Biochemistry: concepts and connections

934 Pages·2019·199.18 MB·English

by  Anthony-Cahill, Spencer J., Appling, Dean Ramsay, Mathews, Christopher K

BIOCHEMISTRY
Concepts & M A A
a n p
th th pl
Connections ew ony ing
s -
C
a
SECOND EDITION h
i
l
l
B
Appling You probably have heard that humans
and our closest living rela- I
Anthony-Cahill O
tives, chimpanzees, share
C
Mathews 99% of our DNA sequences.
H
How could the resulting
1% difference account for the E
incredible physical and behavioral M
differences between our two species?
I
Interestingly, the same mechanism
S
that contributes to the tremendous diver-
T
sity of antibodies available to combat foreign
R
antigens in human cells—alternative splicing of
Y
gene transcripts—may also help explain some of the variation we observe
between species. Evidence suggests that 6–8% of related expressed
BIOCHEMISTRY
sequences demonstrate significant splicing differences between our two S CC Concepts &
E
C oo
species. The human spliceosome pictured on the front cover (supplied ON nn
D nc
E ee Connections
by Dr. Berthold Kastner and colleagues) appears to play a major role in DIT cp
IO tits
the generation of genetic variation within our cells as well as potentially N o
n&
SECOND EDITION
s
explaining some of the diversity of life more generally.
Appling
Anthony-Cahill
Please visit us at www.pearson.com for more information.
To order any of our products, contact our customer service Mathews
department at [phone], or [phone] outside of
the U.S., or visit your campus bookstore.
www.pearson.com
ISBN-13: 978-0-13-464162-1
ISBN-10: 0-13-464162-0
9 0 0 0 0
9 780134 641621
APPL1621_02_cvrmech.indd 1 10/11/17 4:10 PM
Biochemistry
C O N C E P T S A N D C O N N E C T I O N S
SECOND EDITION
Dean R. Appling
THE UNIVERSITY OF TEXAS AT AUSTIN
Spencer J. Anthony-Cahill
WESTERN WASHINGTON UNIVERSITY
Christopher K. Mathews
OREGON STATE UNIVERSITY
330 Hudson Street, New York, NY 10013
A01_APPL1621_02_SE_FM.indd 1 08/11/17 1:01 PM
Editor in Chief: Jeanne Zalesky Illustrators: ImagineeringArt, Inc.
Acquisitions Editor: Chris Hess Photo Researcher: Mo Spuhler
Director of Development: Jennifer Hart Photo Lead: Maya Melenchuk / Eric Shrader
Marketing Manager: Elizabeth Bell Photo Permissions: Kathleen Zander / Matt Perry
Development Editor: Matt Walker Operations Specialist: Stacey Weinberger
Art Development Editor: Jay McElroy Cover Background Photo Credit: The Human
Program Manager: Kristen Flathman Spliceosome
Content Producer: Anastasia Slesareva Dr. Berthold Kastner, Max Planck lnstitute of
Text Permissions Project Manager: Tim Nicholls Biophysical Chemisty
Text Permissions Specialist: James Fortney, Molecular graphics and analyses were performed
Lumina Datamatics with the UCSF Chimera package. Chimera is
Project Management Team Lead: David Zielonka developed by the Resource for Biocomputing,
Production Management: Mary Tindle, Cenveo Visualization, and Informatics at the University of
Compositor: Cenveo California, San Francisco (supported by NIGMS
Design Manager: Marilyn Perry P41-GM103311)
Interior Designer: Elise Lansdon Chimpanzee Photo Credit: Fiona Rogers/Getty
Cover Designer: Mark Ong, Side by Side Studios Images
Copyright © 2019, 2016 Pearson Education, Inc. All Rights Reserved. Printed in the United States of America.
This publication is protected by copyright, and permission should be obtained from the publisher prior to any
prohibited reproduction, storage in a retrieval system, or transmission in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise. For information regarding permissions, request forms, and
the appropriate contacts within the Pearson Education Global Rights & Permissions Department, please visit
www.pearsoned.com/permissions.
Acknowledgments of third-party content appear on pages C-1–C-3, which constitutes an extension of this
copyright page.
PEARSON, ALWAYS LEARNING, MasteringTM Chemistry, and Learning Catalytics are exclusive trademarks
in the U.S. and/or other countries owned by Pearson Education, Inc. or its affiliates.
Unless otherwise indicated herein, any third-party trademarks that may appear in this work are the property
of their respective owners, and any references to third-party trademarks, logos, or other trade dress are for
demonstrative or descriptive purposes only. Such references are not intended to imply any sponsorship,
endorsement, authorization, or promotion of Pearson’s products by the owners of such marks, or any relationship
between the owner and Pearson Education, Inc. or its affiliates, authors, licensees, or distributors.
Library of Congress Cataloging-in-Publication Data
Names: Appling, Dean Ramsay, author. | Anthony-Cahill, Spencer J., author. |
Mathews, Christopher K., 1937- author.
Title: Biochemistry : concepts and connections / Dean R. Appling, Spencer J.
Anthony-Cahill, Christopher K. Mathews.
Description: Second edition. | New York : Pearson, [2019] | Includes
bibliographical references and index.
Identifiers: LCCN 2017047599| ISBN 9780134641621 | ISBN 0134641620
Subjects: | MESH: Biochemical Phenomena
Classification: LCC RB112.5 | NLM QU 34 | DDC 612/.015--dc23
LC record available at https://lccn.loc.gov/2017047599
[Third-Party Trademark] [TM/®] is a [registered] trademark of [Third Party]. Used under license.
1 18
ISBN 10: 0-134-64162-0; ISBN 13: 978-0-134-64162-1
www.pearson.com
A01_APPL1621_02_SE_FM.indd 2 10/11/17 10:30 AM
Brief Contents
1 16
Biochemistry and the Language Lipid Metabolism 512
of Chemistry 2
17
Interorgan and Intracellular Coordination of
2
The Chemical Foundation of Life: Weak Energy Metabolism in Vertebrates 556
Interactions in an Aqueous Environment 18
18
Amino Acid and Nitrogen Metabolism 576
3
The Energetics of Life 48
19
Nucleotide Metabolism 610
4
Nucleic Acids 72
20
Mechanisms of Signal Transduction 636
5
Introduction to Proteins: The Primary Level
21
Genes, Genomes, and Chromosomes 664
of Protein Structure 108
22
6 DNA Replication 686
The Three-Dimensional Structure of
Proteins 144 23
DNA Repair, Recombination,
7 and Rearrangement 714
Protein Function and Evolution 190
24
8 Transcription and Posttranscriptional
Enzymes: Biological Catalysts 232
Processing 742
9
Carbohydrates: Sugars, Saccharides,
25
Information Decoding: Translation and
Glycans 278
Posttranslational Protein Processing 766
10
Lipids, Membranes, and Cellular
26
Regulation of Gene Expression 796
Transport 304
11
Chemical Logic of Metabolism 340
APPENDIX I: ANSWERS TO SELECTED
12 PROBLEMS A-1
Carbohydrate Metabolism: Glycolysis,
Gluconeogenesis, Glycogen Metabolism, APPENDIX II: REFERENCES A-20
and the Pentose Phosphate Pathway 374
CREDITS C-1
13
The Citric Acid Cycle 420
INDEX I-1
14
Electron Transport, Oxidative
Phosphorylation, and Oxygen
Metabolism 450
15
Photosynthesis 486
iii
A01_APPL1621_02_SE_FM.indd 3 10/11/17 10:30 AM
Contents
1
Water as a Solvent 27
CHAPTER
Ionic Compounds in Aqueous Solution 28
Biochemistry and
Hydrophilic Molecules in Aqueous Solution 28
the Language
Hydrophobic Molecules in Aqueous Solution 28
of Chemistry 2
Amphipathic Molecules in Aqueous Solution 29
2.4 Acid–Base Equilibria 29
1.1 The Science of
Biochemistry 4 Acids and Bases: Proton Donors and Acceptors 30
Ionization of Water and the Ion Product 30
The Origins of Biochemistry 4
The pH Scale and the Physiological pH Range 31
The Tools of Biochemistry 6
Weak Acid and Base Equilibria: K and pK 32
Biochemistry as a Discipline a a
and an Interdisciplinary Science 6 Titration of Weak Acids: The Henderson–Hasselbalch
Equation 33
1.2 The Elements and Molecules of Living Systems 7
Buffer Solutions 34
The Chemical Elements of Cells and Organisms 7
Molecules with Multiple Ionizing Groups 35
The Origin of Biomolecules and Cells 8
2.5 Interactions Between Macroions in Solution 38
The Complexity and Size of Biological Molecules 8
Solubility of Macroions and pH 38
The Biopolymers: Proteins, Nucleic Acids,
and Carbohydrates 9 The Influence of Small Ions: Ionic Strength 40
Lipids and Membranes 11 TOOLS OF BIOCHEMISTRY 2A Electrophoresis and
Isoelectric Focusing 44
1.3 Distinguishing Characteristics of Living Systems 11
FOUNDATION FIGURE Biomolecules:
1.4 The Unit of Biological Organization: The Cell 13
Structure and Function 46
1.5 Biochemistry and the Information Explosion 14
3
2
CHAPTER
CHAPTER
The Energetics of Life 48
The Chemical Foundation
of Life: Weak Interactions
3.1 Free Energy 50
in an Aqueous
Thermodynamic Systems 50
Environment 18
The First Law of Thermodynamics
and Enthalpy 50
2.1 The Importance of
The Driving Force for a Process 51
Noncovalent Interactions
Entropy 52
in Biochemistry 20
The Second Law of Thermodynamics 53
2.2 The Nature of Noncovalent Interactions 21
3.2 Free Energy: The Second Law in Open Systems 53
Charge–Charge Interactions 22
Free Energy Defined in Terms of Enthalpy and Entropy
Dipole and Induced Dipole Interactions 23
Changes in the System 53
Van der Waals Interactions 23
An Example of the Interplay of Enthalpy and Entropy:
Hydrogen Bonds 24
The Transition Between Liquid Water and Ice 54
2.3 The Role of Water in Biological Processes 26 The Interplay of Enthalpy and Entropy: A Summary 54
The Structure and Properties of Water 26 Free Energy and Useful Work 56
iv
A01_APPL1621_02_SE_FM.indd 4 08/11/17 1:02 PM
Contents | v
3.3 The Relationships Between Free Energy, Alternative Nucleic Acid Structures: B and A Helices 84
the Equilibrium State, and Nonequilibrium DNA and RNA Molecules in Vivo 86
Concentrations of Reactants and Products 56 DNA Molecules 86
Equilibrium, Le Chatelier’s Principle, and the Circular DNA and Supercoiling 87
Standard State 56
Single-Stranded Polynucleotides 88
Changes in Concentration and ΔG 57
4.4 Alternative Secondary Structures of DNA 90
ΔG versus ΔG°, Q versus K, and Homeostasis
Left-Handed DNA (Z-DNA) 90
versus Equilibrium 57
Water, H+ in Buffered Solutions, and the “Biochemical Hairpins and Cruciforms 91
Triple Helices 91
Standard State” 59
G-Quadruplexes 92
3.4 Free Energy in Biological Systems 60
4.5 The Helix-to-Random Coil Transition:
Organic Phosphate Compounds
Nucleic Acid Denaturation 93
as Energy Transducers 60
Phosphoryl Group Transfer Potential 63 4.6 The Biological Functions of Nucleic Acids:
Free Energy and Concentration Gradients: A Close Look at A Preview of Genetic Biochemistry 94
Diffusion Through a Membrane 63 Genetic Information Storage: The Genome 94
ΔG and Oxidation/Reduction Reactions in Cells 64 Replication: DNA to DNA 94
Quantification of Reducing Power: Standard Reduction Transcription: DNA to RNA 95
Potential 64
Translation: RNA to Protein 95
Standard Free Energy Changes in Oxidation–Reduction
TOOLS OF BIOCHEMISTRY 4A Manipulating DNA 99
Reactions 66
Calculating Free Energy Changes for Biological Oxidations TOOLS OF BIOCHEMISTRY 4B An Introduction
under Nonequilibrium Conditions 67 to X-Ray Diffraction 104
A Brief Overview of Free Energy Changes in Cells 67
5
CHAPTER
4
Polymerized sickle hemoglobin
CHAPTER Introduction to Proteins:
Nucleic Acids 72 The Primary Level of
Protein Structure 108
4.1 Nucleic Acids—
Informational 5.1 Amino Acids 111
Macromolecules 74 Structure of the α-Amino
The Two Types of Nucleic Acid: Acids 111
Zoom of contact surface
DNA and RNA 74 Stereochemistry of the α-Amino Acids 111
Properties of the Nucleotides 76 Properties of Amino Acid Side Chains:
Stability and Formation of the Classes of α-Amino Acids 115
Phosphodiester Linkage 77 Amino Acids with Nonpolar Aliphatic Side Chains 115
Amino Acids with Nonpolar Aromatic Side Chains 115
4.2 Primary Structure of Nucleic Acids 79
Amino Acids with Polar Side Chains 116
The Nature and Significance of Primary Structure 79
Amino Acids with Positively Charged (Basic) Side Chains 116
DNA as the Genetic Substance: Early Evidence 80
Amino Acids with Negatively Charged (Acidic) Side Chains 117
4.3 Secondary and Tertiary Structures
Rare Genetically EncodedS Aicmklein o Acids 117 Normal
of Nucleic Acids 81
Modified Amino Acids 1h1e7moglobin hemoglobin
The DNA Double Helix 81 (valine mutation) (glutamic acid)
5.2 Peptides and the Peptide Bond 117
Data Leading Toward the Watson–Crick
Double-Helix Model 81 The Structure of the Peptide Bond 118
X-Ray Analysis of DNA Fibers 81 Stability and Formation of the Peptide Bond 119
Semiconservative Nature of DNA Replication 83 Peptides 119
Polypeptides as Polyampholytes 120
A01_APPL1621_02_SE_FM.indd 5 17/11/17 3:50 PM
vi | Contents
5.3 Proteins: Polypeptides of Defined Sequence 121 Disulfide Bonds and Protein Stability 164
Prosthetic Groups, Ion-Binding,
5.4 From Gene to Protein 123
and Protein Stability 165
The Genetic Code 123
Posttranslational Processing of Proteins 124 6.5 Dynamics of Globular Protein Structure 166
Kinetics of Protein Folding 166
5.5 From Gene Sequence to Protein Function 125
The “Energy Landscape” Model of Protein Folding 167
5.6 Protein Sequence Homology 127
Intermediate and Off-Pathway States
TOOLS OF BIOCHEMISTRY 5A Protein Expression in Protein Folding 168
and Purification 131 Chaperones Faciliate Protein Folding in Vivo 168
Protein Misfolding and Disease 170
TOOLS OF BIOCHEMISTRY 5B Mass, Sequence,
and Amino Acid Analyses of Purified Proteins 138
6.6 Prediction of Protein Secondary and Tertiary
Structure 171
6 Folded protein Prediction of Secondary Structure 171
CHAPTER Tertiary Structure Prediction: Computer Simulation
The Three-Dimensional of Folding 172
Structure of Proteins 144
6.7 Quaternary Structure of Proteins 172
Symmetry in Multisubunit Proteins: Homotypic
6.1 Secondary Structure:
Protein–Protein Interactions 172
Regular Ways to Fold the
Heterotypic Protein–Protein Interactions 174
Polypeptide Chain 146
Local unfolding of
TOOLS OF BIOCHEMISTRY 6A Spectroscopic
Theoretical Descriptions of destabilized region
Methods for Studying Macromolecular Conformation
Regular Polypeptide Structures 146
in Solution 178
α Helices and β Sheets 148
TOOLS OF BIOCHEMISTRY 6B Determining
Describing the Structures: Helices and Sheets 148
Molecular Masses and the Number of Subunits
Amphipathic Helices and Sheets 149
in a Protein Molecule 185
Ramachandran Plots 150
FOUNDATION FIGURE Protein Structure
6.2 Fibrous Proteins: Structural Materials
and Function 188
of Cells and Tissues 152
The Keratins 152
7
Fibroin 153
CHAPTER
Collagen 154
Protein Function
6.3 Globular Proteins: Tertiary Structure
and Evolution 190
and Functional Diversity 156
Different Folding for Different Functions 156 7.1 Binding a Specific Target:
Different Modes of Display Aid Our Understanding Antibody Structure and
of Protein Structure 156 Function 192
Association of unfolded
Varieties of Globular Protein Structure: regions to form amyloid fibril
7.2 The Adaptive Immune Response 192
Patterns of Main-Chain Folding 157
Formation of
7.3 The Structure of Antibodies 193 amyloid deposits
6.4 Factors Determining Secondary
and Tertiary Structure 161 7.4 Antibody:Antigen Interactions 195
A B
The Information for Protein Folding 161 Shape and Charge Complementarity 196
The Thermodynamics of Folding 162 Generation of Antibody Diversity 197
Whole-body scan of a patient with amyloidosis (dark areas) at diagnosis (A), after treatment (B).
Conformational Entropy 162
7.5 The Immunoglobulin Superfamily 198
Charge–Charge Interactions 163
7.6 The Challenge of Developing an AIDS Vaccine 198
Internal Hydrogen Bonds 163
Van der Waals Interactions 163 7.7 Antibodies and Immunoconjugates as Potential
The Hydrophobic Effect 163 Cancer Treatments 199
A01_APPL1621_02_SE_FM.indd 6 17/11/17 5:14 PM
O
HO
NH
O
N
2 H O
N 12
N
N
Azidothymidine
N
N
N
DNA O NH N H O
Nevirapine N
O N H
H
N
HO
NH O
2
Saquinivir NH H
7.8 Oxygen Transport from Lungs to Tissues: Protein 8 HAIVz idreoCvtehorynsmete idtnriantnse s (cArZ|ip Tta) vsbeoiiund to
7.9 CFTauhnonedn c fOHotixeromymnga oetgnio2l-on0Bba0iinln dC ihna2gn0 S1giete Esn ihna Mncyeosg lobin CEBHnioAzlPyoTmgEiRec sa:l Catalysts 232 Fusion reNveevrisrea ptrinaen sbcoruipntdas teo HIV toS aHqIVu inpirvoirt ebaosuend
8.1 Enzymes As Biological
Analysis of Oxygen Binding by Myoglobin 203
Catalysts 234
7.10 The Role of Conformational Change
8.2 The Diversity of Enzyme HIV
in Oxygen Transport 204
Function 234
CMCA ohOoCoaxdlpnoyeeggslsreeea rsnft o LiiBvrno ei tonH hBkdee iiam nnAtdgol li tognhslgeo2t ebaA0rinl6nilcdo S sCAttehlrluroaicsncttg ueCerrhe yia nAn cHg2cee0o m4 mopgalonbyiinn g 206 8.3 CaRneahandecd mtt ihRoiceenaa ERcl ftaRfitoeeencas t,Ocs Rtr idoaoeftne rC CRaoat2nat3esl5ytsas n tsts , 235 Binding RVNirAalDNA insttyorRn aDtenhNveseAscrirzsiepest aRsNeA pcoPlleyrapovrteoestae vsinirea l Budding
7.11 Ailnlo Hsetemroicg lEofbfienc to2r0s8 of Hemoglobin FSiercsto-nOdr-dOerrd Reer aRcetaiocntsio ns2 35237 Translation Viral vMirioanture
PRCReaerosrsbppmoooonnn tssDeeei oEttxoofif dpCiceHhi l eToCrnrahitdna Oesnp gxIooeyrnsgt : e aTnth 2 teDh1 e2eB loαihv-Gre rlEoyfbf etinoc tT is2s1u1es 211 8.4 HTTrrtoaaownn Ess niiEttziinooyznnmy SSamtttaaiectts eeC s ATa ahctanetl doya rssRyis eAC apacpt2tail3oiel9nyd s R tast:e s 237 hvoiinrsIantt elt geDgegrNnaraoAtesm sieneto Transcription pVroirtaeli nRNA
N-Terminus 212 Principles and Examples 240
2,3-Bisphosphoglycerate 213 Models for Substrate Binding and Catalysis 241
Mechanisms for Achieving Rate Acceleration 241
7.12 Myoglobin and Hemoglobin as Examples of the
Case Study #1: Lysozyme 243
Evolution of Protein Function 214
Case Study #2: Chymotrypsin, a Serine Protease 245
The Structure of Eukaryotic Genes:
Exons and Introns 214 8.5 Coenzymes, Vitamins, and Essential Metals 248
7.13 Mechanisms of Protein Mutation 215 Coenzyme Function in Catalysis 248
Substitution of DNA Nucleotides 215 Metal Ions in Enzymes 249
Nucleotide Deletions or Insertions 216 8.6 The Kinetics of Enzymatic Catalysis 250
Gene Duplications and Rearrangements 216 Reaction Rate for a Simple Enzyme-Catalyzed Reaction:
Evolution of the Myoglobin–Hemoglobin Michaelis–Menten Kinetics 250
Family of Proteins 216 Interpreting K , k , and k /K 252
M cat cat M
7.14 Hemoglobin Variants and Their Inheritance: Enzyme Mutants May Affect kcat and KM Differently 253
Genetic Diseases 218 Analysis of Kinetic Data: Testing the
Pathological Effects of Variant Hemoglobins 218 Michaelis–Menten Model 253
7.15 Protein Function Requiring Large Conformational 8.7 Enzyme Inhibition 254
Changes: Muscle Contraction 220 Reversible Inhibition 254
Competitive Inhibition 254
7.16 Actin and Myosin 221
Uncompetitive Inhibition 256
Actin 221
Mixed Inhibition 258
Myosin 221
Irreversible Inhibition 259
7.17 The Structure of Muscle 223
Multisubstrate Reactions 260
7.18 The Mechanism of Contraction 223 Random Substrate Binding 260
Regulation of Contraction: The Role Ordered Substrate Binding 260
of Calcium 226 The Ping-Pong Mechanism 260
TOOLS OF BIOCHEMISTRY 7A Immunological Qualitative Interpretation of KM and Vmax: Application
Methods 230 to Multisubstrate Reaction Mechanisms 260
A01_APPL1621_02_SE_FM.indd 7 08/11/17 1:02 PM
viii | Contents
8.8 The Regulation of Enzyme Activity 262 Distinguishing Features of Different Disaccharides 289
Substrate-Level Control 262 Writing the Structure of Disaccharides 290
Feedback Control 262 Stability and Formation of the Glycosidic Bond 291
Allosteric Enzymes 263
9.4 Polysaccharides 292
Homoallostery 263
Storage Polysaccharides 293
Heteroallostery 264
Structural Polysaccharides 294
Aspartate Carbamoyltransferase: An Example of an
Cellulose 294
Allosteric Enzyme 264
Chitin 295
8.9 Covalent Modifications Used to Glycosaminoglycans 296
Regulate Enzyme Activity 266 The Proteoglycan Complex 296
Pancreatic Proteases: Activation by Irreversible Protein Nonstructural Roles of Glycosaminoglycans 296
Backbone Cleavage 267
Bacterial Cell Wall Polysaccharides; Peptidoglycan 297
8.10 Nonprotein Biocatalysts:
9.5 Glycoproteins 298
Catalytic Nucleic Acids 268
N-Linked and O-Linked Glycoproteins 298
TOOLS OF BIOCHEMISTRY 8A How to Measure the N-Linked Glycans 298
Rates of Enzyme-Catalyzed Reactions 273
O-Linked Glycans 298
FOUNDATION FIGURE Regulation of Enzyme Activity 276 Blood Group Antigens 299
Erythropoetin: A Glycoprotein with Both O- and N-Linked
Oligosaccharides 300
9
Lipoteichoic Influenza Neuraminidase, a Target
acid
CHAPTER
for Antiviral Drugs 300
Polysaccharide
coat
Carbohydrates:
TOOLS OF BIOCHEMISTRY 9A The Emerging Field
Sugars, Saccharides,
P(ceepll twidaolgl)lycan of Glycomics 303
Glycans 278
Lipid bilayer
membrane
Staphylococcus aureus
(Gram positive)
9.1 Monosaccharides 281 NAM NAG 10
NAM Teichoic
Aldoses and Ketoses 281 acid Integral CHAPTER
protein
Enantiomers 281 Tetrapeptide (gly)5 Lipids, Membranes, and
Alternative Designations for Cellular Transport 304
Peptidoglycan structure
Enantiomers: d–l and R–S 281
Monosaccharide Enantiomers in Nature 282 10.1 The Molecular Structure and
Diastereomers 282 Behavior of Lipids 306
Tetrose Diastereomers 282 Fatty Acids 306
Pentose Diastereomers 283 Triacylglycerols: Fats 308
Hexose Diastereomers 283 Soaps and Detergents 309
Leucine Na1 Nortriptyline
Aldose Ring Structures 283 Waxes 309 NH
Pentose Rings 283
10.2 The Lipid Constituents of Biological Membranes 309 INSIDE THE CELL
Hexose Rings 285
Glycerophospholipids 310
Sugars with More Than Six Carbons 287
Sphingolipids and Glycosphingolipids 311
9.2 Derivatives of the Monosaccharides 287 Glycoglycerolipids 312
Phosphate Esters 287 Cholesterol 312 OUTSIDE THE CELL
Lactones and Acids 288
10.3 The Structure and Properties of MembraneLesuci ne
Alditols 288 and Membrane Proteins 313 A bacterial Leucine/Na1 transporter AN ad1o pioanms inane dtr tahnes pnoeurtreort rbaonusnmdi tttoe rt wo
Amino Sugars 288 (model for dopamine transport across membranes) reuptake inhibitor Nortriptyline.
Motion in Membranes 314
Glycosides 288
Motion in Synthetic Membranes 314
9.3 Oligosaccharides 289 Motion in Biological Membranes 315
Oligosaccharide Structures 289 The Asymmetry of Membranes 315
A01_APPL1621_02_SE_FM.indd 8 08/11/17 1:02 PM
Contents | ix
Characteristics of Membrane Proteins 316 Energy Yields, Respiratory Quotients,
Insertion of Proteins into Membranes 317 and Reducing Equivalents 351
Evolution of the Fluid Mosaic Model ATP as a Free Energy Currency 352
of Membrane Structure 319 Metabolite Concentrations and Solvent Capacity 354
Thermodynamic Properties of ATP 355
10.4 Transport Across Membranes 321
The Important Differences Between ΔG and ΔG°′ 356
The Thermodynamics of Transport 321
Kinetic Control of Substrate Cycles 356
Nonmediated Transport: Diffusion 322
Other High-Energy Phosphate Compounds 357
Facilitated Transport: Accelerated Diffusion 323
Other High-Energy Nucleotides 358
Carriers 323
Adenylate Energy Charge 358
Permeases 324
Pore-Facilitated Transport 325 11.5 Major Metabolic Control Mechanisms 358
Ion Selectivity and Gating 326 Control of Enzyme Levels 358
Active Transport: Transport Against Control of Enzyme Activity 359
a Concentration Gradient 328 Compartmentation 359
10.5 Ion Pumps: Direct Coupling of ATP Hormonal Regulation 360
Hydrolysis to Transport 328 Distributive Control of Metabolism 361
10.6 Ion Transporters and Disease 330 11.6 Experimental Analysis of Metabolism 362
Goals of the Study of Metabolism 362
10.7 Cotransport Systems 331
Levels of Organization at Which Metabolism Is
10.8 Excitable Membranes, Action Potentials,
Studied 362
and Neurotransmission 332
Whole Organisms 362
The Resting Potential 332
Isolated or Perfused Organs 362
The Action Potential 333
Whole Cells 362
Toxins and Neurotransmission 334
Cell-Free Systems 363
FOUNDATION FIGURE Targeting Pain and Inflammation
Purified Components 363
through Drug Design 338
Systems Level 363
11 Metabolic Probes 363
CHAPTER TOOLS OF BIOCHEMISTRY 11A Metabolomics 367
Chemical Logic
TOOLS OF BIOCHEMISTRY 11B Radioactive
of Metabolism 340 and Stable Isotopes 370
FOUNDATION FIGURE Enzyme Kinetics
11.1 A First Look at
and Drug Action 372
Metabolism 342
11.2 Freeways on the Metabolic
12
Road Map 343
CHAPTER
Central Pathways of Energy Metabolism 343
Carbohydrate Metabolism:
Distinct Pathways for Biosynthesis and Degradation 346
Glycolysis, Gluconeogenesis,
11.3 Biochemical Reaction Types 347
Glycogen Metabolism, and
Nucleophilic Substitutions 347
the Pentose Phosphate
Nucleophilic Additions 348
Pathway 374
Carbonyl Condensations 348
Eliminations 350
12.1 An Overview of
Oxidations and Reductions 350
Glycolysis 377
11.4 Bioenergetics of Metabolic Pathways 350 Relation of Glycolysis to Other
Oxidation as a Metabolic Energy Source 350 Pathways 377
Biological Oxidations: Energy Release Anaerobic and Aerobic Glycolysis 377
in Small Increments 351 Chemical Strategy of Glycolysis 379
A01_APPL1621_02_SE_FM.indd 9 17/11/17 3:51 PM