid Has Three Dissociable H1 42 %o9 Values Can Be Used to Predict the Direction
2.3 What Are Buffers, and What Do They Do? 43 of Redox Reactions 67
he Phosphate Buffer System Is a Major Intracellular
T %o9 Values Can Be Used to Analyze Energy Changes
Buffering System 43 in Redox Reactions 67
The Imidazole Group of Histidine Also Serves The Reduction Potential Depends on Concentration 69
as an Intracellular Buffering System 44 3.7 Why Are Coupled Processes Important to Living
The Bicarbonate Buffer System of Blood Plasma 44 Things? 69
Buffers Useful within Physiological pH Ranges 45 A Deeper Look: Coupling a Reaction to ATP Hydrolysis
Human Biochemistry: Blood pH and Respiration 46 Changes Its Keq by a Factor of 108 71
2.4 What Properties of Water Give It a Unique 3.8 What Is the Daily Human Requirement for ATP? 71
Role in the Environment? 46 Foundational Biochemistry 72
Foundational Biochemistry 47 Problems 73
Problems 47 Further Reading 75
Further Reading 49
3 4
Amino Acids and the Peptide Bond 77
Thermodynamics of Biological Systems 51 4.1 What Are the Structures and Properties of Amino Acids? 77
3.1 What Are the Basic Concepts of Thermodynamics? 51 Typical Amino Acids Contain a Central Tetrahedral
hree Quantities Describe the Energetics
T Carbon Atom 77
of Biochemical Reactions 52 Amino Acids Can Join via Peptide Bonds 78
All Reactions and Processes Follow There Are 20 Common Amino Acids 78
the Laws of Thermodynamics 53 Are There Other Ways to Classify Amino Acids? 82
A Deeper Look: Entropy, Information, and the A Deeper Look: Why Nature Chose Selenium 82
Importance of “Negentropy” 54 Amino Acids 21 and 22—and More? 83
Free Energy Provides a Simple Criterion for Equilibrium 54 Several Amino Acids Occur Only Rarely in Proteins 83
3.2 What Is the Effect of Concentration on Net 4.2 What Are the Acid–Base Properties of Amino Acids? 83
Free Energy Changes? 55 Amino Acids Are Weak Polyprotic Acids 83
3.3 How May Standard State, Equilibrium, and Cellular Critical Developments in Biochemistry: Adding New
Conditions Be Compared? 56 Chemistry to Proteins with Unnatural Amino Acids 84
3.4 What Are the Characteristics of High-Energy Side Chains of Amino Acids Undergo Characteristic
Biomolecules? 57 Ionizations 86
High Energy Phosphate Compounds 58 4.3 What Reactions Do Amino Acids Undergo? 89
A Deeper Look: Why Nature Chose Phosphates 59 4.4 What Are the Optical and Stereochemical Properties
ATP Is an Intermediate Energy-Shuttle Molecule 59 of Amino Acids? 89
The Hydrolysis of Phosphoric Acid Anhydrides Amino Acids Are Chiral Molecules 89
Is Highly Favorable 60 Chiral Molecules Are Described by the d,l and (R,S)
The Hydrolysis DG° of ATP and ADP Is Greater Than Naming Conventions 90
That of AMP 61 Critical Developments in Biochemistry: Green
Acetyl Phosphate and 1,3-Bisphosphoglycerate Fluorescent Protein—The “Light Fantastic”—from
Are Phosphoric-Carboxylic Anhydrides 61 Jellyfish to Gene Expression 91
Enol Phosphates Are Potent Phosphorylating Agents 62 4.5 What Are the Spectroscopic Properties of Amino
The Complex Equilibria Involved in ATP Hydrolysis 64 Acids? 91
3.5 How Do Group Transfer Potentials Quantify the henylalanine, Tyrosine, and Tryptophan
P
Reactivity of Functional Groups? 65 Absorb Ultraviolet Light 92
3.6 What Are Reduction Potentials, and How Are They Amino Acids Can Be Characterized by Nuclear Magnetic
Resonance 92
Used to Account for Free Energy Changes in Redox
Reactions? 66 Critical Developments in Biochemistry: Rules for
Description of Chiral Centers in the (R,S) System 93
viii Detailed Contents
4.6 How Are Amino Acid Mixtures Step 6. Reconstruction of the Overall Amino Acid
Separated and Analyzed? 94 Sequence 120
Amino Acids Can Be Separated by Chromatography 94 The Amino Acid Sequence of a Protein Can Be
Determined by Mass Spectrometry 122
4.7 What Is the Fundamental Structural
Pattern in Proteins? 94 Sequence Databases Contain the Amino Acid Sequences
of Millions of Different Proteins 125
The Peptide Bond Has Partial Double-Bond Character 95
The Polypeptide Backbone Is Relatively Polar 97 5.4 What Is the Nature of Amino Acid Sequences? 126
Peptides Can Be Classified According to How Many omologous Proteins from Different Organisms Have
H
Amino Acids They Contain 97 Homologous Amino Acid Sequences 127
The Amino Acids in Polypeptides Can Be Released Computer Programs Can Align Sequences and Discover
by Acid Hydrolysis 98 Homology between Proteins 127
Proteins Are Composed of One or More Polypeptide Related Proteins Share a Common Evolutionary
Chains 98 Origin 130
Apparently Different Proteins May Share a Common
Foundational Biochemistry 100
Ancestry 131
Problems 101
A Mutant Protein Is a Protein with a Slightly Different
Further Reading 103 Amino Acid Sequence 131
5.5 How Are Polypeptides Synthesized
5 in the Laboratory? 131

Orthogonal Synthesis of Peptides 132
Solid-Phase Methods Are Very Useful in Peptide
Proteins: Their Primary Structure and Biological Synthesis 132
Functions 105 5.6 Do Proteins Have Chemical Groups Other Than
5.1 What Architectural Arrangements Amino Acids? 132
Characterize Protein Structure? 105 5.7 What Are the Many Biological Functions of
roteins Fall into Three Basic Classes According to Shape
P Proteins? 134
and Solubility 106 Proteins Are the Agents of Biological Function 135
Protein Structure Is Described in Terms of Four Levels of All Proteins Function through Specific Recognition and
Organization 107 Binding of Some Target Molecule 135
Noncovalent Forces Drive Formation of the Higher 5.8 What Is the Proteome and What Does It Tell Us? 137
Orders of Protein Structure 109
The Proteome Is Large and Dynamic 137
A Protein’s Conformation Can Be Described as Its Overall
Determining the Proteome of a Cell 137
Three-Dimensional Structure 109
Critical Developments in Biochemistry: Two New Suffixes
5.2 How Are Proteins Isolated and Purified from in Molecular Biology and Biochemistry: “-ome” and
Cells? 110 “-omics” 138
Number of Protein Separation Methods Exploit
A A Deeper Look: The Human Proteome Project and the
Differences in Size and Charge 110 Human Protein Atlas 139
A Deeper Look: Estimation of Protein Concentrations in Foundational Biochemistry 139
Solutions of Biological Origin 111
Problems 140
A Typical Protein Purification Scheme Uses a Series of
Separation Methods 111 Further Reading 142
A Deeper Look: Techniques Used in Protein
5.3
Purification 112
How Is the Primary Structure of a Protein
Determined? 115
6
Sanger Was the First to Determine the Sequence of a Proteins: Secondary, Tertiary, and Quaternary
Protein 116 Structure 145
Both Chemical and Enzymatic Methodologies Are Used 6.1 What Noncovalent Interactions Stabilize the Higher
in Protein Sequencing 116
Levels of Protein Structure? 146
Step 1. Separation of Polypeptide Chains 116
Hydrogen Bonds Are Formed Whenever Possible 146
A Deeper Look: The Virtually Limitless Number of
Hydrophobic Interactions Drive Protein Folding 146
Different Amino Acid Sequences 117
Ionic Interactions Usually Occur on the Protein
Step 2. Cleavage of Disulfide Bridges 117
Surface 147
Step 3. N- and C-Terminal Analysis 117
Van der Waals Interactions Are Ubiquitous 147
Steps 4 and 5. Fragmentation of the Polypeptide Chain 119
Detailed Contents ix
6.2 What Role Does the Amino Acid Sequence Play rtificial Intelligence Algorithms Predict Protein
A
in Protein Structure? 147 Structures Accurately 180
6.3 What Are the Elements of Secondary Structure in Critical Developments in Biochemistry: NMR and
Proteins, and How Are They Formed? 148 Cryo-EM — Revolutionary Methods that Probe Protein
Structure and Dynamics 180
he Amide Plane Is a Fundamental Determinant of
T
All Protein Structure 148 6.5 How Do Protein Subunits Interact at the Quaternary
The Alpha-Helix Is a Key Secondary Structure 150 Level of Protein Structure? 181
A Deeper Look: Knowing What the Right Hand and Left Human Biochemistry: Diseases of Protein Folding 182
Hand Are Doing 150 Human Biochemistry: Structural Genomics 183
Critical Developments in Biochemistry: X-ray There Is Symmetry in Quaternary Structures 183
Crystallography of Proteins 151 Quaternary Association Is Driven by Weak Forces 183
The b-Pleated Sheet Is a Core Structure in Proteins 153 Open Quaternary Structures Can Polymerize 185
Critical Developments in Biochemistry: In Bed with a There Are Structural and Functional Advantages to
Cold, Pauling Stumbles onto the α-Helix and a Nobel Quaternary Association 185
Prize 154 Human Biochemistry: Faster-Acting Insulin: Genetic
Helix–Sheet Composites Provide Flexibility and Engineering Solves a Quaternary Structure Problem 186
Strength in Spider Silk 156 Foundational Biochemistry 188
b-Turns Allow the Protein Strand to Change Direction 156
Problems 188
6.4 How Do Polypeptides Fold into Three-Dimensional Further Reading 190
Protein Structures? 157
7
A Deeper Look: The Coiled-Coil Motif in Proteins 158
Fibrous Proteins Usually Play a Structural Role 159
Globular Proteins Mediate Cellular Function 162
Helices and Sheets Make Up the Core of Most Globular Carbohydrates and the Glycoconjugates of Cell
Proteins 162
Critical Developments in Biochemistry: The Protein Data
Surfaces 193
Bank (PDB) 162 7.1 How Are Carbohydrates Named? 194
Water Molecules on the Protein Surface Stabilize the 7.2 What Are the Structure and Chemistry
Structure 163 of Monosaccharides? 194
Packing Considerations 163 Monosaccharides Are Classified as Aldoses and
Human Biochemistry: Collagen-Related Diseases 164 Ketoses 194
Protein Domains Are Nature’s Modular Strategy for Stereochemistry Is a Prominent Feature of
Protein Design 165 Monosaccharides 195
Denaturation Leads to Loss of Protein Structure and Monosaccharides Exist in Cyclic and Anomeric Forms 197
Function 165 Haworth Projections Are a Convenient Device for
Human Biochemistry: Domain-Based Engineering Drawing Sugars 198
of Proteins Forms the Basis of a Novel Cancer Monosaccharides Can Be Converted to Several Derivative
Treatment 167 Forms 200
Anfinsen’s Classic Experiment Proved That Sequence A Deeper Look: Honey—An Ancestral Carbohydrate
Determines Structure 169 Treat 202
Is There a Single Mechanism for Protein Folding? 169
7.3 What Are the Structure and Chemistry
What Is the Thermodynamic Driving Force for Protein of Oligosaccharides? 204
Folding? 172
Disaccharides Are the Simplest Oligosaccharides 204
Marginal Stability of the Tertiary Structure Makes Proteins
A Deeper Look: Trehalose—A Natural Protectant for
Flexible 172
Bugs 205
Motion in Globular Proteins 172
A Variety of Higher Oligosaccharides Occur in
The Folding Tendencies and Patterns of Globular Nature 206
Proteins 173
Human Biochemistry: Alpha-Gal and Red Meat
A Deeper Look: Metamorphic Proteins—A Consequence Allergy 207
of Dynamism and Marginal Stability 175
7.4 What Are the Structure and Chemistry
Proteins Can Be Classified on the Basis of Folding
Patterns 176 of Polysaccharides? 208
Molecular Chaperones Are Proteins That Help Other omenclature for Polysaccharides Is Based on Their
N
Proteins to Fold 177 Composition and Structure 208
Some Proteins Are Intrinsically Unstructured 178 Polysaccharides Serve Energy Storage, Structure, and
Protection Functions 209
x Detailed Contents
Polysaccharides Provide Stores of Energy 209 8.3 What Are the Structures and Chemistry
Polysaccharides Provide Physical Structure and Strength of Glycerophospholipids? 242
to Organisms 210 Glycerophospholipids Are the Most Common
A Deeper Look: Ruth Benerito and Wrinkle-Free Cotton Phospholipids 243
Fabrics 213 Ether Glycerophospholipids Include PAF and
Polysaccharides Provide Strength and Rigidity to Bacterial Plasmalogens 245
Cell Walls 214 Human Biochemistry: Platelet-Activating Factor: A
A Deeper Look: A Complex Polysaccharide in Red Potent Ether Glycerophospholipid Mediator 246
Wine—The Strange Story of Rhamnogalacturonan II 215 8.4 What Are Sphingolipids, and How Are They Important
Animals Display a Variety of Cell Surface for Higher Animals? 246
Polysaccharides 218
8.5 What Are Waxes, and How Are They Used? 246
7.5 What Are Glycoproteins, and How Do They Function A Deeper Look: Novel Lipids with Valuable
in Cells? 218 Properties 248
Carbohydrates on Proteins Can Be O-Linked or
8.6 What Are Terpenes, and What Is Their Relevance
N-Linked 218
to Biological Systems? 249
O-GlcNAc Signaling Is Altered in Diabetes and
A Deeper Look: Why Do Plants Emit Isoprene? 251
Cancer 220
Human Biochemistry: Coumadin or Warfarin—Agent of
O-Linked Saccharides Form Rigid Extended Extracellular
Life or Death 251
Structures 220
Polar Fish Depend on Antifreeze Glycoproteins 220 8.7 What Are Steroids, and What Are Their Cellular
N-Linked Oligosaccharides Can Affect the Physical Functions? 252
Properties and Functions of a Protein 221 Cholesterol 252
Human Biochemistry: Drug Research Finds a Sweet Steroid Hormones Are Derived from Cholesterol 252
Spot 222 Human Biochemistry: Plant Sterols and Stanols—
Sialic Acid Terminates the Oligosaccharides of Natural Cholesterol Fighters 254
Glycoproteins and Glycolipids 222 8.8 How Do Lipid Metabolites Act
Sialic Acid Cleavage Can Serve as a Timing Device for as Biological Signals? 254
Protein Degradation 223 Human Biochemistry: Beating COVID-19: Lipid
7.6 How Do Proteoglycans Modulate Processes Nanoparticles Make RNA Vaccines Practical and
in Cells and Organisms? 224 Effective 255
Functions of Proteoglycans Involve Binding to Other Human Biochemistry: The Endocannabinoid
Proteins 225 Signaling System: A Target for Next-Generation
Proteoglycans May Modulate Cell Growth Processes 226 Therapeutics 256
Proteoglycans Make Cartilage Flexible and Resilient 226 Human Biochemistry: Fingolimod—a Sphingosine-1-P
Mimic Is an Oral Drug for Multiple Sclerosis 258
7.7 How Do Carbohydrates Provide a Structural
Code? 226 8.9 What Can Lipidomics Tell Us about Cell, Tissue,
and Organ Physiology? 259
Lectins Translate the Sugar Code 228
Selectins, Rolling Leukocytes, and the Inflammatory
Response 228 Problems 261
Galectins—Mediators of Inflammation, Immunity, and Further Reading 263
Cancer 229
Problems 231
Further Reading 234
9
Membranes and Membrane Transport 265
8 9.1 What Are the Chemical and Physical

Properties of Membranes? 266
The Composition of Membranes Suits Their
Lipids 237 Functions 266
Lipids Form Ordered Structures Spontaneously in
8.1 What Are the Structures and Chemistry of Fatty
Water 267
Acids? 237
The Fluid Mosaic Model Describes Membrane
8.2 What Are the Structures and Chemistry Dynamics 269
of Triacylglycerols? 241
9.2 What Are the Structure and Chemistry of Membrane
A Deeper Look: Polar Bears Prefer Nonpolar Food 242
Proteins? 271
Detailed Contents xi
eripheral Membrane Proteins Associate Loosely

P 10.2 What Are Nucleosides? 319
with the Membrane 271 Human Biochemistry: Adenosine: A Nucleoside
Integral Membrane Proteins Are Firmly Anchored with Physiological Activity 320
in the Membrane 271 10.3 What Are the Structure and Chemistry
Lipid-Anchored Membrane Proteins Can Act as Switching of Nucleotides? 320
Devices 280
Cyclic Nucleotides Are Cyclic Phosphodiesters 322
9.3 How Are Biological Membranes Organized? 282 Nucleoside Diphosphates and Triphosphates Are
9.4 What Are the Dynamic Processes Nucleotides with Two or Three Phosphate Groups 322
That Modulate Membrane Function? 283 Human Biochemistry: cGAMP, a Cyclic Dinucleotide
L ipids and Proteins Undergo a Variety That Triggers a Response to Infection 322
of Movements in Membranes 283 NDPs and NTPs Are Polyprotic Acids 323
Membrane Lipids Can Be Ordered to Different Nucleoside 59-Triphosphates Are Carriers of Chemical
Extents 284 Energy 323
9.5 How Does Transport Occur across Biological 10.4 What Are Nucleic Acids? 324
Membranes? 293 The Base Sequence of a Nucleic Acid Is Its Defining
9.6 What Is Passive Diffusion? 294 Characteristic 325
9.7 How Does Facilitated Diffusion Occur? 294 10.5 What Are the Different Classes of Nucleic
Membrane Channel Proteins Facilitate Diffusion 295 Acids? 326
The Bacillus cereus NaK Channel Uses a Variation The Fundamental Structure of DNA Is a Double
on the K1 Selectivity Filter 297 Helix 326
CorA Is a Pentameric Mg21 Channel 298 Various Forms of RNA Serve Different Roles in
Cells 330
Chloride, Water, Glycerol, and Ammonia
Flow through Single-Subunit Pores 299 A Deeper Look: The RNA World and Early
Evolution 334
9.8 How Does Energy Input Drive Active Transport
The Chemical Differences between DNA and RNA Have
Processes? 300 Biological Significance 334
ll Active Transport Systems Are Energy-Coupling
A
Devices 300
10.6 Are Nucleic Acids Susceptible to Hydrolysis? 335
RNA Is Susceptible to Hydrolysis by Base, but DNA
Many Active Transport Processes Are Driven by
Is Not 335
ATP 301
The Enzymes That Hydrolyze Nucleic Acids Are
A Deeper Look: Cardiac Glycosides: Potent Drugs from
Phosphodiesterases 335
Ancient Times 305
Nucleases Differ in Their Specificity for Different Forms
ABC Transporters Use ATP to Drive Import and Export
of Nucleic Acid 335
Functions and Provide Multidrug Resistance 306
Restriction Enzymes Are Nucleases That Cleave
9.9 How Are Certain Transport Processes Driven by Light Double-Stranded DNA Molecules 337
Energy? 308
Type II Restriction Endonucleases Are Useful
9.10 How Is Secondary Active Transport Driven by Ion for Manipulating DNA in the Lab 337
Gradients? 310 Restriction Endonucleases Can Be Used to Map
Na1 and H1 Drive Secondary Active Transport 310 the Structure of a DNA Fragment 339
AcrB Is a Secondary Active Transport System 310 Foundational Biochemistry 341
Foundational Biochemistry 311 Problems 341
Problems 312 Further Reading 343
Further Reading 314
10 11
Structure of Nucleic Acids 345
Nucleotides and Nucleic Acids 317
11.1 How Do Scientists Determine the Primary Structure
10.1 What Are the Structure and Chemistry of Nucleic Acids? 345
of Nitrogenous Bases? 318 he Nucleotide Sequence of DNA Can Be Determined
T
Three Pyrimidines and Two Purines Are Commonly from the Electrophoretic Migration of a Defined Set of
Found in Cells 318 Polynucleotide Fragments 346
The Properties of Pyrimidines and Purines Can Be Traced Sanger’s Chain Termination or Dideoxy Method Uses
to Their Electron-Rich Nature 319 DNA Replication to Generate a Defined Set of
Polynucleotide Fragments 346
xii Detailed Contents
ext-Generation Sequencing by Synthesis 348

N MC Proteins Establish Chromosome Organization and
S
High-Throughput DNA Sequencing Based on Proton Mediate Chromosome Dynamics 375
Detection 349 11.6 How Can Nucleic Acids Be Synthesized
Single-Molecule Real-Time Sequencing 351 Chemically? 375
Human Biochemistry: The Human Genome hosphoramidite Chemistry Is Used to Form
P
Project 352 Oligonucleotides from Nucleotides 376
Oxford Nanopore Technologies (ONT) Real-Time Genes and Even Chromosomes Can Be Synthesized
Sequencing 352 Chemically 376
Bioinformatics—Functional Genomics, Proteomics, and 11.7 What Are the Secondary and Tertiary
More 353 Structures of RNA? 378
11.2 What Sorts of Secondary Structures Can ransfer RNA Adopts Higher-Order Structure Through
T
Double-Stranded DNA Molecules Adopt? 354 Intrastrand Base Pairing 380
Conformational Variation in Polynucleotide Messenger RNA Adopts Higher-Order Structure Through
Strands 354 Intrastrand Base Pairing 381
DNA Usually Occurs in the Form of Double-Stranded Ribosomal RNA Also Adopts Higher-Order Structure
Helices 355 Through Intrastrand Base Pairing 382
Watson–Crick Base Pairs Have Virtually Identical Aptamers Are Oligonucleotides Specifically Selected for
Dimensions 355 Their Ligand-Binding Ability 384
The DNA Double Helix Is a Stable Structure 355 Foundational Biochemistry 386
Double Helical Structures Can Adopt a Number of Stable Problems 387
Conformations 357
Further Reading 389
A-Form DNA Is an Alternative Form of Right-Handed
12
DNA 357
Z-DNA Is a Conformational Variation in the Form of a
Left-Handed Double Helix 358
The Double Helix Is Flexible 361
Human Biochemistry: DNA Methylation, CpG Islands, Recombinant DNA, Cloning, Gene Editing, and
and Epigenetics 362 Synthetic Biology—An Introduction 393
Alternative Hydrogen-Bonding Interactions Give Rise to 12.1 What Is DNA Cloning? 394
Novel DNA Structures: Cruciforms, Triplexes, and
Plasmids Are Very Useful in Cloning Genes 394
Quadruplexes 362
Shuttle Vectors Are Plasmids That Can Propagate in Two
11.3 Can the Secondary Structure of DNA Different Organisms 399
Be Denatured and Renatured? 366 Artificial Chromosomes Can Be Created from
hermal Denaturation of DNA Can Be Observed by
T Recombinant DNA 399
Changes in UV Absorbance 367
12.2 What Is a DNA Library? 400
pH Extremes or Strong H-Bonding Solutes also Denature
Genomic Libraries Are Prepared from the Total DNA in an
DNA Duplexes 367
Organism 400
Single-Stranded DNA Can Renature to Form DNA
Critical Developments in Biochemistry: Combinatorial
Duplexes 367
Libraries 400
A Deeper Look: The Buoyant Density of DNA 368
Libraries Can Be Screened for the Presence of Specific
The Rate of DNA Renaturation Is an Index of DNA Genes 401
Sequence Complexity 368
Probes for Screening Libraries Can Be Prepared
Nucleic Acid Hybridization: Different DNA Strands of in a Variety of Ways 402
Similar Sequence Can Form Hybrid Duplexes 369
PCR Is Used to Clone and Amplify Specific
11.4 How Does DNA Adopt Structures of Genes 402
Higher Complexity? 370 Critical Developments in Biochemistry: Identifying
Supercoils Are One Kind of Structural Complexity in Specific DNA Sequences by Southern Blotting
DNA 370 (Southern Hybridization) 404
Supercoiled DNA Is Defined by Its Linking Number 370 cDNA Libraries Are DNA Libraries Prepared from
Enzymes Can Add or Remove Supercoils 371 mRNA 405
11.5 What Is the Structure of Eukaryotic DNA Microarrays (Gene Chips) Are Arrays of Different
Chromosomes? 372 Oligonucleotides Immobilized on a Chip 407
Nucleosomes Are the Fundamental Structural Unit in 12.3 Can the Genes in Libraries Be Transcribed
Chromatin 373 and Translated? 408
Higher-Order Structural Organization of Chromatin Gives Expression Vectors Are Engineered So That the RNA or
Rise to Chromosomes 374 Protein Products of Cloned Genes Can Be Synthesized 408
Detailed Contents xiii
Reporter Gene Constructs Are Chimeric DNA Molecules Coenzymes and Cofactors Are Nonprotein Components
Composed of Gene Regulatory Sequences Positioned Essential to Enzyme Activity 437
Next to an Easily Expressible Gene Product 411 13.2 How Can the Rate of an Enzyme-Catalyzed Reaction
Specific Protein–Protein Interactions Can Be Identified Be Defined in a Mathematical Way? 438
Using the Yeast Two-Hybrid System 412
Chemical Kinetics Provides a Foundation for Exploring
In Vitro Mutagenesis—Introducing Changes into Enzyme Kinetics 438
Expressed Proteins 413
Bimolecular Reactions Are Reactions Involving Two
12.4 How Is RNA Interference Used to Reveal the Function Reactant Molecules 439
of Genes? 413 Catalysts Lower the Free Energy of Activation for a
12.5 Gene Therapy: Is It Possible for Scientists to Alter or Reaction 439
Rewrite the Genome of an Organism? 414 Decreasing DG‡ Increases Reaction Rate 440
Human Gene Therapy Can Repair Genetic 13.3 What Equations Define the Kinetics of Enzyme‑
Deficiencies 415 Catalyzed Reactions? 441
Viruses as Vectors in Human Gene Therapy 416 The Substrate Binds at the Active Site of an Enzyme 441
Genome Engineering 416 The Michaelis–Menten Equation Is the Fundamental
Genome Editing with CRISPR-Cas9 417 Equation of Enzyme Kinetics 442
A Deeper Look: The Biological Role of CRISPR-Cas Rate Calculations Assume That [ES] Remains Constant
Systems: Adaptive immunity in Bacteria 418 During an Enzymatic Reaction 442
Base Editing with CRISPR-Cas9 420 A Calculations Are Simplified If Velocity Measurements
Prime Editing with CRISPR-Cas9 421 Are Made Immediately after Adding S 442
Gene Silencing with CRISPR-Cas9 421 The Michaelis Constant, Km, Is Defined as
(k21 1 k2)/k1 443
12.6 How Does High-Throughput Technology Allow Global
When [S] 5 Km, v 5 Vmax/2 444
Study of Millions of Genes or Molecules at Once? 421
Plots of v versus [S] Illustrate the Relationships between
High-Throughput Screening 422
Vmax, Km, and Reaction Order 444
High-Throughput RNAi Screening of Mammalian
Turnover Number Defines the Activity of One Enzyme
Genomes 422
Molecule 445
High-Throughput Protein Screening 422
The Ratio, kcat/Km, Defines the Catalytic Efficiency of an
12.7 What Is the Field of Synthetic Biology? 423 Enzyme 445
iGEM and BioBricks (Registry of Standard Biological Linear Plots Can Be Derived from the Michaelis–Menten
Parts) 423 Equation 446
Metabolic Engineering 424 A Deeper Look: An Example of the Effect of Amino Acid
Synthetic Genomes 425 Substitutions on Km and kcat: Wild-Type and Mutant
Foundational Biochemistry 427 Forms of Human Sulfite Oxidase 448
Problems 428 Nonlinear Lineweaver–Burk or Hanes–Woolf Plots Are a
Property of Regulatory Enzymes 448
Further Reading 429
Enzymatic Activity Is Strongly Influenced by pH 448
The Response of Enzymatic Activity to Temperature Is
Complex 448
Part II Protein Dynamics 433
13.4 What Can Be Learned from the Inhibition of Enzyme
13
Activity? 449
Enzymes May Be Inhibited Reversibly or Irreversibly 449
Reversible Inhibitors May Bind at the Active Site or at
Some Other Site 450
Enzymes—Kinetics and Specificity 433
A Deeper Look: The Equations of Competitive
Enzymes Are the Agents of Metabolic Function 434 Inhibition 451
13.1 What Characteristic Features Define Enzymes? 434 Enzymes Also Can Be Inhibited in an Irreversible
Catalytic Power Is Defined as the Ratio of the Enzyme- Manner 453
Catalyzed Rate of a Reaction to the Uncatalyzed Rate 435 13.5 What Is the Kinetic Behavior of Enzymes Catalyzing
Specificity Is the Term Used to Define the Selectivity of Bimolecular Reactions? 455
Enzymes for Their Substrates 435
Human Biochemistry: Viagra—An Unexpected Outcome
Regulation of Enzyme Activity Ensures That the Rate of in a Program of Drug Design 456
Metabolic Reactions Is Appropriate to Cellular
The Conversion of AEB to PEQ Is the Rate-Limiting Step
Requirements 435
in Random, Single-Displacement Reactions 457
Enzyme Nomenclature Provides a Systematic Way of
In an Ordered, Single-Displacement Reaction, the
Naming Metabolic Reactions 435
Leading Substrate Must Bind First 458
xiv Detailed Contents
Double-Displacement (Ping-Pong) Reactions Proceed Via Noncatalytic Residues May Still Play a Role in Catalysis in
Formation of a Covalently Modified Enzyme Enzyme Active Sites 490
Intermediate 459 14.6 What Can Be Learned from the Mechanisms of Some
Exchange Reactions Are One Way to Diagnose Typical Enzymes? 491
Bisubstrate Mechanisms 461
Serine Proteases 491
Multisubstrate Reactions Can Also Occur in Cells 461
The Digestive Serine Proteases 491
13.6 How Can Enzymes Be So Specific? 461 The Chymotrypsin Mechanism in Detail: Kinetics 493
The Lock-and-Key Hypothesis Was the First Explanation The Serine Protease Mechanism in Detail: Events at the
for Specificity 462 Active Site 493
The Induced-Fit Hypothesis Provides a More Accurate The Aspartic Proteases 496
Description of Specificity 462
The Mechanism of Action of Aspartic Proteases 497
Induced Fit Favors Formation of the Transition State 462
The HIV-1 Protease Is an Aspartic Protease 497
Specificity and Reactivity 462
Critical Developments in Biochemistry: Frances Arnold
13.7 Are All Enzymes Proteins? 463 and Directed Evolution of Enzymes 499
RNA Molecules That Are Catalytic Have Been Termed Chorismate Mutase: A Model for Understanding Catalytic
Ribozymes 463 Power and Efficiency 499
Antibody Molecules Can Have Catalytic Activity 464 Human Biochemistry: Protease Inhibitors-Game
13.8 Is It Possible to Design an Enzyme to Catalyze Any Changers for AIDS Patients 502
Desired Reaction? 466 Foundational Biochemistry 504
A Designer Enzyme for Bioremediation 467 Problems 505
A Case Study for Designer Enzyme Development — Kemp Further Reading 508
Eliminases 467
15
Problems 469
Further Reading 471
Enzyme Regulation 511
14 15.1 What Factors Influence Enzymatic Activity? 511

he Availability of Substrates and Cofactors Usually
T
Determines How Fast the Reaction Goes 512
Mechanisms of Enzyme Action 475 As Product Accumulates, the Apparent Rate
14.1 What Are the Magnitudes of Enzyme-Induced Rate of the Enzymatic Reaction Will Decrease 512
Accelerations? 475 Genetic Regulation of Enzyme Synthesis Determines
the Amount of Enzyme Present at Any Moment 512
14.2 What Role Does Transition-State Stabilization Play in
Enzyme Activity Can Be Regulated Allosterically 512
Enzyme Catalysis? 477
Enzyme Activity Can Be Regulated through Covalent
14.3 How Does Destabilization of the Enzyme-Substrate Modification 513
Complex Affect Enzyme Catalysis? 478 Zymogens Are Inactive Precursors of Enzymes 513
14.4 What Are Transition State Analogs and How Tightly Isozymes Are Enzymes with Slightly Different Subunits
Do They Bind to the Active Sites of Enzymes? 479 and Kinetic Properties 514
A Deeper Look: Transition-State Analogs Make Our 15.2 What Are the General Features of Allosteric
World Better 480 Regulation? 516
14.5 What Are the Mechanisms of Enzyme Catalysis? 483 egulatory Enzymes Have Certain Exceptional
R
Enzymes Facilitate Formation of Near-Attack Properties 516
Conformations 483 15.3 Can Allosteric Regulation Be Explained by Conforma-
A Deeper Look: How to Read and Write Mechanisms 484 tional Changes in Proteins? 517
Protein Motions Are Essential to Enzyme Catalysis 484 he Symmetry Model for Allosteric Regulation Is Based
T
Covalent Catalysis 486 on Two Conformational States for a Protein 517
General Acid-Base Catalysis 487 The Sequential Model for Allosteric Regulation Is Based
Low-Barrier Hydrogen Bonds 488 on Ligand-Induced Conformational Changes 517
Quantum Mechanical Tunneling in Electron and Proton The Notable Difference between the MWC and KNF
Transfers 489 Models 519
Human Biochemistry: Antibiotic Resistance by Changes in the Oligomeric State of a Protein
Superbugs 489 Can Also Give Allosteric Behavior 519
Metal Ion Catalysis 490
Detailed Contents xv
15.4 What Kinds of Covalent Modification Regulate Human Biochemistry: Hemoglobin and Nitric Oxide 536
the Activity of Enzymes? 519 Sickle-Cell Disease Is Characterized by Abnormal Red
ovalent Modification through Reversible
C Blood Cells 537
Phosphorylation 519 Sickle-Cell Disease Has Been Characterized as a
Protein Kinases: Target Recognition and Intrasteric Molecular Disease 537
Control 519 Foundational Biochemistry 538
Phosphorylation Is Not the Only Form of Covalent Problems 539
Modification That Regulates Enzyme Function 522
Further Reading 541
Acetylation Is a Prominent Modification
16
for the Regulation of Metabolic Enzymes 522
15.5 Is the Activity of Some Enzymes Controlled by Both
Allosteric Regulation and Covalent Modification? 523
he Glycogen Phosphorylase Reaction Converts
T
Glycogen into Readily Usable Fuel in the Form of
Molecular Motors 543
Glucose-1-Phosphate 523 16.1 What Are the General Features of Molecular
Glycogen Phosphorylase Is a Homodimer 523 Motors? 543
Glycogen Phosphorylase Activity Is Regulated 16.2 What Is the Molecular Mechanism
Allosterically 524 of Muscle Contraction? 544
Covalent Modification of Glycogen Phosphorylase uscle Contraction Is Triggered by Ca 21 Release
M
Overrides Allosteric Regulation 526 from Intracellular Stores 544
Enzyme Cascades Regulate Glycogen Phosphorylase Human Biochemistry: Medical Applications of Smooth
Covalent Modification 526 Muscle Effectors 545
15.6 What Is the Relationship between Quaternary Structure The Molecular Structure of Skeletal Muscle
and Allosteric Regulation? 528 Is Based on Actin and Myosin 545
he Comparative Biochemistry of Myoglobin and
T The Mechanism of Muscle Contraction Is Based on
Hemoglobin Reveals Insights into Allostery 528 Sliding Filaments 548
Myoglobin Is an Oxygen-Storage Protein 529 A Deeper Look: The P-Loop NTPases—Energy to Run
O2 Binds to the Mb Heme Group 529 the Motors 549
O2 Binding Alters Mb Conformation 529 16.3 What Are the Molecular Motors That Orchestrate the
A Deeper Look: The Oxygen-Binding Curves of Mechanochemistry of Microtubules? 551
Myoglobin and Hemoglobin 530 ilaments of the Cytoskeleton Are Highways
F
Cooperative Binding of Oxygen by Hemoglobin That Move Cellular Cargo 552
Has Important Physiological Significance 531 Three Classes of Motor Proteins Move Intracellular
Hemoglobin Has an a2b2 Tetrameric Structure 531 Cargo 553
Oxygenation Markedly Alters the Quaternary Dyneins Move Organelles in a Plus-to-Minus Direction;
Structure of Hb 532 Kinesins, in a Minus-to-Plus Direction 554
Movement of the Heme Iron by Less Than 0.04 nm Human Biochemistry: Effectors of Microtubule
Induces the Conformational Change in Hemoglobin 532 Polymerization as Therapeutic Agents 555
The Physiological Significance of the Hb:O2 Cytoskeletal Motors Are Highly Processive 555
Interaction 532 ATP Binding and Hydrolysis Drive Hand-over-Hand
The Oxy and Deoxy Forms of Hemoglobin Represent Movement of Kinesin 557
Two Different Conformational States 533 Conformation Changes in a Hexameric Ring
The Allosteric Behavior of Hemoglobin Has Both Drive the Dynein Motor 558
Symmetry (MWC) Model and Sequential (KNF) 16.4 How Do Molecular Motors Unwind DNA? 558
Model Components 533 egative Cooperativity Facilitates Hand-over-Hand
N
H1 Promotes the Dissociation of Oxygen from Movement 561
Hemoglobin 533 Papillomavirus E1 Helicase Moves along DNA as on a
CO2 Also Promotes the Dissociation of O2 from Spiral Staircase 562
Hemoglobin 534
16.5 How Do Bacterial Flagella Use a Proton Gradient
2,3-Bisphosphoglycerate Is an Important Allosteric
to Drive Rotation? 564
Effector for Hemoglobin 535
The Flagellar Rotor Is a Complex Structure 565
BPG Binding to Hb Has Important Physiological
Significance 535 Gradients of H1 and Na1 Drive Flagellar Rotors 565
Fetal Hemoglobin Has a Higher Affinity for O2 The Flagellar Rotor Self-Assembles in a
Because It Has a Lower Affinity for BPG 535 Spontaneous Process 565
xvi Detailed Contents
lagellar Filaments Are Composed of Protofilaments of

F Mutations Create Specific Metabolic Blocks 588
Flagellin 566 Isotopic Tracers Can Be Used as Metabolic Probes 588
Motor Reversal Involves Conformation Switching NMR Spectroscopy Is a Noninvasive Metabolic Probe 589
of Motor and Filament Proteins 566 Cell Fractionation Reveals Which Compartment Contains
Foundational Biochemistry 568 a Metabolic Pathway 589
Problems 568 Metabolic Pathways Are Also Time-Dependent 591
Further Reading 570 17.5 What Can the Metabolome Tell Us about a Biological
System? 592
Part III Metabolism and Its Regulation 573 17.6 What Food Substances Form the Basis
of Human Nutrition? 596
17
Humans Require Protein 596
Carbohydrates Provide Metabolic Energy 597
Lipids Are Essential, but in Moderation 597
Metabolism: An Overview 573 Foundational Biochemistry 597

Problems 598
17.1 Is Metabolism Similar in Different Organisms? 573
Further Reading 600
Living Things Vary in Their Carbon and Energy
Requirements 574
Oxygen Is Essential to Life for Aerobes 574
The Flow of Energy in the Biosphere and the Carbon and
Oxygen Cycles Are Intimately Related 574
18
A Deeper Look: Calcium Carbonate—A Biological Sink Glycolysis 603
for CO2 575 18.1 What Are the Essential Features of Glycolysis? 603
17.2 What Can Be Learned from Metabolic Maps? 575 18.2 Why Are Coupled Reactions Important in
The Metabolic Map Can Be Viewed as a Set of Dots and Glycolysis? 605
Lines 575
18.3 What Are the Chemical Principles and Features of the
Alternative Metabolic Pathway Models Can Provide New
First Phase of Glycolysis? 606
Insights into Pathways 577
eaction 1: Glucose Is Phosphorylated by Hexokinase
R
Metabolism Is a Network 578
or Glucokinase—The First Priming Reaction 606
Metabolic Pathways with Multiple Enzymes May Take
A Deeper Look: Glucokinase—An Enzyme with Different
Different Forms 579
Roles in Different Cells 609
17.3 How Do Anabolic and Catabolic Processes Form the Reaction 2: Phosphoglucoisomerase Catalyzes
Core of Metabolic Pathways? 580 the Isomerization of Glucose-6-Phosphate 609
Anabolism Is Biosynthesis 580 Reaction 3: ATP Drives a Second Phosphorylation
Anabolism and Catabolism Are Not Mutually Exclusive 580 by Phosphofructokinase—The Second Priming
The Pathways of Catabolism Converge to a Few End Reaction 610
Products 581 Reaction 4: Cleavage by Fructose Bisphosphate
Anabolic Pathways Diverge, Synthesizing an Astounding Aldolase Creates Two 3-Carbon Intermediates 612
Variety of Biomolecules from a Limited Set of Building Reaction 5: Triose Phosphate Isomerase
Blocks 581 Completes the First Phase of Glycolysis 613
Amphibolic Intermediates Play Dual Roles 583 Human Biochemistry: Methylglyoxal and Advanced
Corresponding Pathways of Catabolism and Anabolism Glycation End-Products—The Dark Side of
Differ in Important Ways 583 Glycolysis 614
Metabolic Regulation Requires Different Pathways for 18.4 What Are the Chemical Principles and Features of the
Oppositely Directed Metabolic Sequences 583 Second Phase of Glycolysis? 615
ATP Is Produced and Consumed in a Cellular Energy eaction 6: Glyceraldehyde-3-Phosphate Dehydrogenase
R
Cycle 583 Creates a High-Energy Intermediate 615
NAD1 Collects Electrons Released in Catabolism 584 Reaction 7: Phosphoglycerate Kinase Is the Break-Even
NADPH Provides the Reducing Power for Anabolic Reaction 615
Processes 585 Reaction 8: Phosphoglycerate Mutase Catalyzes a
Coenzymes and Vitamins Provide Unique Chemistry and Phosphoryl Transfer 617
Essential Nutrients to Pathways 586 Reaction 9: Dehydration by Enolase Creates PEP 618
17.4 What Experiments Can Be Used to Elucidate Reaction 10: Pyruvate Kinase Yields More ATP 618
Metabolic Pathways? 587 Human Biochemistry: Pyruvate Kinase M2 Moonlights
nzyme Inhibitors Can Be Used to Reveal Individual
E as a Protein Kinase in Cancer 620
Metabolic Reactions 587
Detailed Contents xvii
18.5 What Are the Metabolic Fates of NADH and Pyruvate 19.5 What Are the Energetic Consequences
Produced in Glycolysis? 621 of the TCA Cycle? 651
Anaerobic Metabolism of Pyruvate Leads to Lactate or he Carbon Atoms of Acetyl-CoA Have Different Fates in
T
Ethanol 621 the TCA Cycle 652
Lactate Accumulates Under Anaerobic Conditions in A Deeper Look: Steric Preferences in NAD1-Dependent
Animal Tissues 622 Dehydrogenases 654
Critical Developments in Biochemistry: The Warburg 19.6 Can the TCA Cycle Provide Intermediates
Effect and Cancer 623 for Biosynthesis? 654
18.6 How Do Cells Regulate Glycolysis? 624 Human Biochemistry: Leber’s Hereditary Optic
18.7 Are Substrates Other Than Glucose Neuropathy Arises from Mitochondrial DNA
Used in Glycolysis? 624 Mutations 655
ructose Catabolism in Liver Is Unregulated—
F 19.7 What Are the Anaplerotic, or Filling Up,
and Potentially Harmful 624 Reactions? 656
Mannose Enters Glycolysis in Two Steps 626 A Deeper Look: Anaplerosis Plays a Critical Role in
Galactose Enters Glycolysis via the Leloir Pathway 626 Insulin Secretion 657
Human Biochemistry: Tumor Diagnosis Using Positron A Deeper Look: Fool’s Gold and the Reductive Citric
Emission Tomography (PET) 626 Acid Cycle—The First Metabolic Pathway? 658
Glycerol Can Also Enter Glycolysis 628 19.8 How Is the TCA Cycle Regulated? 658
18.8 How Do Cells Respond to Hypoxic Stress? 628 yruvate Dehydrogenase Is Regulated
P
by Phosphorylation/Dephosphorylation 659
Human Biochemistry: Lactose and Lactose Intolerance:
From Mother’s Milk to Yogurt 629 Isocitrate Dehydrogenase Is Strongly Regulated 660
Foundational Biochemistry 631 Regulation of TCA Cycle Enzymes by Acetylation 660
Human Biochemistry: TCA Metabolites Play Roles in
Problems 631
Many Pathways via Post-Translational Modifications 661
Further Reading 633
Two Covalent Modifications Regulate E. coli Isocitrate
Dehydrogenase 661
19
TCA Metabolites Can Act as Cellular Signals 662
The TCA Cycle Operates as a Metabolon 662
19.9 Can Any Organisms Use Acetate as Their Sole Carbon
The Tricarboxylic Acid Cycle 635 Source? 662
he Glyoxylate Cycle Operates in Specialized
T
19.1 What Is the Chemical Logic of the TCA Cycle? 636
Organelles 663
19.2 How Is Pyruvate Oxidatively Decarboxylated Isocitrate Lyase Short-Circuits the TCA Cycle
to Acetyl-CoA? 639 by Producing Glyoxylate and Succinate 664
A Deeper Look: The Coenzymes of the Pyruvate The Glyoxylate Cycle Helps Plants Grow in the Dark 665
Dehydrogenase Complex 642
Glyoxysomes Must Borrow Three Reactions from
19.3 How Are Two CO2 Molecules Produced Mitochondria 665
from Acetyl-CoA? 644 Foundational Biochemistry 666
he Citrate Synthase Reaction Initiates the
T Problems 666
TCA Cycle 644
Further Reading 668
Citrate Is Isomerized by Aconitase to Form
Isocitrate 645
Isocitrate Dehydrogenase Catalyzes the First
Oxidative Decarboxylation in the Cycle 647
α-Ketoglutarate Dehydrogenase Catalyzes the Second
20
Oxidative Decarboxylation of the TCA Cycle 648 Electron Transport and Oxidative
19.4 How Is Oxaloacetate Regenerated to Complete Phosphorylation 671
the TCA Cycle? 648 20.1 Where in the Cell Do Electron Transport and Oxidative
uccinyl-CoA Synthetase Catalyzes Substrate-Level
S Phosphorylation Occur? 671
Phosphorylation 649 itochondrial Functions Are Localized in Specific
M
Succinate Dehydrogenase Is FAD-Dependent 650 Compartments 672
Fumarase Catalyzes the Trans-Hydration Human Biochemistry: Mitochondrial Dynamics in
of Fumarate to Form l-Malate 650 Human Diseases 673
Malate Dehydrogenase Completes the Cycle The Mitochondrial Matrix Contains the Enzymes of the
by Oxidizing Malate to Oxaloacetate 651 TCA Cycle 674
xviii Detailed Contents
20.2 How Is the Electron-Transport Chain Organized? 674 20.7 How Do Mitochondria Mediate Apoptosis? 704
The Electron-Transport Chain Can Be Isolated in Four Cytochrome c Triggers Apoptosome Assembly 706
Complexes 675 Foundational Biochemistry 707
Complex I Oxidizes NADH and Reduces Coenzyme Q 676 Problems 707
Human Biochemistry: Solving a Medical Mystery
Further Reading 710
Revolutionized Our Treatment of Parkinson’s Disease 679
21
Complex II Oxidizes Succinate and Reduces Coenzyme
Q 680
Complex III Mediates Electron Transport from Coenzyme
Q to Cytochrome c 681
Complex IV Transfers Electrons from Cytochrome c Photosynthesis 713
to Reduce Oxygen on the Matrix Side 684 21.1 What Are the General Properties of
Proton Transport Across Cytochrome c Oxidase Photosynthesis? 714
Is Coupled to Oxygen Reduction 686 Photosynthesis Occurs in Membranes 714
Reversal of Complex II May Short-Circuit Photosynthesis Consists of Both Light Reactions
the Electron Transfer Pathway 687 and Dark Reactions 715
The Complexes of Electron Transport Water Is the Ultimate Electron Donor
May Function as Supercomplexes 687 for Photosynthetic NADP1 Reduction 716
Electron Transfer Energy Stored in a Proton
21.2 How Is Solar Energy Captured by Chlorophyll? 717
Gradient: The Mitchell Hypothesis 689
hlorophylls and Accessory Light-Harvesting Pigments
C
20.3 What Are the Thermodynamic Implications of Absorb Light of Different Wavelengths 717
Chemiosmotic Coupling? 690 The Light Energy Absorbed by Photosynthetic
20.4 How Does a Proton Gradient Drive Pigments Has Several Possible Fates 718
the Synthesis of ATP? 690 The Transduction of Light Energy into Chemical
ATP Synthase Is Composed of F1 and F0 Complexes 691 Energy Involves Oxidation–Reduction 719
he Catalytic Sites of ATP Synthase Adopt
T Photosynthetic Units Consist of Many Chlorophyll
Three Different Conformations 693 Molecules but Only a Single Reaction Center 720
Boyer’s 18O Exchange Experiment Identified the 21.3 What Kinds of Photosystems Are Used to Capture
Energy-Requiring Step 693 Light Energy? 721
The Binding Change Mechanism Describes hlorophyll Exists in Plant Membranes in Association
C
the Events of Rotational Catalysis 694 with Proteins 721
Proton Flow Through F0 Drives Rotation PSI and PSII Participate in the Overall Process of
of the Motor and Synthesis of ATP 694 Photosynthesis 721
How Many Protons Are Required to Make an ATP? The Pathway of Photosynthetic Electron Transfer Is Called
It Depends on the Organism 696 the Z Scheme 722
The Mitchell Model Has Been Confirmed Oxygen Evolution Requires the Accumulation of Four
in a Reconstitution Experiment 696 Oxidizing Equivalents in PSII 722
Inhibitors of Oxidative Phosphorylation Electrons Are Taken from H2O to Replace Electrons Lost
Reveal Insights About the Mechanism 697 from P680 724
Uncouplers Disrupt the Coupling of Electron Electrons from PSII Are Transferred to PSI via the
Transport and ATP Synthase 698 Cytochrome b6 f Complex 724
ATP–ADP Translocase Mediates the Movement of ATP Plastocyanin Transfers Electrons
and ADP Across the Mitochondrial Membrane 698 from the Cytochrome b6 f Complex to PSI 724
Human Biochemistry: Endogenous Uncouplers—Novel 21.4 What Is the Molecular Architecture of Photosynthetic
Proteins with Many Beneficial Effects 699
Reaction Centers? 725
20.5 What Is the P/O Ratio for Mitochondrial The R. viridis Photosynthetic Reaction Center Is an
Oxidative Phosphorylation? 700 Integral Membrane Protein 725
20.6 How Are the Electrons of Cytosolic NADH Photosynthetic Electron Transfer by the R. viridis
Fed into Electron Transport? 701 Reaction Center Leads to ATP Synthesis 726
Glycerophosphate Shuttle Ensures Efficient Use of
The The Molecular Architecture of PSII Resembles
Cytosolic NADH 701 the R. viridis Reaction Center Architecture 727
The Malate–Aspartate Shuttle Is Reversible 702 How Does PSII Generate O2 from H2O? 729
The Net Yield of ATP from Glucose Oxidation The Molecular Architecture of PSI Resembles the
Depends on the Shuttle Used 703 R. viridis Reaction Center and PSII Architecture 730
3.5 Billion Years of Evolution Have Resulted How Do Green Plants Carry Out Photosynthesis? 731
in a Very Efficient System 704
Detailed Contents xix
21.5 What Is the Quantum Yield of Photosynthesis? 731 Human Biochemistry: The Chemistry of Glucose
The H1/ATP Ratio Determines ATP Yield per Monitoring Devices 752
Quantum 732 Gluconeogenesis Is Not Merely the Reverse of
Calculation of the Photosynthetic Energy Requirements Glycolysis 753
for Hexose Synthesis Depends on H1/hy and ATP/H1 Gluconeogenesis—Something Borrowed, Something
Ratios 732 New 753
21.6 How Does Light Drive the Synthesis of ATP? 732 Four Enzyme Reactions Are Unique to
The Mechanism of Photophosphorylation Is Gluconeogenesis 755
Chemiosmotic 733 Human Biochemistry: Metformin—a Diabetes Drug
CF1CF0 –ATP Synthase Is the Chloroplast Equivalent with Multiple Actions 758
of the Mitochondrial F1F0 –ATP Synthase 733 22.2 How Is Gluconeogenesis Regulated? 759
Photophosphorylation Can Occur in Either Critical Developments in Biochemistry: The Pioneering
a Noncyclic or a Cyclic Mode 733 Studies of Carl and Gerty Cori 760
Cyclic Photophosphorylation Generates ATP but Not Gluconeogenesis Is Regulated by Allosteric and
NADPH or O2 734 Substrate-Level Control Mechanisms 760
21.7 How Is Carbon Dioxide Used to Make A Deeper Look: TIGAR—A p53-Induced Enzyme That
Organic Molecules? 735 Mimics Fructose-2,6-Bisphosphatase 762
ibulose-1,5-Bisphosphate Is the CO2 Acceptor in CO2
R Substrate Cycles Provide Metabolic Control
Fixation 736 Mechanisms 763
2-Carboxy-3-Keto-Arabinitol Is an Intermediate 22.3 How Are Glycogen and Starch Catabolized in
in the Ribulose-1,5-Bisphosphate Carboxylase Animals? 764
Reaction 736 Dietary Starch Breakdown Provides Metabolic Energy 764
Ribulose-1,5-Bisphosphate Carboxylase Exists in Metabolism of Tissue Glycogen Is Regulated 765
Inactive and Active Forms 737
22.4 How Is Glycogen Synthesized? 766
CO2 Fixation into Carbohydrate Proceeds
lucose Units Are Activated for Transfer by Formation of
G
via the Calvin–Benson Cycle 737
Sugar Nucleotides 766
Rubisco and the Enzymes of the Calvin Cycle
UDP–Glucose Synthesis Is Driven by Pyrophosphate
Serve Three Metabolic Purposes 738
Hydrolysis 766
The Calvin Cycle Reactions Can Account for Net Hexose
Glycogen Synthase Catalyzes Formation of α(18n4)
Synthesis 740
Glycosidic Bonds in Glycogen 767
The Carbon Dioxide Fixation Pathway Is Indirectly
Glycogen Branching Occurs by Transfer of Terminal
Activated by Light 740
Chain Segments 768
Protein–Protein Interactions Mediated by an Intrinsically
Unstructured Protein Also Regulate Calvin–Benson 22.5 How Is Glycogen Metabolism Controlled? 768
Cycle Activity 741 Glycogen Metabolism Is Highly Regulated 768
21.8 How Does Photorespiration Limit CO2 Fixation? 741 Human Biochemistry: Advanced Glycation End
Products—A Serious Complication of Diabetes 769
ropical Grasses Use the Hatch–Slack Pathway
T
to Capture Carbon Dioxide for CO2 Fixation 742 Glycogen Synthase Is Regulated by Covalent
Modification 770
Cacti and Other Desert Plants Capture CO2 at Night 744
Hormones Regulate Glycogen Synthesis and
Degradation 772
Problems 746 Human Biochemistry: Carbohydrate Utilization in
Further Reading 747 Exercise 772
Critical Developments in Biochemistry: O-GlcNAc
22 22.6
Signaling and the Hexosamine Biosynthetic
Pathway 775
How Does Glucose Provide Electrons for
Gluconeogenesis, Glycogen Metabolism, and the Biosynthesis? 776
Pentose Phosphate Pathway 751 he Pentose Phosphate Pathway Operates Mainly in Liver
T
and Adipose Cells 776
22.1 What Is Gluconeogenesis, and How Does The Pentose Phosphate Pathway Begins with Two
It Operate? 752 Oxidative Steps 778
he Substrates for Gluconeogenesis Include Pyruvate,
T There Are Four Nonoxidative Reactions in the Pentose
Lactate, and Amino Acids 752 Phosphate Pathway 779
Nearly All Gluconeogenesis Occurs in the Liver and Human Biochemistry: Aldose Reductase and Diabetic
Kidneys in Animals 752 Cataract Formation 780
xx Detailed Contents
tilization of Glucose-6-P Depends on the Cell’s Need

U egradation of Polyunsaturated Fatty Acids Requires
D
for ATP, NADPH, and Ribose-5-P 783 2,4-Dienoyl-CoA Reductase 809
Critical Developments in Biochemistry: Integrating the A Deeper Look: Can Natural Antioxidants in Certain
Warburg Effect—ATP Consumption Promotes Cancer Foods Improve Fat Metabolism? 811
Metabolism 785 23.5 Are There Other Ways to Oxidize Fatty Acids? 811
Xylulose-5-Phosphate Is a Metabolic Regulator 786 Peroxisomal b-Oxidation Requires FAD-Dependent
Foundational Biochemistry 787 Acyl-CoA Oxidase 811
Problems 787 Branched-Chain Fatty Acids Are Degraded Via
Further Reading 789 a-Oxidation 812
v -Oxidation of Fatty Acids Yields Small Amounts of
23
Dicarboxylic Acids 813
23.6 What Are Ketone Bodies, and What Role Do They Play
in Metabolism? 813
Fatty Acid Catabolism 791 etone Bodies Are a Significant Source of Fuel and
K
Energy for Certain Tissues 813
23.1 How Are Fats Mobilized from Dietary Intake and
Human Biochemistry: Large Amounts of Ketone Bodies
Adipose Tissue? 791 Are Produced in Diabetes Mellitus 813
Modern Diets Are Often High in Fat 791 b-Hydroxybutyrate Is a Signaling Metabolite 815
Triacylglycerols Are a Major Form of Stored Energy in
Animals 792
Problems 816
Hormones Trigger the Release of Fatty Acids from
Adipose Tissue 792 Further Reading 818
Degradation of Dietary Triacylglycerols Occurs Primarily
in the Duodenum 792
Human Biochemistry: Serum Albumin—Tramp Steamer
of the Bloodstream 795
24
A Deeper Look: The Biochemistry of Obesity 796 Lipid Biosynthesis 821
23.2 How Are Fatty Acids Broken Down? 797 24.1 How Are Fatty Acids Synthesized? 821
Coenzyme A Activates Fatty Acids for Degradation 798 Formation of Malonyl-CoA Activates Acetate Units for
Carnitine Carries Fatty Acyl Groups Across the Inner Fatty Acid Synthesis 822
Mitochondrial Membrane 799 Fatty Acid Biosynthesis Depends on the Reductive Power
b-Oxidation Involves a Repeated Sequence of Four of NADPH 822
Reactions 800 Cells Must Provide Cytosolic Acetyl-CoA and Reducing
Repetition of the b-Oxidation Cycle Yields a Succession Power for Fatty Acid Synthesis 822
of Acetate Units 803 Acetate Units Are Committed to Fatty Acid Synthesis by
Human Biochemistry: Exercise Can Reverse the Formation of Malonyl-CoA 824
Consequences of Metabolic Syndrome 804 Acetyl-CoA Carboxylase Is Biotin Dependent and Displays
Complete b-Oxidation of One Palmitic Acid Yields 113.7 Ping-Pong Kinetics 824
Molecules of ATP 805 Acetyl-CoA Carboxylase in Animals Is a Multifunctional
Migratory Birds Travel Long Distances on Energy from Protein 824
Fatty Acid Oxidation 805 Phosphorylation of ACC Modulates Activation by Citrate
Fatty Acid Oxidation Is an Important Source of Metabolic and Inhibition by Palmitoyl-CoA 826
Water for Some Animals 806 Acyl Carrier Proteins Carry the Intermediates in Fatty Acid
23.3 How Are Odd-Carbon Fatty Acids Oxidized? 807 Synthesis 826
-Oxidation of Odd-Carbon Fatty Acids Yields
b In Some Organisms, Fatty Acid Synthesis Takes Place in
Propionyl-CoA 807 Multienzyme Complexes 827
A B12-Catalyzed Rearrangement Yields Succinyl-CoA from Decarboxylation Drives the Condensation of Acetyl-CoA
l-Methylmalonyl-CoA 808 and Malonyl-CoA 827
Net Oxidation of Succinyl-CoA Requires Conversion to Reduction of the b-Carbonyl Group Follows a
Acetyl-CoA 808 Now-Familiar Route 829
A Deeper Look: The Activation of Vitamin B12 808 Eukaryotes Build Fatty Acids on Megasynthase
Complexes 830
23.4 How Are Unsaturated Fatty Acids Oxidized? 809
C16 Fatty Acids May Undergo Elongation and
n Isomerase and a Reductase Facilitate the b-Oxidation
A
Unsaturation 832
of Unsaturated Fatty Acids 809
Detailed Contents xxi
Unsaturation Reactions Occur in Eukaryotes in the 24.5 How Are Lipids Transported Throughout the Body? 856
Middle of an Aliphatic Chain 833 Lipoprotein Complexes Transport Triacylglycerols and
The Unsaturation Reaction May Be Followed by Chain Cholesterol Esters 856
Elongation 834 Human Biochemistry: APOC3—An Apolipoprotein That
Mammals Cannot Synthesize Most Polyunsaturated Fatty Regulates Plasma Triglyceride Levels 857
Acids 834 Lipoproteins in Circulation Are Progressively Degraded by
Arachidonic Acid Is Synthesized from Linoleic Acid by Lipoprotein Lipase 857
Mammals 834 The Structure of the LDL Receptor Involves Five
Regulatory Control of Fatty Acid Metabolism Is an Domains 859
Interplay of Allosteric Modifiers and Defects in Lipoprotein Metabolism Can Lead to Elevated
Phosphorylation–Dephosphorylation Cycles 835 Serum Cholesterol 860
Hormonal Signals Regulate ACC and Fatty Acid Human Biochemistry: New Cholesterol-Lowering Drugs
Biosynthesis 835 Target PCSK9, an LDL Receptor Chaperone 861
Human Biochemistry: v3 and v6—Essential Fatty Acids 24.6 How Are Bile Acids Biosynthesized? 861
with Many Functions 836
Human Biochemistry: Niemann—Pick Type C
24.2 How Are Complex Lipids Synthesized? 837 Disease—A Hydrophobic Handoff Fumbled 862
Glycerolipids Are Synthesized by Phosphorylation and Human Biochemistry: Steroid 5α-Reductase—A Factor
Acylation of Glycerol 838 in Male Baldness, Prostatic Hyperplasia, and Prostate
Eukaryotes Synthesize Glycerolipids from Cancer 863
CDP-Diacylglycerol or Diacylglycerol 838 24.7 How Are Steroid Hormones Synthesized and
Human Biochemistry: Lipins—Phosphatases Essential Utilized? 864
for Triglyceride Synthesis and Other Functions 838
Pregnenolone and Progesterone Are the Precursors of All
Phosphatidylethanolamine Is Synthesized from Other Steroid Hormones 864
Diacylglycerol and CDP-Ethanolamine 841
Cortisol and Other Corticosteroids Regulate a Variety of
Exchange of Ethanolamine for Serine Converts Body Processes 864
Phosphatidylethanolamine to Phosphatidylserine 841
Eukaryotes Synthesize Other Phospholipids Via
CDP-Diacylglycerol 841 Problems 866
Dihydroxyacetone Phosphate Is a Precursor to the Further Reading 868
Plasmalogens 843
Platelet-Activating Factor Is Formed by Acetylation of
1-Alkyl-2-Lysophosphatidylcholine 844
Sphingolipid Biosynthesis Begins with Condensation
25
of Serine and Palmitoyl-CoA 844 Nitrogen Acquisition and Amino Acid
Ceramide Is the Precursor for Other Sphingolipids and Metabolism 871
Cerebrosides 844
25.1 Which Metabolic Pathways Allow Organisms to Live
24.3 How Are Eicosanoids Synthesized, and What Are
on Inorganic Forms of Nitrogen? 871
Their Functions? 847
itrogen Is Cycled between Organisms and the
N
Eicosanoids Are Local Hormones 847
Inanimate Environment 872
Prostaglandins Are Formed from Arachidonate by
Nitrate Assimilation Is the Principal Pathway for
Oxidation and Cyclization 847
Ammonium Biosynthesis 872
A Variety of Stimuli Trigger Arachidonate Release and
Organisms Gain Access to Atmospheric N2 via the
Eicosanoid Synthesis 847
Pathway of Nitrogen Fixation 874
A Deeper Look: The Molecular Basis for the Action of
Nonsteroidal Anti-inflammatory Drugs 849 25.2 What Is the Metabolic Fate of Ammonium? 877
he Citric Acid Cycle Intermediate α-Ketoglutarate Is
T
24.4 How Is Cholesterol Synthesized? 851
Precursor to Both Glutamate and Glutamine 877
Mevalonate Is Synthesized from Acetyl-CoA Via
The Major Pathways of Ammonium Assimilation Lead to
HMG-CoA Synthase 851
Glutamine Synthesis 879
Why Can’t Thiolase Be Used in Fatty Acid Synthesis? 851
25.3 What Regulatory Mechanisms Act on Escherichia coli
Squalene Is Synthesized from Mevalonate 852
Glutamine Synthetase? 880
Human Biochemistry: Statins Lower Serum Cholesterol
Glutamine Synthetase Is Allosterically Regulated 880
Levels 854
Glutamine Synthetase Is Regulated by Covalent
Conversion of Lanosterol to Cholesterol Requires 20
Modification 882
Additional Steps 856
xxii Detailed Contents
Glutamine Synthetase Is Regulated through Gene Human Biochemistry: Folate Analogs as Antimicrobial
Expression 882 and Anticancer Agents 928
Glutamine in the Human Body 883 AMP and GMP Are Synthesized from IMP 928
25.4 How Do Organisms Synthesize Amino Acids? 884 The Purine Biosynthetic Pathway Is Regulated at Several
Human Biochemistry: Human Dietary Requirements for Steps 929
Amino Acids 885 ATP-Dependent Kinases Form Nucleoside Diphosphates
Amino Acids Are Formed from α-Keto Acids by and Triphosphates from the Nucleoside
Transamination 886 Monophosphates 930
A Deeper Look: The Mechanism of the 26.3 Can Cells Salvage Purines? 931
Aminotransferase (Transamination) Reaction 886 26.4 How Are Purines Degraded? 931
The α-Ketoglutarate Family of Amino Acids Includes Glu, Human Biochemistry: Lesch–Nyhan Syndrome—
Gln, Pro, Arg, and Lys 887 HGPRT Deficiency Leads to a Severe Clinical
The Urea Cycle Acts to Excrete Excess N through Arg Disorder 932
Breakdown 889 The Major Pathways of Purine Catabolism Lead to Uric
A Deeper Look: The Urea Cycle as Both an Ammonium Acid 932
and a Bicarbonate Disposal Mechanism 891 Human Biochemistry: Severe Combined
The Oxaloacetate Family of Amino Acids Includes Asp, Immunodeficiency Syndrome—A Lack of Adenosine
Asn, Lys, Met, Thr, and Ile 893 Deaminase Is One Cause of This Inherited Disease 933
The Pyruvate Family of Amino Acids Includes Ala, Val, The Purine Nucleoside Cycle in Skeletal Muscle Serves as
and Leu 897 an Anaplerotic Pathway 933
The 3-Phosphoglycerate Family of Amino Acids Includes Xanthine Oxidase 933
Ser, Gly, and Cys 897 Gout Is a Disease Caused by an Excess of Uric Acid 934
The Aromatic Amino Acids Are Synthesized from Different Animals Oxidize Uric Acid to Form Various
Chorismate 902 Excretory Products 935
A Deeper Look: Amino Acid Biosynthesis Inhibitors as 26.5 How Do Cells Synthesize Pyrimidines? 935
Herbicides 906
he Pyrimidine Biosynthetic Pathway from Carbamoyl-P
T
Histidine Biosynthesis and Purine Biosynthesis Are and Aspartate to UMP 936
Connected by Common Intermediates 907
UMP Synthesis Leads to Formation of the Two Most
25.5 How Does Amino Acid Catabolism Lead into Prominent Ribonucleotides—UTP and CTP 936
Pathways of Energy Production? 909 P yrimidine Biosynthesis Is Regulated at ATCase in
he 20 Common Amino Acids Are Degraded by 20
T Bacteria and at CPS-II in Animals 938
Different Pathways That Converge to Just 7 Metabolic “Metabolic Channeling” by Multifunctional Enzymes of
Intermediates 909 Mammalian Pyrimidine Biosynthesis 939
Human Biochemistry: Amino Acid Metabolism and
26.6 How Are Pyrimidines Degraded? 939
Cancer 916
Animals Differ in the Form of Nitrogen That They 26.7 How Do Cells Form the Deoxyribonucleotides
Excrete 916 That Are Necessary for DNA Synthesis? 940
Human Biochemistry: Hereditary Defects in . coli Ribonucleotide Reductase Has Three Different
E
Phe Catabolism Underlie Alkaptonuria and Nucleotide-Binding Sites 940
Phenylketonuria 916 Thioredoxin Provides the Reducing Power for
Foundational Biochemistry 917 Ribonucleotide Reductase 941
Both the Specificity and the Catalytic Activity of
Problems 918
Ribonucleotide Reductase Are Regulated by Nucleotide
Further Reading 919 Binding 942
26
26.8 How Are Thymine Nucleotides Synthesized? 943
Human Biochemistry: Fluoro-Substituted Pyrimidines
in Cancer Chemotherapy, Fungal Infections, and
Malaria 944
Synthesis and Degradation of Nucleotides 921 A Deeper Look: Fluoro-Substituted Analogs Are Good
26.1 How Do Cells Synthesize Nucleotides? 921 Trojan Horse Inhibitors 945
26.2 How Do Cells Synthesize Purines? 922 Foundational Biochemistry 945

IMP Is the Immediate Precursor to GMP and AMP 922 Problems 946
A Deeper Look: Tetrahydrofolate and One-Carbon Further Reading 948
Units 924
Human Biochemistry: SAICAR Is a Key Signal for
Metabolic Reprogramming in Cancer Cells 926
Detailed Contents xxiii
27
MPK Mediates Many of the Hypothalamic
A
Responses to These Hormones 971
27.7 Can You Really Live Longer by Eating Less? 971
aloric Restriction Leads to Longevity 971
C
Metabolic Integration and Organ
Mutations in the SIR2 Gene Decrease Life Span 972
Specialization 951 SIRT1 Is a Key Regulator in Caloric Restriction 973
27.1 Can Systems Analysis Simplify the Complexity SIRT1, mTORC1, AMPK, CR, and Metabolic Syndrome 973
of Metabolism? 951 Foundational Biochemistry 974
nly a Few Intermediates Interconnect the Major
O
Problems 975
Metabolic Systems 953
ATP and NADPH Couple Anabolism and Catabolism 953 Further Reading 977
Phototrophs Have an Additional Metabolic Part IV Information Transfer 981
System—The Photochemical Apparatus 953
28
27.2 What Underlying Principle Relates ATP Coupling to the
Thermodynamics of Metabolism? 954
The Three Types of Stoichiometries in Cells 954
ATP Coupling Stoichiometry Determines DNA Metabolism: Replication, Recombination,
the Keq for Metabolic Sequences 955
ATP Has Two Metabolic Roles 956
and Repair 981
DNA Metabolism 981
27.3 Is There a Good Index of Cellular Energy Status? 956
denylate Kinase Interconverts ATP, ADP, and AMP 956
A 28.1 How Is DNA Replicated? 982
Energy Charge Relates the ATP Levels to the Total NA Replication Is Bidirectional 982
D
Adenine Nucleotide Pool 956 Replication Requires Unwinding of the DNA Helix 982
Key Enzymes Are Regulated by Energy Charge 957 DNA Replication Is Semidiscontinuous 983
Phosphorylation Potential Is a Measure of Relative ATP The Biochemical Evidence for Semidiscontinuous DNA
Levels 957 Replication 984
27.4 How Is Overall Energy Balance Regulated in Cells? 957 Initiation of DNA Replication 985
The Structure and Regulation of AMPK 958 28.2 What Are the Functions of DNA Polymerases? 985
AMPK Targets Key Enzymes in Energy Production and iochemical Characterization of DNA Polymerases 985
B
Consumption 959 E. coli Cells Have Several Different DNA Polymerases 986
AMPK Controls Whole-Body Energy Homeostasis 959 E. coli DNA Polymerase III Holoenzyme Replicates the E. coli
AMPK Inhibits mTORC1, the Master Growth Regulator Chromosome 986
of Eukaryotic Cells 959 A DNA Polymerase III Holoenzyme Sits at Each
27.5 How Is Metabolism Integrated in a Multicellular Replication Fork 988
Organism? 962 DNA Polymerase I Removes the RNA Primers and
The Brain Accounts for 20% of the Body’s Oxygen Fills in the Gaps 989
Consumption 963 DNA Polymerase I Also Plays a Role in DNA Double-
Muscle Metabolism Is Fueled by Glucose and Free Fatty Strand Break Repair 989
Acids 963 DNA Ligase Seals the Nicks Between Okazaki
Human Biochemistry: Athletic Performance Enhancement Fragments 990
with Creatine Supplements? 965 DNA Polymerase Is Its Own Proofreader 990
The Heart Prefers Fatty Acids as Fuel 966 DNA Replication Terminates at the Ter Region 990
Adipose Tissue Is Hormonally Active 966 A Deeper Look: A Mechanism for All Polymerases 990
Human Biochemistry: Fat-Free Mice—A Model for DNA Polymerases Are Immobilized in Replication
Diabetes 966 Factories 991
The Liver Is the Body’s Metabolic Processing Center 967 28.3 Why Are There So Many DNA Polymerases? 991
Human Biochemistry: The Metabolic Effects of Alcohol ells Have Different Versions of DNA Polymerase, Each for
C
Consumption 968 a Particular Purpose 991
27.6 What Regulates Our Eating Behavior? 968 The Common Architecture of DNA Polymerases 991
he Hormones That Control Eating Behavior
T 28.4 How Is DNA Replicated in Eukaryotic Cells? 992
Come from Many Different Tissues 969 he Cell Cycle Controls the Timing of DNA Replication 992
T
Ghrelin and Cholecystokinin Are Short-Term Proteins of the Prereplication Complex Are AAA1 ATPase
Regulators of Eating Behavior 970 Family Members 995
Insulin and Leptin Are Long-Term Regulators of Eating Geminin Provides Another Control Over Replication
Behavior 970 Initiation 995
xxiv Detailed Contents
ukaryotic Cells Also Contain a Number of Different DNA

E NA Rearrangements Assemble an H-Chain Gene by
D
Polymerases 995 Combining Four Separate Genes 1021
28.5 How Are the Ends of Chromosomes Replicated? 996 V–J and V–D–J Joining in Light- and Heavy-Chain Gene
Assembly Is Mediated by the RAG Proteins 1022
28.6 How Are RNA Genomes Replicated? 996
Imprecise Joining of Immunoglobulin Genes Creates New
A Deeper Look: RNA as Genetic Material 998
Coding Arrangements 1025
The Enzymatic Activities of Reverse Transcriptases 998
Antibody Diversity Is Due to Immunoglobulin Gene
28.7 How Is the Genetic Information Rearranged Rearrangements 1025
by Genetic Recombination? 999 Foundational Biochemistry 1026
eneral Recombination Requires Breakage and Reunion
G Problems 1027
of DNA Strands 999
Further Reading 1028
Homologous Recombination Proceeds According to the
Holliday Model 1000
The Enzymes of General Recombination Include RecA,
RecBCD, RuvA, RuvB, and RuvC 1000
The RecBCD Enzyme Complex Unwinds dsDNA and
29
Cleaves Its Single Strands 1002 Transcription and the Regulation of Gene
The RecA Protein Can Bind ssDNA and Then Interact with Expression 1033
Duplex DNA 1002
29.1 How Are Genes Transcribed in Bacteria? 1033
RuvA, RuvB, and RuvC Proteins Resolve the Holliday
A Deeper Look: Conventions Used in Expressing the
Junction to Form the Recombination Products 1004
Sequences of Nucleic Acids and Proteins 1034
The Three Rs of Genomic Manipulation: Replication,
Bacterial RNA Polymerases Use Their Sigma Subunits to
Recombination, and Repair 1005
Identify Sites Where Transcription Begins 1034
A Deeper Look: Knockout Mice: A Method to Investigate
The Process of Transcription Has Four Stages 1034
the Biological Role of a Gene 1006
A Deeper Look: DNA Footprinting—Identifying
Homologous Recombination in Eukaryotes Helps to
the Nucleotide Sequence in DNA Where a Protein
Prevent Cancer 1007
Binds 1037
Transposons Are DNA Sequences That Can Move from
Place to Place in the Genome 1007 29.2 How Is Transcription Regulated in Bacteria? 1041
Human Biochemistry: The Breast Cancer Susceptibility ranscription of Operons Is Controlled by
T
Genes BRCA1 and BRCA2 Are Involved in DNA Damage Induction and Repression 1041
Control and DNA Repair 1008 The lac Operon Is a Paradigm of Operons 1042
28.8 Can DNA Be Repaired? 1008 lac Repressor Is a Negative Regulator of the lac
Operon 1043
ouble-Strand DNA Breaks 1009
D
C AP Is a Positive Regulator of the lac Operon 1044
Mismatch Repair Corrects Errors Introduced During DNA
Replication 1012 A Deeper Look: Quantitative Evaluation of lac
Repressor;DNA Interactions 1045
Damage to DNA by UV Light or Chemical Modification
Can Also Be Repaired 1012 Negative and Positive Control Systems
Are Fundamentally Different 1046
A Deeper Look: Transgenic Animals Are Animals
Carrying Foreign Genes 1013 The araBAD Operon Is Both Positively
and Negatively Controlled by AraC 1046
28.9 What Is the Molecular Basis of Mutation? 1014
The trp Operon Is Regulated Through a Co-Repressor–
oint Mutations Arise by Inappropriate Base-Pairing 1015
P Mediated Negative Control Circuit 1048
Mutations Can Be Induced by Base Analogs 1016 Attenuation Is a Prokaryotic Mechanism for Post-
Chemical Mutagens React with the Bases in DNA 1016 Transcriptional Regulation of Gene Expression 1049
Insertions and Deletions 1016 DNA: Protein Interactions and Protein;Protein
28.10 Can Genetic Recombination Create Interactions Are Essential to Transcription
Protein Diversity? 1018 Regulation 1050
ells Active in the Immune Response Are Capable of
C Proteins That Activate Transcription Work Through
Gene Rearrangement 1018 Protein;Protein Contacts with RNA Polymerase 1050
Immunoglobulin G Molecules Contain Regions DNA Looping Allows Multiple DNA-Binding
of Variable Amino Acid Sequence 1018 Proteins to Interact with One Another 1051
The Immunoglobulin Genes Undergo Gene 29.3 How Are Genes Transcribed in Eukaryotes? 1052
Rearrangement 1019 ukaryotes Have Three Classes of RNA Polymerases 1053
E
DNA Rearrangements Assemble an L-Chain Gene by RNA Polymerase II Transcribes Protein-Coding
Combining Three Separate Genes 1021 Genes 1053
Detailed Contents xxv
he Regulation of Gene Expression Is More Complex in

T 29.6 Can Gene Expression Be Regulated Once the
Eukaryotes 1055 Transcript Has Been Synthesized? 1077
Gene Regulatory Sequences in Eukaryotes Include iRNAs Are Key Regulators in Post-Transcriptional Gene
m
Promoters, Enhancers, Insulators, and Silencers 1055 Regulation 1077
Transcription Initiation by RNA Polymerase II Requires Targeted RNA Degradation by Exosomes 1079
TBP and the GTFs 1057
29.7 Can We Propose a Unified Theory of Gene
The Role of Mediator in Transcription Activation and Expression? 1080
Repression 1058
Mediator as a Repressor of Transcription 1060
Problems 1082
Chromatin-Remodeling Complexes and Histone-
Modifying Enzymes Alleviate the Repression Due to Further Reading 1084
Nucleosomes 1060
Chromatin-Remodeling Complexes Are Nucleic
Acid–Stimulated Multisubunit ATPases 1061
Covalent Modification of Histones 1061
30
Covalent Modification of Histones Suggests Protein Synthesis 1089
the Existence of a Histone Code 1062
30.1 What Is the Genetic Code? 1090
Methylation and Phosphorylation Act as a Binary
The Genetic Code Is a Triplet Code 1090
Switch that Regulates Chromatin Dynamics 1062
Codons Specify Amino Acids 1090
Chromatin Deacetylation Leads to Transcription
A Deeper Look: Natural and Unnatural Variations in the
Repression 1063
Standard Genetic Code 1092
Nucleosome Alteration and Interaction of RNA
Polymerase II with the Promoter Are Essential Features in 30.2 How Is an Amino Acid Matched
Eukaryotic Gene Activation 1063 with Its Proper tRNA? 1092
29.4 How Do Gene Regulatory Proteins Recognize Specific minoacyl-tRNA Synthetases Interpret the Second
A
Genetic Code 1093
DNA Sequences? 1064
Evolution Has Provided Two Distinct Classes of
Human Biochemistry: Storage of Long-Term Memory
Aminoacyl-tRNA Synthetases 1093
Depends on Gene Expression Activated by
CREB-Type Transcription Factors 1065 Aminoacyl-tRNA Synthetases Can Discriminate Between
the Various tRNAs 1095
a-Helices Fit Snugly into the Major Groove of
B-DNA 1065 Escherichia coli Glutaminyl-tRNAGln Synthetase
Recognizes Specific Sites on tRNAGln 1096
Proteins with the Helix-Turn-Helix Motif Use One Helix
to Recognize DNA 1065 The Identity Elements Recognized by Some Aminoacyl-
tRNA Synthetases Reside in the Anticodon 1097
Some Proteins Bind to DNA via Zn-Finger Motifs 1066
A Single G;U Base Pair Defines tRNA Alas 1097
Some DNA-Binding Proteins Use a Basic
Region-Leucine Zipper (bZIP) Motif 1067 30.3 What Are the Rules in Codon–Anticodon Pairing? 1098
29.5 How Are Eukaryotic Transcripts Processed and rancis Crick Proposed the Wobble Hypothesis for
F
Delivered to the Ribosomes for Translation? 1068 Codon–Anticodon Pairing 1098
ukaryotic Genes Are Split Genes 1068
E Some Codons Are Used More Than Others 1098
The Organization of Exons and Introns in Split Nonsense Suppression Occurs When Suppressor tRNAs
Genes Is Both Diverse and Conserved 1069 Read Nonsense Codons 1100
Post-Transcriptional Processing of Messenger RNA 30.4 What Is the Structure of Ribosomes,
Precursors Involves Capping, Methylation, and How Are They Assembled? 1100
Polyadenylylation, and Splicing 1069 rokaryotic Ribosomes Are Composed of 30S and 50S
P
Nuclear Pre-mRNA Splicing 1072 Subunits 1100
The Splicing Reaction Proceeds via Formation of a Lariat Ribosomes Spontaneously Self-Assemble In Vitro 1102
Intermediate 1072 Ribosomes Have a Characteristic Anatomy 1102
Splicing Depends on snRNPs 1073 The Cytosolic Ribosomes of Eukaryotes Are Larger Than
snRNPs Form the Spliceosome 1073 Prokaryotic Ribosomes 1103
Alternative RNA Splicing Creates Protein Isoforms 1074 30.5 What Are the Mechanics of mRNA Translation? 1104
A Deeper Look: Inteins—Bizarre Parasitic Genetic ranslation Can be Organized into Three Steps: Initiation,
T
Elements Encoding a Protein-Splicing Activity 1075 Elongation, and Termination 1104
RNA Editing: Another Mechanism That Increases Peptide Chain Initiation in Bacteria Requires a G-Protein
the Diversity of Genomic Information 1076 Family Member 1105
xxvi Detailed Contents
eptide Chain Elongation Requires Two G-Protein Family

P A Deeper Look: Chaperone Proteins That Function by
Members 1107 Stress-Induced Unfolding 1138
The Elongation Cycle 1107 A Deeper Look: Small Heat Shock Proteins: Nature’s
Aminoacyl-tRNA Binding and the Peptidyl Transferase Molecular Sponges 1140
Reaction 1108 31.2 How Are Proteins Processed Following
GTP Hydrolysis Fuels the Conformational Changes That Translation? 1141
Drive Ribosomal Functions 1112
31.3 How Do Protein Translocation Pathways Target Pro-
A Deeper Look: Molecular Mimicry—The Structures of teins to Subcellular Compartments? 1142
EF-Tu: Aminoacyl-tRNA, EF-G, and RF-3 1112
roteins Are Delivered to the Proper Cellular
P
Peptide Chain Termination Requires Yet Another Compartment by Translocation 1142
G-Protein Family Member 1113
The SecYEG Translocon Mediates Translocation of Newly
The Ribosomal Subunits Cycle Between 70S Complexes Synthesized Prokaryotic Proteins 1143
and a Pool of Free Subunits 1113
The Sec61 Translocon Mediates Translocation of Newly
A Deeper Look: Tethered Ribosomes Open New Synthesized Eukaryotic Proteins 1144
Possibilities in Synthetic Biology 1115
Human Biochemistry: Autophagy—How Cells Recycle
Polyribosomes Are the Active Structures of Protein Their Materials 1146
Synthesis 1116
31.4 How Does Protein Degradation Regulate Cellular
30.6 How Are Proteins Synthesized in Eukaryotic
Levels of Specific Proteins? 1147
Cells? 1116
ukaryotic Proteins Are Targeted for Proteasome
E
Peptide Chain Initiation in Eukaryotes 1116 Destruction by the Ubiquitin Pathway 1147
Control of Eukaryotic Peptide Chain Initiation Is One Proteins Targeted for Destruction Are Degraded by
Mechanism for Post-Transcriptional Regulation of Gene Proteasomes 1149
Expression 1118
Small Ubiquitin-like Protein Modifiers Are Post-
Peptide Chain Elongation in Eukaryotes Resembles the transcriptional Regulators 1151
Prokaryotic Process 1120
HtrA Proteases Also Function in Protein Quality
Human Biochemistry: Diphtheria Toxin ADP-Ribosylates Control 1153
eEF2 1120
Human Biochemistry: Proteasome Inhibitors in Cancer
Eukaryotic Peptide Chain Termination Requires eRF1, Chemotherapy 1154
eRF3, and GTP 1121
Protein Triage—A Model for Quality Control 1155
30.7 Do Protein Synthesis Inhibitors Have Clinical
Applications? 1121
Problems 1156
The Decoding Site Is a Target of Aminoglycoside
Antibiotics 1121 Further Reading 1157
Many Antibiotics Target the PTC and the Peptide Exit
Tunnel 1122
Eukaryotic-Specific Protein Synthesis Inhibitors 1124
32
Problems 1125 The Reception and Transmission of Extracellular
Further Reading 1127 Information 1161
32.1 What Are Hormones? 1163
31 teroid Hormones Act in the Nucleus or at the

S
Plasma Membrane 1163
Polypeptide Hormones Share Similarities
Completing the Protein Life Cycle: Folding, of Synthesis and Processing 1163
Processing, and Degradation 1131 32.2 What Is Signal Transduction? 1164

Many Signaling Pathways Involve Enzyme Cascades 1165
31.1 How Do Newly Synthesized Proteins Fold? 1132
Signaling Pathways Connect Membrane Interactions
Human Biochemistry: Neurodegenerative Disorders are
with Events in the Nucleus 1165
Caused by the Accumulation of Protein Deposits 1133
Signaling Pathways Depend on Multiple Molecular
Chaperones Help Some Proteins Fold 1134
Interactions 1165
Hsp70 Chaperones Bind to Hydrophobic Regions of
Extended Polypeptides 1134 32.3 How Do Signal-Transducing Receptors Respond
to the Hormonal Message? 1168
Hsp90 Partners With Hsp70 in Hsp70-Hsp90 Folding
Cascades 1136 he G-Protein–Coupled Receptors Are 7-TMS Integral
T
Membrane Proteins 1168
The GroES–GroEL Complex of E. coli Is an Hsp60
Chaperonin 1137 The Single TMS Receptors Are Guanylyl Cyclases
or Tyrosine Kinases 1170
Detailed Contents xxvii
RTKs and RGCs Are Membrane-Associated Allosteric G-Protein Signaling Is Modulated by RGS/GAPs 1192
Enzymes 1170 GPCR Desensitization Leads to New Signaling
The EGF Receptor Is Activated by Ligand-Induced Pathways 1192
Dimerization 1170 A Deeper Look: Whimsical Names for Proteins and
The Insulin Receptor Mediates Several Signaling Genes 1196
Pathways 1173 Receptor Responses Can Be Coordinated by
Receptor Guanylyl Cyclases Mediate Effects Transactivation 1196
of Natriuretic Hormones 1175 Signals from Multiple Pathways Can Be Integrated 1196
Nonreceptor Tyrosine Kinases Are Typified by 32.7 How Do Neurotransmission Pathways Control
pp60src 1177
the Function of Sensory Systems? 1198
A Deeper Look: Nitric Oxide, Nitroglycerin, and Alfred
Nerve Impulses Are Carried by Neurons 1198
Nobel 1178
Ion Gradients Are the Source of Electrical Potentials in
Soluble Guanylyl Cyclases Are Receptors for Nitric
Neurons 1198
Oxide 1179
Action Potentials Carry the Neural Message 1199
32.4 How Are Receptor Signals Transduced? 1179
The Action Potential Is Mediated by the Flow of Na1 and
GPCR Signals Are Transduced by G Proteins 1179 K1 Ions 1200
Cyclic AMP Is a Second Messenger 1180 Neurons Communicate at the Synapse 1201
Ras and Other Small GTP-Binding Proteins Are Communication at Cholinergic Synapses Depends upon
Proto-Oncogene Products 1181 Acetylcholine 1202
G Proteins Are Universal Signal Transducers 1182 There Are Two Classes of Acetylcholine Receptors 1202
Specific Phospholipases Release Second Amino Acids, Catecholamines, and Peptides Can Act as
Messengers 1183 Neurotransmitters within Synaptic Junctions 1204
Human Biochemistry: Cancer, Oncogenes, and Tumor Glutamate and Aspartate Are Excitatory Amino Acid
Suppressor Genes 1185 Neurotransmitters 1205
Lipids Such as Phosphatidylcholine, Sphingomyelin, A Deeper Look: Tetrodotoxin and Saxitoxin Are Na1
Glycosphingolipids, and Arachidonic Acid Also Generate Channel Toxins 1206
Second Messengers 1185
Human Biochemistry: Neurexins and Neuroligins—the
Calcium Is a Second Messenger 1186 Scaffolding of Learning and Memory 1207
Calmodulin Target Proteins Possess a Basic Amphiphilic g-Aminobutyric Acid and Glycine Are Inhibitory
Helix 1186 Neurotransmitters 1208
Human Biochemistry: PI Metabolism and the Human Biochemistry: The Biochemistry of Neurological
Pharmacology of Li1 1186 Disorders 1210
32.5 How Do Effectors Convert the Signals to Actions The Catecholamine Neurotransmitters Are Derived from
in the Cell? 1188 Tyrosine 1212
Protein Kinase A Is a Paradigm of Kinases 1188 Various Peptides Also Act as Neurotransmitters 1212
A Deeper Look: Mitogen-Activated Protein Kinases and Some Ion Channels Respond to Physical Stimuli Rather
Phosphorelay Systems 1189 Than Chemicals 1213
Protein Kinase C Is a Family of Isozymes 1189 Foundational Biochemistry 1214
Protein Tyrosine Kinase pp60 c-src Is Regulated Problems 1214
by Phosphorylation/Dephosphorylation 1190
Further Reading 1216
Protein Tyrosine Phosphatase SHP-2 Is a Nonreceptor
Tyrosine Phosphatase 1190 Abbreviated Answers to Problems A-1
32.6 How Are Signaling Pathways Organized and
Index I-1
Integrated? 1191
GPCRs Can Signal Through G-Protein–Independent
Pathways 1191
Careers in Chemistry
Chapter 1: Michelle Nguyen, Compliance and Integrity Officer at Nationwide Children’s Hospital 9
Chapter 2: Kilan C. Ashad-Bishop, Biomedical Scientist and Advocate at Sylvester Comprehensive Cancer Center 32
Chapter 3: (Chemistry in History) Satoshi Ōmura, 2015 Nobel Prize Winner in Physiology or Medicine for his studies on novel
therapies against infections caused by roundworm parasites 53
Chapter 4: Vanessa A. Nadal, Professor of Law at Fordham University and co-creator of first U.S. Cosmetics Regulation course 78
Chapter 5: Lilla Morton, Biochemistry Teacher at Zayed Private Academy 106
Chapter 6: (Chemistry in History) César Milstein, 1984 Novel Prize Winner for Physiology or Medicine for his studies on monoclonal
antibodies 147
Chapter 7: Dr. Shannon Timmons, Professor and Chair of the Natural Sciences Department at Lawrence Technological University 194
Chapter 8: (Chemistry in History) Alice Ball, creator of the “Ball Method” as a treatment for leprosy in the early 20th century 240
Chapter 9: Dr. Audie Thompson, Assistant Professor of Chemical Engineering at the University of Arkansas 267
Chapter 10: Phillip Nega, researcher in solid-state battery technology at A123 Systems 325
Chapter 11: Sabrina Farais, lab director with the Oklahoma Medical Marijuana Authority (OMMA) 348
Chapter 12: (Chemistry in History) Tu Youyou, 2015 Nobel Prize winner in Physiology or Medicine for her discoveries of novel therapies
against malaria 394
Chapter 13: (Chemistry in History) Maud Menten, co-creator of the Michaelis-Menten equation which relates the rate of an enzyme-
catalyzed reaction to the enzyme’s affinity for its substrate 434
Chapter 14: (Chemistry in History) Dr. John Cornforth, 1975 Nobel Prize Winner in Chemistry for his studies of the stereochemistry of
enzymes involved in cholesterol biosynthesis 483
Chapter 15: Dr. Cierra Smith, Manager of Diversity, Equity, and Inclusion (DEI) Programs for the American Society of Biochemistry and
Molecular Biology (ASBMB) 512
Chapter 16: Dr. Enrique M. De La Cruz, Professor and Chair of Molecular Biophysics and Biochemistry at Yale University 548
Chapter 17: (Chemistry in History) Dr. Marie Maynard Daly, responsible for the earliest research on the relationship between diet,
blood cholesterol, and heart health 580
Chapter 18: Neem J. Patel, Ph.D. candidate at the University of California studying soil recovery after forest fires. 606
Chapter 19: Rochelle Diamond, Manager of the Flow Cytometry/Cell Sorting Facility at the California Institute of Technology and
founder of Out to Innovate 637
Chapter 20: Dr. Vincent Wu, research scientist at Triplebar engineering fungi to produce bovine milk proteins 674
Chapter 21: (Chemistry in History) Dr. Emmett Chapelle, inventor of method for the detection of ATP used today for detection of
microbes in food and water 720
Chapter 22: Dr. Kayunta Johnson-Winters, Associate Professor at the University of Texas at Arlington with research focused on F420-
dependent enzymes. 753
Chapter 23: Dr. Katherine Scheibel, subject matter expert for Cengage Academic Publishing
Chapter 24: (Chemistry in History) Dr. Konard Emil Bloch, 1964 Nobel Prize winner in Physiology or Medicine for his studies of
cholesterol and fatty acid metabolism
Chapter 25: Dr. Squire J. Booker, Evan Push Professor of Chemistry, Biochemistry, and Molecular Biology as well as the Eberly
Distinguished Chair in Science at Pennsylvania State University 876
Chapter 26: Dr. Allison C. Augustus-Wallace, Associate Professor and Director of Undergraduate Academic Pathway Programs for
Diversity at LSU Health Sciences Center-New Orleans 927
Chapter 27: Dr. James M. Ntambi, Professor at the University of Wisconsin-Madison and winner of the American Society for
Biochemistry and Molecular Biology Award for Exemplary Contributions to Education
xxviii
Careers in Chemistry xxix
Chapter 28: (Chemistry in History) Dr. Slayton A. Evans, Jr., First African-American Assistant Professor of Chemistry at University of
North Carolina-Chapel Hill and committee chair for the American Chemistry Society, the National Institutes of Health, and
the National Science Foundation 983
Chapter 29: Dr. Elsa Pao, Optometrist with her own private practice 1038
Chapter 30: Dr. Alison Brown, Program Director for the National Institutes of Health’s National Heart, Blood, and Lung Institute 1091
Chapter 31: Dr. Odutayo (Tayo) Odunuga, Professor of Biochemistry at Stephen F. Austin State University 1135
Chapter 32: Dr. Shantá D. Hinton, Associate Professor and Chair of Biology at the College of William and Mary 1164
PSAFE (Protein Structure and Function
Exploration)
A Resource for Biochemistry Students and Instructors
The Protein Structure and Function Exploration (PSAFE) project* http://psafeonline.
net at the University of Virginia was created as a semester-long project for biochemistry
students to explore structure−function relationships in macromolecules and to research
and write about their findings. Students doing the PSAFE project use the molecular-
document capability of the ICM Browser (from Molsoft LLC) to accomplish their goals.
In this exercise, each student progresses through tutorials about the basics of biomolecular
structure to individual in-depth analysis of a chosen macromolecule and how it achieves its
function. The project culminates in each student creating an interactive graphical display
and accompanying narrative describing the chosen macromolecule’s structure-function
relationships, together with relevant references. These student creations are reviewed and
edited before posting to an archival website (http://psafeonline.net). The PSAFE archive
contains descriptions of well over 1300 different proteins and nucleic acids and is available
to anyone with an interest in exploring structure-function relationships in macromolecules.
This semester-long research and writing project has been added to the Biochemistry 7e,
online course to provide students with the opportunity to explore the structure and func-
tion of an assigned protein. The project culminates in the composition of an interactive
narrative describing the macromolecule’s structure and function.
*Magnotti, E., Moy, J., Sleppy, R., Carey, A., Firdyiwek, Y., Garrett, R. H., and Grisham,
C., 2019. ‘‘Developing and Implementing a Free Online Protein Structure and Function
Exploration Project to Teach Undergraduate Students Macromolecular Structure−Function
Relationships.’’ Journal of Chemical Education 96:729–733.
xxx
Laboratory Techniques in Biochemistry
All of our knowledge of biochemistry is the outcome of experiments. For the most part,
this text presents biochemical knowledge as established fact, but students should never lose
sight of the obligatory connection between scientific knowledge and its validation by obser-
vation and analysis. The path of discovery by experimental research is often indirect, tortu-
ous, and confounding before the truth is realized. Laboratory techniques lie at the heart of
scientific inquiry, and many techniques of biochemistry are presented within these pages to
foster a deeper understanding of the biochemical principles and concepts that they reveal.
Recombinant DNA Techniques Fluxomics Section 17.5

Restriction endonuclease digestion of DNA Section 10.6d Tumor diagnosis with positron emission tomography (PET) Section 18.7
Restriction mapping Section 10.6e–f Glucose monitoring devices Section 22.1
DNA sequencing Section 11.1 Fluoro-substituted analogs as therapeutic agents Section 26.8
Nucleic acid hybridization Section 11.3 “Knockout” mice Section 28.7
Chemical synthesis of nucleic acids Section 11.6
Isolation/Purification of Macromolecules
Cloning; recombinant DNA constructions Section 12.1
Construction of genomic DNA libraries Section 12.2 Ion exchange chromatography Section 5.2
Combinatorial libraries of synthetic oligomers Section 12.2 Protein purification protocols Section 5.2
Screening DNA libraries by colony hybridization Section 12.2b Dialysis and ultrafiltration Section 5.2
PCR (polymerase chain reaction) Section 12.2d Size exclusion chromatography Section 5.2
mRNA isolation Section 12.2e SDS-polyacrylamide gel electrophoresis Section 5.2
Construction of cDNA libraries Section 12.2e Isoelectric focusing Section 5.2
Expressed sequence tags (ESTs) Section 12.2e Two-dimensional gel electrophoresis Section 5.2
Southern blotting Section 12.2d Hydrophobic interaction chromatography Section 5.2
Gene chips (DNA microarrays) Section 12.2f High-performance liquid chromatography Section 5.2
Protein expression from cDNA inserts Section 12.3 Affinity chromatography Section 5.2
Screening protein expression libraries with antibodies Section 12.3a Ultracentrifugation Section 5.2
Two-hybrid systems to identify protein-protein interactions Section 12.3c Fractionation of cell extracts by centrifugation Section 5.2
Reporter gene constructs Section 12.3b Proteomic analysis by multidimensional protein identification
RT-qPCR (real-time quantitative PCR) Section 12.3a technology Section 5.8b
In vitro mutagenesis Section 12.3d
ChIP-Seq (chromatin immunoprecipitation-DNA sequencing) Section 12.3c Analyzing the Physical and Chemical Properties
RNAi Section 12.4 of Biomolecules
Genome editing with CRISPR-Cas9 Section 12.5d Titration of weak acids Section 2.2b
Base editing with CRISPR-Cas9 Section 12.5e Preparation of buffers Section 2.3
Prime editing with CRISPR-Cas9 Section 12.5f Measurement of standard reduction potentials Section 3.6
Gene silencing with CRISPR-Cas9 Section 12.5g
Edman degradation Section 4.3
High-throughput screening Section 12.6
Nuclear magnetic resonance (NMR) Sections 4.5 and 6.4
BioBricks Section 12.7a
Estimation of protein concentration Section 5.2
CRISPR/Cas9 Section 12.5
Amino acid analysis Section 4.6
Probing the Function of Biomolecules Amino acid sequence determination Section 5.3
Green fluorescent protein Section 4.4 Mass spectrometry of proteins Section 5.3i
Plotting enzyme kinetic data Section 13.3j Solid-phase peptide synthesis Section 5.5
Enzyme inhibition Section 13.4 Cryo-Electron Microscopy Section 6.4
Isotopic tracers as molecular probes Section 17.4c Membrane lipid phase transitions Section 9.4b
RNAi Section 12.4 Nucleic acid hydrolysis Section 10.6
NMR spectroscopy Section 17.4d DNA sequencing Section 11.1
Transgenic animals Section 28.8 Single-molecule DNA sequencing Section 11.1e,f
DNA footprinting Section 29.1 Density gradient (isopycnic) centrifugation Section 11.3
Techniques Relevant to Clinical Biochemistry
Human gene therapy Section 12.5
Metabolomic analysis Section 17.5 xxxi
Preface
Biochemistry
Scientific understanding of the molecular nature of life is growing at an astounding rate.
Significantly, society is the prime beneficiary of this increased understanding. Cures
for diseases, better public health, remedies for environmental pollution, and the devel-
opment of cheaper and safer natural products are just a few practical benefits of this
knowledge. In addition, this expansion of information fuels, in the words of Thomas
Jefferson, “the illimitable freedom of the human mind.” Scientists can use the tools of
biochemistry and molecular biology to explore all aspects of an organism—from basic
questions about its chemical composition, through inquiries into the complexities of its
metabolism, differentiation, and development, to analysis of its evolution, and even its
behavior. New procedures based on the results of these explorations lie at the heart of
the many modern medical miracles. Biochemistry is a science whose boundaries now
encompass all aspects of biology, from molecules to cells, to organisms, to ecology, and
to all aspects of health care. This seventh edition of Biochemistry embodies and reflects
the expanse of this knowledge. We hope that this new edition will encourage students to
ask questions of their own and to push the boundaries of their curiosity about science.
Making Connections
As the explication of natural phenomena rests more and more on biochemistry, its inclu-
sion in undergraduate and graduate curricula in biology, chemistry, and the health sci-
ences becomes imperative. The challenge to authors and instructors is a formidable one:
how to familiarize students with the essential features of modern biochemistry in an
introductory course or textbook. Fortunately, the increased scope of knowledge allows
scientists to make generalizations connecting the biochemical properties of living sys-
tems with the character of their constituent molecules. As a consequence, these general-
izations, validated by numerous examples, emerge in time as principles of biochemistry,
principles that are useful in discerning and describing new relationships between diverse
biomolecular functions and in predicting the mechanisms underlying newly discovered
biomolecular processes. Nevertheless, it is increasingly apparent that students must
develop skills in inquiry-based learning, so that beyond this first encounter with bio-
chemical principles and concepts students are equipped to explore science on their own.
Much of the design of this new edition is meant to foster the development of such skills.
We are both biochemists, but one of us spent his career in a biology department, and
the other in a chemistry department. Undoubtedly, we each view biochemistry through
the lens of our respective disciplines. We believe, however, that our collaboration on this
textbook represents a melding of our perspectives that will provide new dimensions of
appreciation and understanding for all students.
xxxii
Preface xxxiii
Our Audience
This biochemistry textbook is designed to communicate the fundamental principles
upon which all life is based to students encountering biochemistry for the first time. We
aim to bring an appreciation of biochemistry to a broad audience that includes under-
graduates majoring in the life sciences, physical sciences, or premedical programs as well
as medical students and graduate students in the various health sciences for whom bio-
chemistry is an important route to understanding human physiology. To make this sub-
ject matter more relevant and interesting to all readers, we emphasize, where appropriate,
the biochemistry of humans.
Objectives and Building on Previous Editions

We carry forward the clarity of purpose found in previous editions; namely, to
illuminate for students the principles governing the structure, function, and interactions
of biological molecules. At the same time, this new edition has been revised to reflect
tremendous developments in biochemistry. Significantly, emphasis is placed on the
interrelationships of ideas so that students can begin to appreciate the overarching
questions of biochemistry.
New Features
New Textbook Features
●● Think-Pair-Share Problems in every chapter encourage students to work collabora-
tively to further their understanding of biochemistry concepts.
●● Careers in Chemistry showcase various career paths that students can take after study-
ing biochemistry. By seeing a diverse, inclusive, and equitable chemical community, all
students know that they have a future in chemistry-related careers.
●● Over 160 New and Revised Exercises were added to the book and online course to
keep the content current.
●● Step-by-Step Solutions were added to examples to help students master the approach
to complicated problems.
●● Recent Developments in Biochemistry: A number of Deeper Look and Critical Develop-
ments in Biochemistry boxes were added to address the latest developments in biochem-
istry such as the human proteome, NMR and Cryo-EM, AlfaFold, and CRISPR-Cas9.
New to the Online Course and Resources

●● MCAT Essays and Practice Problems accompanied by detailed answer explanations,
written by members of medical school admissions and advisors, have been added to
the online course in OWLv2 to prepare students for the biochemistry section of the
MCAT exam.
●● Hints and Targeted Feedback. Over fifty percent of problems in OWLv2 now come
with targeted feedback on common errors that students make. The targeted feed-
back explains why the student's answer is incorrect and guides them toward a correct
solution.
●● Laddered Assessments. Conceptual mastery modules are combined with more tradi-
tional homework questions into one structured learning path, organized by topic at
the chapter level.
●● Over 300 New Problems were added to the online course.
●● PSAFE: Protein Structure and Function Exploration Project. Students research a protein
and use protein-modeling software to practice biochemistry actively in this research
and writing semester-long project.
●● Protein Structure and Function Exploration Library of Proteins and Nucleic Acids is an
online resource (http://www.psafeonline.net/) of over 1300 protein and nucleic acid
animations and interactive views, sorted by proteins and chapters in this textbook.
xxxiv Preface
New to this Edition

Chapter 3 A new Deeper Look box called “Why Nature Chose Phosphates.”
Chapter 4 A new Deeper Look box called “Why Nature Chose Selenium,” and a revised
Critical Developments in Biochemistry box on the incorporation of unnatural amino
acids into proteins.
Chapter 5 A new exercise on determining amino-acid sequence from mass spectrometry
data. Efforts to describe the human proteome are introduced in a new Deeper Look box:
“The Human Proteome Project and the Human Protein Atlas.”
Chapter 6 A new Critical Developments in Biochemistry box on the X-ray crystallography
of proteins and a revised Deeper Look feature on metamorphic proteins, which exist as
an ensemble of structures of similar energies and stabilities. New Critical Developments
in Biochemistry boxes on the Protein Data Bank (PDB) and “NMR and Cryo-EM —
Revolutionary Methods that Probe Protein Structure and Dynamics” (including
cryo-EM structure of the 2P spike protein mutant related to development of COVID-
19 vaccines). New coverage of AlphaFold, artificial intelligence software that accurately
predicts the three-dimensional structures of proteins based solely on their amino acid
sequences.
Chapter 8 A new Human Biochemistry box on the development of vaccines for
COVID-19 that employ lipid nanoparticles and make RNA vaccines practical and
effective.
Chapter 9 New coverage of monotopic, bitopic, and polytopic membrane proteins and
a section called “Dynamic Exchange of Lipids and Proteins with Membrane Domains.”
Chapter 10 An updated introduction to the many roles of small RNAs in the regulation
of gene expression: miRNAs and the long, noncoding RNAs (lincRNAs).
Chapter 11 Completion of the complete nucleotide sequence determination for the human
genome in 2022. Focus on the rapidly growing science of bioinformatics: the study of the
nature and organization of biological information, including functional genomics and
proteomics. New principles emerging about the higher order structural organization of
chromosomes, chromosome territories, and chromosome dynamics. Synthetic chromo-
somes, DNA as a data storage medium.
Chapter 12 Genome engineering with CRISPR-Cas9, CRISPR-Cas9 in gene-editing and
base-editing. A new section on human gene therapy, rewriting the human genome.
Chapter 14 A new Critical Developments in Biochemistry box on Nobel laureate Frances
Arnold and her pioneering work on the directed evolution of enzymes.
Chapter 17 Metabolites at the center of life, metabolomics as the driver of all the
other –omics.
Chapter 18 The newly-discovered protein kinase activity of protein kinase M2 (PK M2),
its stimulation by SAICAR (an intermediate in the purine biosynthetic pathway), and its
role in tumor proliferation.
Chapter 20 The new molecular structures of the supercomplexes that carry out electron
transport and oxidative phosphorylation, including the new structure of Complex I and
insights regarding its mechanism of action.
Chapter 22 A new Human Biochemistry box called “Metformin — A Diabetes Drug
with Multiple Actions,” and a Critical Developments in Biochemistry feature describing
how the consumption of ATP promotes and supports the metabolism of cancer cells.
Chapter 25 Synthesis of cysteine in humans by a reverse transsulfurylation pathway.
A new Human Biochemistry box on amino acid metabolism and cancer.
Chapter 26 Figure describing the purinosome metabolon that synthesizes purines on a
PRPP platform.
Preface xxxv
Chapter 27 New molecular graphic of mTORC1, the master integrator of information

about nutrient status and a global regulator of biosynthesis. A new section on AMPK
inhibition of mTORC1 through reversible phosphorylation. A new section on SIRT1,
mTORC1, AMPK, caloric restriction, and metabolic syndrome.
Chapter 28 New discussion and figure illustrating that DNA polymerases are immo-
bilized within replication factories. New figure showing the structural organization of
eukaryotic DNA replicons.
Chapter 29 Updated discussion of eukaryotic gene regulatory sequences such as promot-
ers, enhancers, insulators, and silencers.
Chapter 30 Pyrrolysine as the twenty-second amino acid. New art illustrating the richly
detailed events in eukaryotic translation initiation.
Chapter 31 New structures of the SecY channel and the SecA ATPase, and cryo-EM
structures of co-translational and post-translational states of the Sec61 translocon com-
plex. New cryo-EM structures of a cullin-RING-UBE2D ubiquitin ligation assembly.
Chapter 32 New cryo-EM structure of the neurotensin receptor-arrestin2 complex. New
section on ion channels that respond to physical stimuli (including temperature, voltage,
pH, redox status, and mechanical phenomena) rather than chemical signals.
Features
●● Clarity of Instruction This edition was re-organized for increased clarity and readability.
Many of the lengthier figure legends were shortened and more information was
included directly within illustrations. These changes will help the more visual reader.
●● Visual Instruction The richness of the Protein Data Bank (www.pdb.org) and avail-
ability of molecular graphics software has been exploited to enliven this text. Over
1100 images of prominent proteins and nucleic acids involved with essential biologi-
cal functions illustrate and inform the subject matter and were prepared especially for
this book.
●● Essential Questions Organization Each chapter in this book is framed around an
Essential Question that invites students to become actively engaged in their learning
and encourages curiosity and imagination about the subject matter. For example, the
Essential Question of Chapter 3 asks, “What are the laws and principles of thermody-
namics that allow us to describe the flows and interchanges of heat, energy, and mat-
ter in biochemical systems?” The section heads then pose Key Questions that serve as
organizing principles for a lecture such as, “What is the daily human requirement for
ATP?” The subheadings are designed to be concept statements that respond to the
section headings.
●● Foundational Biochemistry At the end of each chapter, this feature provides a com-
prehensive list of the principal facts and concepts that a student should understand
after reading each chapter. Presented as short statements or descriptive phrases, the
items in the Foundational Biochemistry list serve as guides to students of the knowl-
edge they have acquired from the chapter and as checklists the students can review in
assessing their learning.
●● End-of-Chapter Problems More than 700 end-of-chapter problems are provided.
They serve as meaningful exercises that help students develop problem-solving
skills useful in achieving their learning goals. Some problems require students to
employ calculations to find mathematical answers to relevant structural or functional
questions. Other questions address conceptual problems whose answers require appli-
cation and integration of ideas and concepts introduced in the chapter.
●● Think-Pair-Share problems encourage students to work collaboratively to further their
understanding.
●● Further Readings sections at the end of each chapter make it easy for students to find
up-to-date additional information about each topic.
xxxvi Preface
●● Critical Developments in Biochemistry essays emphasize recent and historical advances

in the field.
●● Human Biochemistry essays emphasize the central role of basic biochemistry in med-
icine and the health sciences. These essays often present clinically important issues
such as diet, diabetes, and cardiovascular health.
●● A Deeper Look essays expand on the text, highlighting selected topics or experimental
observations.
●● Laboratory Techniques The experimental nature of biochemistry is highlighted, and a
list of laboratory techniques found in this book can be seen on page xxxi.
Instructor and Student Resources

Instructor and student resources are available online.
Instructor resources include:
●● Solution and Answer Guide
●● Test Bank
●● Transition Guide from the Sixth Edition to the Seventh Edition
●● Lecture Note PowerPoint slides
●● Image Library slides
●● Guide to Teaching Online
●● Educator’s Guide
Acknowledgments
We are indebted to the many experts in biochemistry and molecular biology who care-
fully reviewed this book at several stages for their outstanding and invaluable advice
on how to construct an effective textbook.
Reviewers for the 7th edition

Bobby Burkes, Grambling State University
Natasha DeVore, Missouri State University
Todd Eckroat, Penn State Behrend
Michael Guy, Northern Kentucky University
Steven Herron, Utah Valley University
Amber Howerton, Nevada State College
Kyoung Nan Kim, University of Colorado, Denver
Steven LaiHing, Oakwood University
Timothy Reichart, Hampden-Sydney College
Stephen Spiro, University of Texas at Dallas
Brent Znosko, Saint Louis University
Lisa Zuraw, The Citadel
We also wish to gratefully acknowledge many other people who assisted and encour-
aged us in this endeavor. Roxanne Wang, our Product Manager for Upper-Level
Chemistry, has brought enthusiasm and an unwavering emphasis on student learning
as the fundamental purpose of our collective enterprise. Meaghan Ford, the Senior
Content Manager for this edition, has kept us focused on the matters at hand, the urgencies
Preface xxxvii
of the schedule, and limits of scale in a textbook’s dimensions. She is truly a colleague
in these endeavors, as is Mona Zeftel, our Learning Designer, whose focus on student
learning and student perceptions provided crucial guiderails for us in keeping the educa-
tion of students uppermost as we created this new edition. We also applaud the unsung
but absolutely indispensable contributions by Maria Lokshin, Ph.D., our Development
Editor. Maria’s editorial grace was precise and immensely helpful. Her writing skills
and scientific acumen made this textbook eminently more readable. The contribution
of new supplementary end-of-chapter problems by Koen Vercruysse of East Tennessee
State University is gratefully acknowledged and appreciated. This book’s design and
layout is the creative result of work by Chris Doughman. If this book has visual
appeal, it is due to Katy Gabel and John Rich, Project Managers at Lumina Datamatics
and their colleagues. The beautiful illustrations that not only decorate this text but also
explain its contents are a testament to a number of important collaborators. Many
colleagues provided original art and graphic images for this book, particularly Professor
Jane Richardson of Duke University. We acknowledge with pleasure the scientific and
artistic contributions of Michal Sabat of the University of Virginia. Michal was the
creator of most of the PyMOL-based molecular graphics in this book. Much of the
visual appeal that you will find in these pages gives testimony to his fine craftsmanship
and his unflagging dedication to our purpose. Tina Chai, B.S. (Chemistry) graduate of
the University of Virginia, his successor and our Molecular Graphics Design specialist,
carried his work further. Elizabeth Magnotti, B.S. (Chemistry) graduate of the University
of Virginia, and Ph.D., Emory University, pioneered the development of the PSAFE
project, a multi-faceted task requiring scientific knowledge and a sense of its importance.
Yitna Firdyiwek was instrumental in the creation of the PSAFE archive site. Celeste
Costa, a current University of Virginia student, prepared content and tutorial videos
for the current PSAFE course. We want to acknowledge P. Kelley, of Philander Smith
College who audited the content for accuracy, Michael Cascio, of Duquesne University
who is writing hints and targeted feedback for new questions for the online course, and
Rochelle Williams, of the ARC Network, who advised on inclusivity and diversity for this
edition. We owe a special thank you to Rosemary Jurbala Grisham, much loved spouse of
Charles and wonderfully tolerant friend of Reg. Also to be acknowledged with love and
pride are Georgia Cobb Garrett, spouse of Reg, and our children, Jeffrey, Randal, and
Robert Garrett, David and Andrew Grisham, and Emily Grisham Cooke.
We hope this seventh edition of our textbook has captured the growing sense of won-
der and imagination that researchers, teachers, and students share as they explore the
ever-changing world of biochemistry.
“Imagination is more important than knowledge. For while knowledge defines all we cur-
rently know and understand, imagination points to all we might yet discover and create.”
—Albert Einstein
Reginald H. Garrett Charles M. Grisham

Charlottesville, VA Ivy, VA
December 2022
The Facts of Life: Chemistry 1 Part I
Molecular
Components
Is the Logic of Biological of Cells
Phenomena “…everything that living things do can be

understood in terms of the jigglings and
wigglings of atoms.”
Richard P. Feynman. Lectures on Physics,
Addison-Wesley, 1963
Marmaduke St. John/Alamy
 A sperm fertilizing an egg.
Essential Question Key Questions

Molecules are lifeless. Yet the properties of living things derive from the properties of 1.1 What Are the Distinctive Properties
molecules. Despite the spectacular diversity of life, the elaborate structure of biological of Living Systems?
molecules, and the complexity of vital mechanisms, are life functions ultimately 1.2 What Kinds of Molecules Are
interpretable in chemical terms? Biomolecules?
1.3 What Is the Structural Organization
of Complex Biomolecules?
M olecules are lifeless. Yet, in appropriate complexity and number, molecules 1.4 How Do the Properties of
Biomolecules Reflect Their Fitness to
compose living things. These living systems are distinct from the inanimate
the Living Condition?
world because they have certain extraordinary properties. They can grow, move,
1.5 What Are the Organization and
p erform the incredible chemistry of metabolism, respond to stimuli from the
Structure of Cells?
environment, and, most significantly, replicate themselves with exceptional fidelity.
1.6 What Are Viruses?
The chemistry of the living cell resembles the chemistry of organic reactions. Indeed,
cellular constituents, or biomolecules, must conform to the chemical and physical
principles that govern all matter. Despite the spectacular diversity of life, the i ntricacy
of biological structures, and the complexity of vital mechanisms, life functions are
interpretable in chemical terms. Chemistry is the logic of biological phenomena. Living
organisms are self-sustaining systems of chemical reactions.
1.1
What Are the Distinctive Properties
of Living Systems?
The most obvious quality of living organisms is that they are complicated and highly
organized (Figure 1.1). For example, organisms large enough to be seen with the naked
eye are composed of many cells, typically of many types. In turn, these cells possess
subcellular structures, called organelles, which are complex assemblies of very large
polymeric molecules, called macromolecules. These macromolecules show an exquisite
2 Chapter 1 The Facts of Life: Chemistry Is the Logic of Biological Phenomena
Science Photo Library/Alamy

Herbert Kehrer/Corbis
(a) (b)
Figure 1.1 (a) Gelada (Theropithecus gelada), a baboon native to the Ethiopian highlands.
(b) Tropical orchid (Masdevallia norops), Ecuador.
degree of organization in their intricate three-dimensional architecture, even though

they are composed of simple sets of chemical building blocks, such as sugars and amino
acids. Indeed, the complex three-dimensional structure of a macromolecule, known as
its conformation, is a consequence of interactions between the monomeric units,
according to their individual chemical properties.
Biological structures serve functional purposes. That is, biological structures play a
role in the organism’s existence. From parts of organisms, such as limbs and organs,
down to the chemical agents of metabolism, such as enzymes and metabolic intermedi-
ates, a biological purpose can be given for each component. In biology, it is always
meaningful to seek the purpose of observed structures, organizations, or patterns; that
is, to ask what functional role they serve within the organism.
Living systems are actively engaged in energy transformations. Maintenance of the
highly organized structure and activity of living systems depends on their ability to
extract energy from the environment. The ultimate source of energy is the sun. Solar
energy flows from photosynthetic organisms (organisms able to capture light energy by
the process of photosynthesis) through food chains to herbivores and ultimately to car-
nivorous predators at the apex of the food pyramid. The biosphere is thus a system
through which energy flows. Organisms capture some of this energy, be it from photo-
synthesis or the metabolism of food, by forming special energized biomolecules. ATP
and NADPH are the two most prominent examples (Figure 1.2). (Commonly used
abbreviations such as ATP and NADPH are defined on the inside back cover of this
book.) ATP and NADPH are energized biomolecules because they represent chemically
useful forms of stored energy. When these molecules react with other molecules in the
cell, the energy released can be used to drive energetically unfavorable processes. That is,
ATP, NADPH, and related compounds are the power sources that drive the energy-
requiring activities of the cell, including biosynthesis, movement, osmotic work against
concentration gradients, and, in special instances, light emission (bioluminescence). The
living state is characterized by the flow of energy through the organism. Only upon death
does an organism reach equilibrium with its inanimate environment. At the expense of
energy flow, the organism can maintain its intricate order and activity far removed from
equilibrium with its surroundings, yet exist in a state of apparent constancy over time.
This state of apparent constancy, or so-called steady state, is actually a very dynamic
condition: Energy and material are consumed by the organism to maintain its stability
Entropy A thermodynamic term used to designate that
and order. In contrast, inanimate matter, as exemplified by the universe in totality, is
amount of energy in a system that is unavailable to do moving to a condition of increasing disorder or, in thermodynamic terms, maximum
work. entropy.
1.1 What Are the Distinctive Properties of Living Systems? 3
NH2 O
H H
N N C NH2
O– O– O–
–O N N
P O P O P OCH2
N
O O CH2
O O O
–O O
H H P O
H H
OH OH O
OH OH NH2
ATP –O P O
N N
O CH2
O N N
OH O
–O P O–
Figure 1.2 ATP and NADPH, two biochemically important O

energy-rich compounds. NADPH
Living systems have a remarkable capacity for self-replication. Generation after

g eneration, organisms reproduce virtually identical copies of themselves. This self-
replication can proceed by a variety of mechanisms, ranging from simple division in
bacteria to sexual reproduction in plants and animals; but in every case, it is characterized
by an astounding degree of fidelity (Figure 1.3). Indeed, if the accuracy of self-replication
Randal H. Garrett
Figure 1.3 Organisms resemble their parents. Orangutan with infant.
4 Chapter 1 The Facts of Life: Chemistry Is the Logic of Biological Phenomena
Figure 1.4 The DNA double helix. Two complementary polynucleotide chains run in opposite direc-
tions and pair through hydrogen bonding between their nitrogenous bases, A with T and C with G.
Note that everywhere there is an A in one strand, the other has a T; everywhere there is a C in one
strand, there is a G in the other. These complementary nucleotide sequences give rise to structural
complementarity.
were significantly greater, the evolution of organisms would be hampered. This is so

because evolution depends upon natural selection operating on individual organisms
that vary slightly in their fitness for the environment. The fidelity of self-replication
resides ultimately in the chemical nature of the genetic material. This substance is
deoxyribonucleic acid, abbreviated as DNA. It consists of a pair of polymeric chains
built using four different monomers known as deoxynucleotides. These four deoxynu-
cleotide building blocks are symbolized by the letters A, C, G, and T. Information is
encoded in each polynucleotide strand in the form of the precise sequence of A, C, G,
and T deoxynucleotides along its length, much as this sentence contains information as
encoded in the letters of the words that compose it. The two deoxynucleotide chains are
In biochemistry and molecular biology, structurally structurally complementary to one another (Figure 1.4) in that everywhere there is an A
complementary means that two structures align and fit in one strand, the other has a T, and everywhere there is a C in one strand, there is a G
together like pieces of a puzzle.
in the other. DNA can generate two identical copies of itself in a rigorously executed
polymerization process whereby each chain is copied precisely, using the information
provided by its complementary strand. This process ensures a faithful reproduction of
the information written by the original polynucleotide strands. In contrast, the mole-
cules of the inanimate world lack this capacity to r eplicate. A crude mechanism of rep-
lication must have existed at life’s origin.
1.2 What Kinds of Molecules Are Biomolecules?

The elemental composition of living matter differs markedly from the relative
abundance of elements in the earth’s crust. Hydrogen (H), oxygen (O), carbon (C),
and nitrogen (N) constitute more than 99% of the atoms in the human body, with
most of the H and O occurring as water, H2O. Oxygen, silicon (Si), aluminum (Al),
and iron (Fe) are the most abundant atoms in the earth’s crust, with hydrogen, car-
bon, and nitrogen being relatively rare (less than 0.2% each). Nitrogen as d initrogen
(N2) is the predominant gas in the atmosphere, and carbon dioxide (CO2) is present
at a level of 0.04%, a small but critical amount. What property unites hydrogen,
oxygen, carbon, and nitrogen and renders these atoms so suitable to the chemistry
of life? It is their ability to form covalent bonds by electron-pair sharing. Further-
more, hydrogen, c arbon, nitrogen, and oxygen are among the lightest elements of
1.3 What Is the Structural Organization of Complex Biomolecules? 5
the periodic table capable of forming such bonds (Figure 1.5). Because the strength Bond
of covalent bonds is inversely proportional to the atomic weights of the atoms Covalent energy
Atoms e– pairing bond (kJ/mol)
involved, hydrogen, carbon, nitrogen, and oxygen form the strongest covalent
bonds. Two other covalent bond-forming elements, phosphorus (as p hosphate H + H H H H H 436
[2OPO322] derivatives) and sulfur, also play important roles in biomolecules.

C + H C H C H 414
1.2a Biomolecules Are Carbon Compounds

C + C C C C C 343
All biomolecules contain carbon. The prevalence of carbon is due to its unparalleled
versatility in forming stable covalent bonds through electron-pair sharing. Carbon
can form up to four such bonds by sharing each of the four electrons in its outer shell C + N C N C N 292
with electrons contributed by other atoms. Atoms commonly found in covalent link-
age to carbon are carbon itself, hydrogen, oxygen, and nitrogen. Hydrogen can form
one such bond by contributing its single electron to the formation of an electron pair. C + O C O C O 351
Oxygen, with two unpaired electrons in its outer shell, can participate in two covalent
bonds, and nitrogen, which has three unshared electrons, can form three such cova-
lent bonds. Furthermore, carbon, nitrogen, and oxygen can share two electron pairs C + C C C C C 615
to form double bonds with one another within biomolecules, a property that enhances
their chemical versatility. Carbon and nitrogen can even share three electron pairs to C + N C N C N 615
form triple bonds.
Two properties of carbon covalent bonds merit particular attention. One is the ability
of carbon to form covalent bonds with itself. The other is the tetrahedral nature of the
C + O C O C O 686
four covalent bonds when carbon atoms form only single bonds. Together these proper- O + O O O O O 142
ties hold the potential for an incredible variety of linear, branched, and cyclic carbon
compounds. This diversity is multiplied further by the possibilities for including nitro- O + O O O O O 402
gen, oxygen, and hydrogen atoms in these compounds (Figure 1.6). We can therefore
envision the ability of carbon to generate complex structures in three dimensions. These N + N N N N N 946
structures, by virtue of appropriately included nitrogen, oxygen, and hydrogen atoms,
can display unique chemistries suitable to the living state. Thus, we may ask, is there any N + H N H N H 393
pattern or underlying organization that brings order to this astounding potentiality?
O + H O H O H 460
Figure 1.5 Covalent bond formation by e2 pair

s haring. The energy necessary to break a bond is given
1.3
What Is the Structural Organization of Complex in kJ/mol.
Biomolecules?
Examination of the chemical composition of cells reveals a dazzling variety of
organic compounds covering chemical dimensions such as length and mass
(Table 1.1). When biomolecules are classified based on size and chemical properties,
an organizational pattern emerges. The biomolecules are built according to a struc-
tural hierarchy: S imple molecules are the units for building complex structures.
The molecular constituents of living matter do not reflect randomly the infinite
possibilities for combining carbon, hydrogen, oxygen, and nitrogen atoms. Instead, only
a limited set of the many possibilities is found, and these collections share certain
properties essential to the living state. The most prominent aspect of biomolecular
organization is that simple molecules are the building blocks for polymers that contain
thousands or even millions of atoms, structures so large that we refer to them as
macromolecules. What properties do these biomolecules possess that make them so Macro - prefix from the Greek “makros” meaning large
appropriate for the condition of life? or long.
1.3a M
etabolites Are Used to Form the Building Blocks
of Macromolecules
The major precursors for the formation of biomolecules are water, carbon dioxide, and
three inorganic nitrogen compounds—ammonium (NH41), nitrate (NO32), and dini-
trogen (N2). Metabolic processes transform these inorganic precursors through ever
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The scene now shifts back to Kashgar, where the Chinese garrison
surrendered and was enrolled in the army of Yakub Beg as “New
Mussulman”; but the Amban, imitating the fine example of his
colleague at Yarkand, blew up himself and his followers in the fort.
Yakub Beg married the beautiful daughter of the Chinese general,
and was much influenced by this wife, who bore him many children.
For a short time it seemed as if all would go well, but the Tunganis
who had surrendered decided on a final bid for power at Yarkand
and treacherously attacked Yakub Beg. Buzurg Khan, too, at this
juncture deserted his general, whose position appeared desperate;
but again Yakub Beg’s remarkable courage saved the situation. He
imposed his will on the Tunganis by attacking and capturing
Yarkand; then, marching on Kashgar, he defeated Buzurg Khan, who
had declared him a rebel. As a sequel to this victory Buzurg Khan
was deposed and finally expelled, and Yakub Beg assumed the
powers of his master. His position was recognized by the Amir of
Bokhara, who in 1866 conferred upon him the title of Atalik Ghazi or
the “Champion Father”; but, on the other hand, he had to reckon with
the constant jealousy and hostility of neighbouring Khokand, which
was continually inflamed by Russia. The capture of Khotan, which
followed in 1867, ended his first successful period of action, during
which, in spite of inadequate means, he had accomplished much.
While Yakub Beg was establishing his power in Kashgar, Yarkand
and Khotan, his chances of success were being increased by events
in the districts to the north of the range. The Taiping rebellion, which
raged from 1850 to 1864, had laid waste the richest provinces of
China. In 1855, apart from this convulsion, a fierce Moslem
insurrection broke out in Yunnan; and in 1862 there was a rebellion
among the Moslems of Shensi and Kansu, which gradually spread
across the desert to the Ili province, where the Tarantchis combined
with the Tunganis against the Chinese authorities. This rebellion was
successful, and Ili was seized in January 1866, when a Tungani-
Tarantchi Government was formed, which remained in power until
the occupation of the province by Russia in 1871.
We now turn to Yakub Beg’s campaigns to the east of Kashgar. The
Tunganis and Khojas of Aksu were not supported to any material
extent from Ili, and he therefore had mainly to deal with an already
defeated force when he commenced operations in 1867. Aksu,
although naturally a strong position, offered but slight resistance, and
the Atalik marched on to Kucha, which he also captured. After
receiving the submission of Karashahr, Turfan, Hami, and Urumchi
he returned in triumph to Kashgar. He subsequently annexed the
upland district of Sarikol, carrying off its inhabitants and filling their
place with Yarkandis and Kirghiz.
It is probable that Yakub Beg was induced to resume operations
against the Tunganis as much by the difficulty of feeding and paying
his army as by ambition. In the autumn of 1869 he passed farther
east to Korla, which fell, and the series of campaigns was continued,
generally with success, until 1873, the Kashgar troops penetrating as
far east as Chightam, a small town to the east of Turfan. Little regard
was paid to the wretched inhabitants, who were plundered without
mercy and sometimes massacred, in accordance with the usual
practice in Central Asia. The Atalik thus achieved military success,
but he failed to organize his conquests against the day when the
slow-moving Chinese Government should attempt to regain its lost
provinces. On the other hand, he probably could not control his
troops, who would have deserted had looting been forbidden. In any
case his constant military successes produced a great impression in
the neighbouring states and spread his fame far and wide.
Yakub Beg’s power was based on a mercenary force which was
remarkable for its heterogeneous composition. Just as his palace,
which was built and organized on the lines of barracks, was full of
cannon of every description, ranging from ancient Chinese pieces to
modern artillery, so his army included men from every neighbouring
province. The most trustworthy and efficient soldiers were
Khokandis, who, being strangers in the land, would naturally be loyal
to their chief and fellow-countryman, whereas the local peasantry
made indifferent fighters. An element numerically important, but for
the most part of untrustworthy quality, was the Tunganis, who served
mainly from fear. There were also a number of Indian and Afghan
adventurers, some of the former being deserters from the Indian
army. The Chinese troops were never used for distant campaigns.
The men above mentioned, who constituted the regular troops, were
divided into mounted infantry, artillery and infantry, the force being
increased by levies of Kirghiz, Dulanis and other irregulars of
doubtful military value. It is now believed that Yakub Beg had never
more than 20,000 trustworthy men in his service, although
exaggerated accounts of his strength were generally credited. His
troops, owing to his somewhat remarkable personality and many
victories, were of better fighting value than those of Khokand and
Bokhara; but, as the event proved, they were unable to cope with
Chinese troops trained on European lines, nor would they have
withstood equal numbers of Russian troops.
His government was based on the Moslem law, and was very
onerous. It must be recollected that he maintained a court and a
large army, mainly at the expense of perhaps a million poverty-
stricken peasants, who, in addition to paying the heavy taxes of
nominally one-tenth of all produce, were ground down by the unjust
tax-collectors until their condition was pitiable. Moreover, he kept a
huge body of town police and also a large force of secret police,
whose united activities must have added considerably to the general
misery. The fact that he was a strong ruler implied the imposition of
heavier burdens on his unhappy subjects. Moreover, during the
period of his rule, trade with China entirely ceased, to the great loss
of the merchants, who had but little commercial intercourse with
Russia or India.
The relations of Yakub Beg with Russia were of primary importance
to him until the Celestial army re-entered Chinese Turkestan, and it
is consequently desirable to summarize them briefly. The Atalik’s
defence of Ak Masjid and his action before Tashkent have already
been mentioned and were not forgotten by the Russians, who in
1866 dismembered Khokand and defeated Bokhara. The
establishment of his power at Kashgar caused the Russians much
anxiety, and their frontier officials were at first instructed not to
recognize Yakub Beg, but, at the same time, to be conciliatory, in the
illusive hope that this line of action would induce the Atalik to make
overtures.
In pursuance of this fatuous policy the Russians requested sanction
to bridge the river Narin and to construct a road to Kashgar; but,
needless to say, these concessions were categorically refused. By
way of marking their displeasure the Muscovites began to construct
a strong fort at Narin; but their hands were tied by attempts on the
part of the Central Asian Khanates to throw off their hated
domination. Yakub Beg, openly at any rate, preserved neutrality, and
for five years the struggle continued, with the result that the Russian
yoke was riveted more firmly than before on Khokand and Bokhara.
To these preoccupations the Atalik probably owed his safety for the
time being, as the construction of Fort Narin was avowedly intended
as a preliminary to an attack on Kashgar, and it appears that an
expedition destined for that task in 1870 was at the last hour diverted
against Khokand, which unexpectedly revolted.
Later on the Russian authorities exchanged their somewhat
menacing policy for one of peaceful penetration and attempted to
gain an entry into Chinese Turkestan through their merchants. They
also sent a young officer to discuss various questions with Yakub
Beg, who in turn despatched one of his nephews to Russia. As,
however, his envoy was accorded no official recognition, little
progress was made in developing relations, and the Atalik
maintained towards his formidable rival an uncompromising attitude,
which convinced the Russians that his power was much greater than
was actually the case.
Accordingly, in 1872, although military preparations were continued,
an accredited envoy, Baron Kaulbars, was entrusted with the difficult
task of opening up official relations with the Atalik. He was received
by the gratified ruler with the extravagant expression of Oriental
hyperbole: “Sit on my knees, on my bosom, or where you like, for
you are guests sent to me from heaven.” For the first time complete
freedom was accorded to the envoy, and two Russian merchants
who accompanied the mission were granted every facility for visiting
Yarkand and Khotan. Baron Kaulbars was so fully impressed with a
sense of the power of his host that he regarded him as a potentate
ranking with the Amir of Afghanistan; and, owing to these
impressions, a treaty of commerce, satisfactory to both parties, was
drawn up, Russian goods being subjected to a maximum charge of
2½ per cent ad valorem. The envoy, who had learnt a good deal
about the country and had certainly scored a great personal
success, returned to Tashkent with glowing accounts of the Atalik
and his dominions.
Another nephew of Yakub Beg’s, Haji Tora by name, who had
travelled widely, was next despatched to Russia, where he was
received with much honour and entertained by the Tsar. From the
court of the Northern Power he went on to visit Constantinople,
where he conducted negotiations by which Yakub Beg, in return for
an acknowledgment of his independence, accepted the suzerainty of
the Sultan and issued coins bearing his effigy. Furthermore, as a
mark of high favour, the Atalik was gazetted an Amir, with the title of
Amin-ul-Muminin or “The Trusted One of the Believers.”
The Russian authorities in Central Asia naturally took umbrage at an
alliance which united a leading Moslem power with their hereditary
foe. Moreover, relations with Yakub Beg were not developing
smoothly; for, realizing that his state would be overrun by Russian
merchants, the Amir decided to go back on the spirit of the treaty of
commerce and to discourage all Russian intruders. In the case of the
first important caravan to reach Kashgar, he kept the owners under
surveillance although he purchased their goods at a fair rate through
one of his agents. But, as the payment was made in debased
coinage the merchant stood to lose, and finally did lose, in spite of
strenuous official Russian support. A year later Yakub again changed
his mind and invited another Russian merchant to visit Kashgar. He
received better treatment, with the result that trade gradually
increased. The chief aim of Russia was to be permitted to appoint an
Agent at Kashgar, whereas Yakub Beg would only allow a
Caravanbashi or Superintendent of caravans (a man of little standing
or education) to reside at the capital. In 1874 a Russian official was
sent to arrange this question, but Yakub Beg, relying on the support
of Great Britain, was entirely unyielding on the subject; indeed, his
attitude towards Russia became almost menacing. So much was this
the case that in the autumn of the same year the Russian authorities
decided to break his power. They had massed twenty thousand
troops on the frontiers, when a revolt in Khokand forced General
Kaufmann to divert his forces. Had Yakub Beg been a great man he
would have seized the opportunity to aid Khokand, and would
thereby, in all probability, have given a serious set-back to the Power
which had resolved on his destruction. His inaction on this occasion
stamps him as an Oriental adventurer who kept the kingdom he had
won rather by good fortune than by signal capacity.
The relations of Yakub Beg with the Indian Empire were of little
permanent importance from the political point of view, but are of
considerable interest to the geographer and to the student of politics
and commerce. In the middle of the nineteenth century the British
representative in Ladak heard vague accounts of affairs in Chinese
Tartary, as it was then termed, from merchants, but gained little or no
accurate information, although the veil was lifted somewhat in 1857
by Adolph Schlagintweit, the first European to travel from India to
Yarkand and Kashgar. Unfortunately for him, Wali Khan was
besieging the Chinese cantonment of Kashgar at that time, and by
his orders the German explorer was murdered. Eight years later, in
1865, Johnson,[14] an English surveyor, crossed the Kuen Lun to
Khotan, where he was received with much hospitality by its chief; but
to Robert Shaw belongs the credit of being the first Englishman to
explore this unknown land and open up relations with its ruler and
people.
While he was living at Ladak an agent of Yakub Beg passed through,
bound for the Punjab, under orders from his master to report on the
neighbouring land. Shaw mentioned to this agent his intense desire
to visit Yarkand and Kashgar for the purpose of paying his respects
to its celebrated ruler. This proposal was almost immediately agreed
to, and late in 1868 Shaw crossed the Kara Koram and reached
Yarkand safely. His courage and resolution were evidently combined
with considerable tact, as throughout his journey he created an
excellent impression both on Yakub Beg and on his officials. The
inopportune arrival of another Englishman, Hayward, who was an
explorer and also a trader, aroused suspicions in the mind of the
Oriental, and both men were treated for a while as honoured state
prisoners; but in the end they were sent back to Ladak, thoroughly
pleased with their reception.
Shaw’s reports excited intense interest, and created exaggerated
ideas both as to the power of Yakub Beg and as to the richness of
the prospective market. He had suggested to the Atalik the
appointment of an agent for Chinese Turkestan at Lahore. This
suggestion was accepted, and the agent was the bearer of a cordial
invitation to the Government of India to despatch an official for the
purpose of establishing friendly relations and opening up trade.
Forsyth, a capable Indian civilian, was appointed to carry out this
mission, and, accompanied by Shaw, he reached Yarkand in 1870;
but unfortunately the Atalik had just started off to his distant eastern
frontier, and Forsyth returned to India without accomplishing his
object.
Yakub Beg was as much disappointed as the British envoy at this
fiasco, and through the insistence of his agent Forsyth was again
appointed in 1873 to head a mission, which was of greater size than
its predecessor. Under him were Lieut.-Colonel Gordon, Captain
Chapman and Captain Trotter, who have all had distinguished
careers. The caravan, consisting of 400 animals, required elaborate
supply preparations, and great difficulty was experienced in crossing
one of the passes, the last hundred feet of which was a wall of ice.
But in due course Kargalik was reached, and thenceforward the
mission was treated with friendliness and sumptuous hospitality. In
December 1873 the party reached Kashgar, and Forsyth describes
his reception as follows:
“According to etiquette we dismounted at about forty paces from the
gateway, and walked slowly along with the Head Chamberlain going
ahead. In the outer gateway soldiers were seated on a daïs with their
firearms laid on the ground before them, their arms folded and their
eyes on the ground. We then passed through a second gateway
filled with soldiers, and crossed another court, on all sides of which
soldiers in gay costumes were ranged seated. From this court we
passed into the penetralia, a small court in which not a soul was
visible, and everywhere a deathlike silence prevailed. At the further
end of this court was a long hall, with several window-doors. The
Chamberlain then led us in single file, with measured tread, to some
steps at the side of the hall, and entering almost on tiptoe looked in,
and returning, beckoned with his hand to me to advance alone. As I
approached the door he made a sign for me to enter, and
immediately withdrew. I found myself standing at the threshold of a
very common-looking room; looking about I saw enter at a doorway
on the opposite side a tall stout man, plainly dressed. He beckoned
with his hand, and I advanced, thinking it must be a chamberlain who
was to conduct me to ‘The Presence.’ Instinctively, however, I made
a bow as I advanced, and soon found myself taken by both hands
and saluted with the usual form of politeness, and I knew that I was
standing before the far-famed ruler of Eastern Turkestan.”
This interesting description shows that Forsyth took Yakub Beg very
much at his own valuation, and the fact that the British envoy agreed
to dismount at a distance from the gateway must, at any rate, have
raised the Atalik in the eyes of his subjects.
At the formal interview a few days later the gifts, consisting mainly of
munitions, were presented, but Yakub Beg was chiefly pleased with
the autograph letter from Her Majesty, which was enclosed in a
magnificent casket. After exclaiming “Praise to Allah!” several times
he proceeded to declare his friendship for the British, referring to the
Queen as the sun “in whose genial rays such poor people as I
flourish.”
The mission remained four months at Kashgar, its labours
culminating in a treaty of commerce which was concluded in
February 1874. By its terms a 2½ per cent ad valorem tax was to be
levied on goods imported from India, British trade thus being placed
on the same favourable footing as Russian.[15]
In addition to important surveys made along the main road, Gordon
led a party to the Pamirs, which were explored to some extent.
Indeed the Forsyth mission was a distinct success, if only because
these surveys proved beyond doubt that India could not be seriously
invaded from the Pamirs or from Chinese Turkestan. Moreover, it
enlarged the horizon of the authorities in India, and by the
establishment of friendly relations with Chinese Turkestan
inaugurated a small but profitable trade.
Yakub Beg, however, regarded the mission far otherwise, as to him it
signified an alliance, granting British protection against Russian
hostility, and, had he retained his power, constant appeals for aid
would have been received at Calcutta. As matters turned out, both
Yakub Beg and his family were destined to disappear from the stage
of Central Asia, and that speedily.
While the Atalik was entertaining the Forsyth mission the Chinese
Government, having restored order at home, was preparing a
formidable force for the reconquest of its lost possessions beyond
the Gobi. The task was very difficult, owing to the width of the desert,
estimated at about 1200 miles, but the Chinese army was well
disciplined, well equipped, and well led, the difficulty as to supplies
being successfully overcome in a very simple manner. The advanced
guard sowed crops in one of the rare oases, and an abundant
harvest was thus provided in the following autumn.
As soon as this was gathered in, an army 50,000 strong advanced
without encountering any serious opposition, until in the spring of
1876 it reached the neighbourhood of Urumchi. The capture of this
town in August, followed by that of Manas, fully re-established
Chinese authority to the north of the Tian Shan.
The Celestials were now free to deal with Yakub Beg, whose position
had become unenviable. His refusal to aid Khokand in her last
desperate struggle with Russia must have lowered his prestige,
while his hostility to that power must have weakened his position; it
was clear, too, that Great Britain had no intention of supporting him
with troops or money. Apart from this, his heterogeneous force was
no match for the veteran Chinese army, to which, moreover, it was
far inferior in numbers and equipment.
In the spring of 1877 the Chinese main force marched on Turfan,
crossing the Tian Shan by the Devanchi Pass; while a second force,
10,000 strong, moved west from Hami in co-operation. Yakub Beg
had placed his main body for the defence of the Devanchi Pass, but
while it was holding this position news was received of the capture of
Turfan by the Hami column. A panic ensued, and, although the Atalik
fought a rearguard action to the west of Turfan, he was obliged to
retreat to Karashahr, and later to Korla. Before this defeat Yakub Beg
had sought aid from Russia, but in vain, partly because Kuropatkin
(then a captain) had visited his camp and reported most
unfavourably on his position.
For some unexplained reason, probably from lack of supplies, the
Chinese army remained immobile for several months, while events
were moving fast in the enemy camp, where the star of Yakub Beg
was setting in gloom. After losing the eastern part of his territory the
Atalik became morose and a danger to his courtiers. According to
trustworthy information gained by me in Kashgar, the actual cause
that led up to his death was a savage flogging, inflicted without any
adequate reason, on one of his officials. This alarmed Niaz Hakim
Beg, one of his principal followers, who poisoned him.
Thus died Yakub Beg, who for a period of twelve years had played a
leading rôle on the stage of Central Asia. He was fortunate, as one of
his titles of Bedolat signified, inasmuch as he quitted Khokand just
before its fall and successfully founded a state only a few marches
off. He was fortunate in his dealings with Russia, which would have
crushed him, but for more serious tasks which stayed her hand, and
finally he was fortunate in being killed just as his kingdom was falling
from his grasp. Among the chiefs of Central Asia he was a man of
capacity, and he was undoubtedly brave and resolute; but his
outlook was narrow, as was inevitable from his environment. He
remained alert and virile to the end, and was not addicted to the vice
or self-indulgence that ruins many members of the upper classes in
Central Asia. Although the stage he trod was circumscribed, Yakub
Beg is the only Moslem of the nineteenth century in Central Asia
whose name will live.
The death of the Atalik was followed by a period of confusion. One of
his sons escorted his father’s corpse to Kashgar. There he was
murdered by his elder brother Beg Kuli Beg, who succeeded to the
throne, but not unchallenged, as a certain Hakim Khan Torah was
able to seize Karashahr and Korla, and there were also outbreaks at
Khotan. The new ruler in the end overcame his rivals, but in the
effort exhausted his resources to a dangerous extent and made the
way still easier for the Chinese.
The final operations for the recovery of Kashgar and Yarkand were
conducted on somewhat the same lines as the first. The main force
assembled to the north of the Tian Shan and, using a little-known
pass, descended in overwhelming strength on Aksu, while a second
column drove the Moslems before it to Karashahr and on to Kucha,
where a hard-fought battle was won by the Chinese; and in
December 1877 the campaign was brought to a successful
conclusion by the capture of Kashgar.
The Celestials showed moderation in the hour of victory. They
deprived the population of their horses, to prevent a fresh rising, but
they appointed Moslem headmen and also recognized the religious
law of Islam. Their strong position was acknowledged by Russia in
1881, when, by the Treaty of St. Petersburg, that Power restored
Kulja to the Chinese, receiving in return the post of Irkeshtam, two
stages on the eastern side of the Tian Shan. By the same treaty
freedom of trade was secured, and this agreement is still in force.
In the last two decades of the nineteenth century great forward
strides were made in the direction of Chinese Turkestan both by
Great Britain and by Russia. The former Power, thanks to the energy
and activity of Younghusband (a nephew of Robert Shaw) and other
travellers, realized the importance of exploring the passes through
which India could be threatened, if not invaded, from Russian
Turkestan. A second aim was the control of the No Man’s Land
which lay between the fertile valley of Kashmir and the plain of
Chinese Turkestan. To this end British Political officers were
stationed at Gilgit and Chitral, supported by the Imperial Service
troops of the Maharaja of Kashmir.
During this period Russia also displayed considerable activity in the
exploration and occupation of the No Man’s Land bordering on
Russian Turkestan. One of her most active agents, Captain
Grombchevsky, visited the hill state of Hunza in 1888, meeting
Younghusband in the following year on the upper reaches of the
Yarkand River. In 1891 Younghusband travelled in Wakhan, and at
the stage of Bozai Gumbaz met Colonel Yonoff, who had issued a
proclamation that the Pamirs (with the sole exception of the
Taghdumbash Pamir) were Russian territory. That officer
subsequently received instructions to escort Younghusband back to
Chinese territory. He showed good feeling about his disagreeable
task, and as Younghusband agreed, under protest, to proceed to
Chinese Turkestan, he waived the instructions relating to escort.
Upon this incident being reported, the Russian Government
apologized for Yonoff’s act, and the two Powers finally decided to
despatch a commission to settle their respective claims in a country
visited hitherto merely by a few travellers. In 1895 the commission
met, and by its findings the narrow strip of Wakhan was awarded to
the Amir of Afghanistan, with the result that the boundary of the
British Empire was drawn in this section some thirty miles to the
north of the crest line of the Hindu Kush.
The great revolution which had broken out in China in 1911 began to
make itself felt in its remote western provinces in the following
spring. The first outbreak occurred in the district of Ili, where a young
officer entered into a conspiracy against the Tartar general, with
whom he had a private quarrel. The conspiracy was entirely
successful, and resulted not only in the murder of the general, but in
the capture of the machinery of government. As the revolution
progressed in China, the republic was proclaimed in Ili, and after the
defeat of a force despatched from Urumchi the Ili rebels became
undisputed rulers of the surrounding country.
The unrest soon affected Urumchi itself, where Chinese rowdies,
members of a secret society which existed for the sake of loot and
blackmail, began to demonstrate in favour of the republican cause
and to show their sympathy by acts of robbery and incendiarism. The
governor, however, was no weakling, and realizing that the loyalty of
the regular troops was very doubtful, he enlisted Tunganis in
considerable numbers, through whose instrumentality he was able to
control the situation for a time. Subsequently he dealt so mercilessly
with every one suspected of being a member of the secret society,
slowly slicing to death innocent and guilty alike, that the Chinese
population rose and drove him out of Urumchi.
In April of this year the outward calm hitherto maintained in Kashgar
was rudely disturbed by the murder of the Taotai and the Prefect of
Aksu. Upon the arrival of the telegram announcing this deed, the
Kashgar Taotai immediately cut off his queue and issued a
proclamation advising the Chinese to follow his example. Moreover,
he had a scroll prepared with the inscription, “Long live the Chinese
Republic!” which he hung up in his yamen. After some hesitation the
leading Chinese officials followed the example of the governor, the
commander-in-chief of the province not only cutting off his queue
and flying the flag of the Republic, but donning a nondescript
European cap. The united officials then solemnly changed their
chronological system from the fourth year of Hsuang-tang, the boy-
emperor, to the first year of the Chinese Republic, an act which
possessed tremendous significance in their eyes. The soldiers were
by no means ready to follow the lead of their superior officers, but
maintained a sullen and resentful attitude, which boded ill for the
safety of the higher officials, military and civil alike.
Meanwhile Yuan-Shih-Kai had been informed by telegram of the
adherence of the New Dominion to the Republic and had appointed
the governor of Kashgar to Urumchi, hoping by this means to end
the state of hostility which still existed between Ili and Urumchi. The
governor of Kashgar at first refused the appointment, pleading his
age and weak health, but in the end accepted it. The actual position,
therefore, was that the Republic had been acknowledged throughout
the province, and that the Chinese officials were all obeying the
instructions of Yuan-Shih-Kai. It might have been supposed that the
crisis had passed without bloodshed, but this was not so. At night a
band of fifty Chinese, members of a secret society, forced their way
into the yamens of the governor and of the city magistrate. The
governor, who was awake, was greeted with the ironical
exclamation,“Greetings to Your Excellency,” and both he and his wife
were cut to pieces. The magistrate was also killed and the republican
flags in the two yamens were cut down and destroyed.
In the morning the gamblers, as they were termed, were harangued
by the commander of the garrison at the head of a few soldiers. They
insisted on being armed and formed into a new regiment under the
command of a ruffian, a pork-butcher by trade; and when this was
done they appointed new officials to succeed the murdered men.
The soldiers in the New City killed two of their officers and a panic
ensued in Kashgar, but the disturbances and looting were confined
to the New City. The administration was now controlled by the gang
of gamblers, who appointed all officials and took advantage of their
power to levy blackmail, mainly on Chinese officials. In the other
centres there were murders. The governor of Yarkand, among
others, was singled out for assassination; but an exceptionally
violent storm, which turned day into night, suggested to the Chinese
gamblers that heaven forbade the deed—and the official still lives to
tell the tale.
In consequence of the unrest and lack of security caused by these
deeds of violence, the Russian Government despatched a force 800
strong to protect Russian subjects. For some weeks after its arrival
there was no friction or cause of alarm, but the celebration of a
Chinese rite nearly gave rise to most serious consequences. On the
day of the Festival of the Departed Spirits it is the custom of the
Chinese to burn paper-money before the temples in order to ensure
financial ease for their deceased relatives. One of the temples in
Kashgar was the scene of this ceremonial, and a rumour reached
the Russian consulate that the bazar was on fire. Help was
immediately despatched in the shape of fifteen Cossacks, who,
misunderstanding the situation, forcibly put out the fires in which the
paper-money was being burnt. While this was being done some of
the Cossack horses broke loose and galloped back to the consulate,
where considerable anxiety was felt. The city gate was shut at the
usual hour of 8 p.m., and, upon its arrival, the Russian main body,
under the impression that their detachment had been cut off, blew it
up with dynamite, and marching through the opening found the
Cossacks perfectly safe.
Not long after this the “Gambler” regiment was ordered to Urumchi,
and the officer commanding the Cossacks, who was disappointed at
the entirely peaceful attitude of the Chinese, decided to attack it, his
plan being to carry out night manœuvres to the east of the city
across the line of march—and to create a “regrettable incident.” But
he reckoned without Sir George Macartney, who, getting wind of this
typically Russian scheme, which received confirmation from the
sudden departure of the Cossacks, induced the Chinese authorities
at the very last minute to change the line of march from due east to
north-west, with a wide detour afterwards to the north. Thanks to this
action by our able representative the trap was set in vain. The
regiment, which had obeyed its orders with deep reluctance, finally
reached Urumchi with its numbers much diminished by desertion,
and the ruffianly pork-butcher was subsequently put to death. The
Russian troops were shortly afterwards withdrawn from Kashgar, and
that city once again settled down to its habitual drowsiness.
In conclusion, the old-world policy of China was to surround her
fertile empire with buffer states. At the end of the eighteenth century
these included Annam, Siam, Burma, Assam, Bhutan, Sikkim, Nepal,
Ladak, Kashmir and Khokand, together with the maritime provinces
of Siberia. But the nineteenth century, which saw the advance of
Russia, the rise of Japan, and also powerful strangers from the west
thundering at the watergates of the Middle Kingdom, brought heavy
territorial losses to China, and to-day her system of buffer states has
been swept away by the new powers. Great Britain has shown
considerable activity and has occupied or gained political
ascendency over many of these states, and at the present time
marches with the Chinese Empire not only on the confines of Burma
to the south, but also on the borders of Ladak and Kashmir.
Russia, on her side, has made a great advance, and now occupies
Khokand, Andijan and the Khanates generally, together with the
Pamirs to the west of Chinese Turkestan; to the north the Russian
province of Semirechia, through which is being constructed a railway
that will attract much of its commerce, overshadows the province of
Chinese Turkestan.
Thus the old order of isolation, on which China relied, is passing, and
the new order, which includes modern methods of communication, is
coming into force, hastened by the desire for progress which is
affecting large sections of mankind in Asia.
The future of Chinese Turkestan is not finally settled, but the World
War which has temporarily broken up the Russian Empire will
undoubtedly stimulate China to move along the path of progress. If
so, there is hope that the condition of this outlying province of her
empire may benefit, more especially by improved communications.
At the same time there are many parts of Asia which have reason to
envy the peace and plenty enjoyed by the inhabitants of Chinese
Turkestan.
CHAPTER XVI
A KASHGAR FARMER
La latitude assez basse du Turkestan chinois combinée avec son altitude
considérable, la sécheresse de son atmosphère et ses saisons nettement
tranchées rendent le pays propre à des cultures très diverses, à celles qui
se contentent d’un climat tempéré comme à celles qui exigent des
chaleurs fortes et prolongées; mais excluent les plantes qui craignent les
froids hivernaux ou réclament une grande humidité.—Grenard, La Haute
Asie, ii. 173.
The cultivator, who is the backbone of Chinese Turkestan, depends

entirely on irrigated crops, as there is no regular rainfall in the
country. Rain, termed the “mercy of Allah” in Persia, is considered to
be the opposite in Kashgar, partly because of the utter irregularity of
its incidence. If there be a heavy fall in the spring, the soil cakes and
the young plants cannot force their way through, and this
necessitates a fresh sowing. Rain at harvest time, or when the
melons ripen, is equally unwelcome, and when there is a heavy
rainfall the farmer exclaims, “What great crime has been committed
that we suffer such a calamity?” Snow is regarded with less
disfavour. As a rule there is plenty of water for every one in the
Kashgar oasis, and fights for it occur only in the spring, when each
cultivator wishes to water his land first, in order to secure an early
crop for the market.
Owing to the abundance of water and the absence of hail-storms or
other serious climatic drawbacks, agriculture, except for rust and
blight, which are seldom experienced, is a certainty, in complete
contrast to the reputation it bears in countries that depend on the
rainfall for their crops. The life of the oasis, where every acre is
cultivated and where the agricultural population is comparatively
dense, is quite unlike that of Persia, where each village is
surrounded by square miles of uncultivated land, which furnishes
grazing, fodder and fuel. There are a few isolated villages, or groups
of villages, in Chinese Turkestan, but the country generally consists
of extensive oases set in a lifeless desert.
The chief crops are millet, rice, maize, wheat, barley, cotton, lucerne
clover, hemp, linseed, turnips, carrots and tobacco. Millet and rice
are regarded as the best-paying crops, the former occupying one-
half of the total area cultivated.
Of fruits and vegetables, apricots, grapes, peaches, nectarines,
quinces, cherries, figs, apples, pears, mulberries, pomegranates and
melons grow in great profusion, and pumpkins, which are the staple
vegetable, are supplemented by carrots, turnips, onions, cucumbers,
garlic and fennel.
The upper classes are less civilized than in Persia, partly because
they do not mix socially with the European colonies; good fruit trees
and seeds have therefore not been introduced. This state of affairs
reflects little credit on the merchants from Andijan, who could easily
introduce the magnificent fruit trees which are now grown at
Tashkent.
The Chinese of the New City farm much better than the native
Moslems, and have introduced the curious plum-cherry, with its blue,
white and red varieties of fruit, beans of various kinds, beetroot,
cabbages, including kohl rabi, lettuces, potatoes, tomatoes and
spinach; but there is little contact between the Chinese and Moslem
farmers, so that the latter do not learn much from the efficient
Celestials.
The trees in the Kashgar Oasis, other than fruit trees, include the
Lombardy and the spreading poplar, the latter growing to a great
size, and the Turkestan elm, of which a grafted species grows in a
pyramidal shape. The common willow and the Babylonian willow of
two species—one with an edible fruit resembling the Bohemian olive
—are planted along every irrigation channel and serve as fuel.
Next to agriculture the most important industry is the raising of live-
stock—horses, donkeys, camels, cattle, sheep and goats. The
horses bred by the Kalmucks around Karashahr are the best, being
stronger than the Kirghiz ponies, because the Kalmucks do not drink
mare’s milk. They are usually geldings, standing about fourteen
hands, and are ideal for transport purposes. The Kirghiz pony is
hardy and enduring, but not strong or up to much weight. The
Yarkandi, especially a roan, was a favourite mount in India in the last
century, and is mentioned in Anglo-Indian novels of the period; it is
still exported in small numbers.
A LOAD OF CLOVER FROM ISA HAJI’S FARM.

Page 302.
Donkeys are found in thousands and take the place of the
wheelbarrow and the cart in England, besides carrying the bulk of
the internal trade. Camels, of the two-humped or Bactrian species,
are highly esteemed, especially by the Kirghiz, as they are not
affected by cold or deep snow, and can cross rivers that ponies have
to swim. Cattle-breeding is carried on mainly in the mountains and in
the wooded tracts along the courses of the rivers. The animals are
small, and are bred for milk and for ploughing. Sheep are usually of
the fat-tailed species, but in the southern districts there is also a
short-haired breed. All animals, as a rule, are miserably thin owing to
the almost entire absence of grazing.
I think it may be useful to select a typical farmer and study his life
closely; for by this means we shall get down to the bed-rock of
definite fact, which is preferable to vague generalizations about
agriculture. Isa Haji, the subject of this sketch, was a farmer, aged
75, who lived not far from the city wall. Helped by two of his five
sons, aged 18 and 16 respectively, he farmed 40 mows, or about six
acres of land, which is the average size of a farm close to Kashgar.
Here the manure obtained from the city enables the whole of the
land to be cultivated at once, whereas farther off, where little manure
is available, the farms are larger because a part of the land must
always be allowed to lie fallow. One half of the Haji’s land was
devoted to lucerne clover, the remainder being sown with millet,
wheat, rice, cotton, melons and linseed. As a rule only one crop a
year was taken off the land; but millet, carrots and turnips were sown
after the wheat crop; in this case the millet did not ripen, but was
valuable as green forage; the clover was cut four times in the year. In
one corner of the farm were willow trees, which were pollarded every
four years to serve as fuel for the owners. Isa Haji, being an old man,
merely assisted in watering the fields, while his sons did all the
ploughing, harvesting and threshing. His two eldest sons kept a
grain-shop in Russian Turkestan, the third was a bricklayer, and the
others, when not at work on the farm, earned sixpence a day as
labourers. The Haji owned a yoke of plough-oxen and four donkeys,
the former being fed on cotton-seed and the latter on millet. His
agricultural implements included a primitive plough, a harrow,
mattocks of two sizes, sickles, zambils or hurdles for carrying earth,

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Biochemistry 7th Edition Reginald H.

BioChemistry By Reginald H Garrett Charles M Grisham

Lippincott Illustrated Reviews Biochemistry 7th Edition

Lippincott Illustrated Reviews Biochemistry 7th Edition

Biochemistry of Lipids, Lipoproteins and Membranes 7th

Textbook of Biochemistry for Medical Students 7th

Atlas of Human Anatomy 7th Edition Frank H. Netter

QuickBooks Online For Dummies, 7th Edition David H.

Organic and Biological Chemistry 7th Edition H. Stephen

Reginald H. Garrett | Charles M. Grisham

With molecular graphic images

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To our grandchildren Jackson, Bella, Reggie, Ricky, Charlotte

Reginald H. Garrett and Charles M. Grisham

Part I Molecular Components of Cells 1

Part II Protein Dynamics 433

Part III Metabolism and Its Regulation 573

Part IV Information Transfer 981

Abbreviated Answers to Problems A-1

 itration Curves Illustrate the Progressive

5 in the Laboratory? 131

8 9.1 What Are the Chemical and Physical

 eripheral Membrane Proteins Associate Loosely

 ext-Generation Sequencing by Synthesis 348

14 15.1 What Factors Influence Enzymatic Activity? 511

 lagellar Filaments Are Composed of Protofilaments of

Metabolism: An Overview 573 Foundational Biochemistry 597

 tilization of Glucose-6-P Depends on the Cell’s Need

26.2 How Do Cells Synthesize Purines? 922 Foundational Biochemistry 945

 ukaryotic Cells Also Contain a Number of Different DNA

 he Regulation of Gene Expression Is More Complex in

 eptide Chain Elongation Requires Two G-Protein Family

31  teroid Hormones Act in the Nucleus or at the

Processing, and Degradation 1131 32.2 What Is Signal Transduction? 1164

Recombinant DNA Techniques Fluxomics Section 17.5

Objectives and Building on Previous Editions

New to the Online Course and Resources

New to this Edition

Chapter 27 New molecular graphic of mTORC1, the master integrator of information

●● Critical Developments in Biochemistry essays emphasize recent and historical advances

Instructor and Student Resources

Reviewers for the 7th edition

Reginald H. Garrett Charles M. Grisham

Phenomena “…everything that living things do can be

 A sperm fertilizing an egg.

Essential Question Key Questions

Science Photo Library/Alamy

degree of organization in their intricate three-dimensional architecture, even though

Figure 1.2 ​ATP and NADPH, two biochemically important O

Living systems have a remarkable capacity for self-replication. Generation after

Figure 1.3 ​Organisms resemble their parents. Orangutan with infant.

were significantly greater, the evolution of organisms would be hampered. This is so

itration Curves Illustrate the Progressive

eripheral Membrane Proteins Associate Loosely

ext-Generation Sequencing by Synthesis 348

lagellar Filaments Are Composed of Protofilaments of

tilization of Glucose-6-P Depends on the Cell’s Need

ukaryotic Cells Also Contain a Number of Different DNA

he Regulation of Gene Expression Is More Complex in

eptide Chain Elongation Requires Two G-Protein Family

31 teroid Hormones Act in the Nucleus or at the

Figure 1.2 ATP and NADPH, two biochemically important O

Figure 1.3 Organisms resemble their parents. Orangutan with infant.

Figure 1.5 Covalent bond formation by e2 pair