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Textbook of Biochemistry With Clinical Correlations 7th Edition 7th Edition Ebook PDF
Textbook of Biochemistry With Clinical Correlations 7th Edition 7th Edition Ebook PDF
Thomas M. Devi in
Editor
Part I Part IV
STRUCTURE OF MACROMOLECULES METABOLIC PATHWAYS AND THEIR
CONTROL
1 Eukaryotic Cell Structure l
14 Bioenergetics,Mitochondria,
2 DNA and RNA:
and Oxidative Metabolism 541
Composition and Structure 25
15 Carbohydrate Metabolism I: Major Metabolic
3 Proteins I: Composition and Structure 75
Pathways and Their Control 591
16 Carbohydrate Metabolism II: Special Pathways and
Part II
Glycoconjugates 647
TRANSMISSION OF INFORMATION
17 Lipid Metabolism I: Synthesis, Storage,
4 DNA Replication, Recombination,
and Utilization of Fatry Acids
and Repair 139
and Triacylglycerols 673
5 RNA: Transcription and RNA Processing 181
18 Lipid Metabolism II: Pathways of Metabolism
6 Protein Synthesis:Translation and Posnranslational of Special Lipids 707
Modifications 209
19 Amino Acid and Heme Metabolism 751
7 Recombinant DNA and Biotechnology 255
20 Purine and Pyrimidine
8 Regulation of Gene Expression 303 Nucleotide Metabolism 807
21 Metabolic Interrelationships 839
Part Ill
22 Biochemistry of Hormo nes 883
FUNCTIONS OF PROTE INS
9 Proteins II: Structure-Function Relationships
Part V
in Protein Families 333
PHYSIOLOGICAL PROCESSES
10 Enzymes: Classification,Kinetics,
23 Molecular Cell Biology 939
and Control 377
24 Cell Cycle, Programmed Cell Death,
11 The Cytochromes P450 and Nitric
and Cancer 1003
Oxide Synthases 425
25 Digestion and Absorption of Basic
12 BiologicalMembranes: Structure, Receptors,
Nutritional Constituents 1029
and Solute Transport 457
26 Vitamins and Minerals:
13 Fundamentals of Signal Transduction 503
Requirements and Function 1063
27 Macronutrients: Metabolic Effects
and Health Implications 1101
2 DNA and RNA: Composition and Structure 25 3 Proteins I: Composition and Strucntre 75
Stephen A. Woski and Francis J. Schmid t Richard M. Schult2
7.7 BACTERIOPHAGE,
COSMID,AND YEASTCLONING 8.8 PREINITIA
TION COMPLEXIN EUKARYOTES:
VECTORSAND ANALYSISOF LONG STRETCHES TRANSCRIPTIONFACTORS,RNAPOLYMERASE TI,
OFDNA 277 ANDDNA 320
Bacteriophage as Cloning Vectors 277 Eukaryotic Promoters and Other Sequences
Cloning DNA Fragments into Cosmid and Artificial That Influence Transcription 321
Chromosome Vectors 278 Modular Design of Eukaryotic Transcription Factors 322
Subcloning Permits Definition of Large Segments of DNA 279 Common Motifs in Proteins That Bind DNA and Regulate
Chromosome Walking Defines Gene Arrangement in Long Transcription 322
Stretches of DNA 279 8.9 REGUIATION OF EUKARYOTIC GENE
7.8 EXPRESSIONVECTORSAND FUSION PROTEINS 281 EXPRESSION 325
Foreign Genes Expressed in Bacteria Allow Synthesis Regulating the Regulators 326
of Their Encoded Proteins 281 Activation of Transcription of the LDL Receptor Gene
Expression Vectors in Eukaryotic Cells 282 Illustrates Many Features Found in Eukaryotic Gene
7.9 SITE-DIRECTED MUTAGENESIS 284 Regulation 326
Role of DNA Flanking Regions Evaluated by Deletion Epigenetic Control of Gene Expression 328
and Insertion Mutations 284
Site-Directed Mutagenesis of a Single Nucleotide 284 Part Ill
7.10 APPLICATIONS OF RECOMBINANT DNA
TECHNOLOGIES 288 FUNCTIONS OF PROTEINS
Antisense Nucleic Acids in Research and Therapy 289
Molecular Techniques Applied to the Whole Animal 290
Recombinant DNA in Agriculture Has Commercial 9 Proteins II: Structure-Function
Impact 294 Relationships in Protein Families 333
7.11 GENOMICS,PROTEOMICS,AND MICROARRAY
ANALYS
IS 295 Richard M. Schultz.
Microarray Analysis 296
Human Genome 298 KEYCONCEPTS
9.1 INTRODUCTION 334
9 .2 ANTIBODY MOLECULES: THE IMMUNOGLOBULIN
8 Regulation of Gene Expression 303 SUPERFAMILYOF PROTEINS 334
Antibody Molecules Contain Four Polypeptide Chains 335
Daniel L. Weeks and John E. Donelson lmmunoglobullns in a Class Contain Homologous
CH Regions 338
KEYCONCEPTS There Are Two Antigen-Binding Sites per Antibody
8.1 INTRODUCTION 304 Molecule 340
8.2 UNIT OF TRANSCRIPTION IN BACTERIA: Genetics of the lmmunoglobulins 342
THE OPERON 304 lmmunoglobulin Fold Is Found In a Large Family of Proteins
with Different Functional Roles 343
8.3 IACTOSE OPERON OF E. COLI 305
Repressor of Lactose Operon Is a Diffusible Protein 306 9.3 PROTEINS WITH A COMMON CATALYTIC
Operator Sequence of Lactose Operon Is Contiguous MECHANISM: SERINE PROTEASES 343
with a Promoter and Three Structural Genes 307 Proteolytic Enzymes Are Classified by Their Catalytic
RNAPolymerase and a Regulator Protein Recognize Mechanism 343
Promoter Sequence of Lactose Operon 309 Serine Proteases Are Synthesized as Zymogens and in
Catabolite Activator Protein Binds Lactose Multiple Domain Proteins 347
Promoter 309 Tertiary Structures of the Catalytic Domains of Serine
Proteases Are Similar 348
8.4 TRYPTOPHANOPERONOF E. COLI 310
Serine Proteases Have Similar Structure-Function
Tryptophan Operon Is Controlled by a Repressor
Relationships 350
Protein 310
Sequence Homology in Serine Proteases 351
Attenuator Region of Tryptophan Operon 312
Mechanism of Serine Protease Catalysis 352
Transcription Attenuation Controls Other Operons for Amino
Specific Protein Inhibitors of Serine Proteases 352
Acid Biosynthesis 313
9.4 HEMOGLOBIN AND MYOGLOBIN 353
8.5 OTHERBACTERIAL
OPERONS 314
Human Hemoglobin Occurs in Several Forms 353
Synthesis of Ribosomal Proteins Is Regulated
Myoglobin: A Single Polypeptide with One 0 2 -Binding
in a Coordinated Manner 314
Site 354
Stringent Response Controls Synthesis of rRNAs
The Heme Prosthetic Group Is Site of 0 2 Binding 355
and tRNAs 3 I 5
X-Ray Crystallography Has Defined the Structures
8.6 BACTERIALTRANSPOSONS 316 of Hemoglobin and Myoglobin 355
Transposons Are Mobile Segments of DNA 316 A Simple Equilibrium Defines 0 2 Binding to Myoglobin 357
Transposon Tn3 Contains Three Structural Binding of 0 2 to Hemoglobin Involves Cooperalivity
Genes 316 between Subunits 358
8.7 GENE EXPRESSION IN EUKARYOTES 317 Hemoglobin Facilitates Transport of CO2 and NO 360
Eukaryotic DNA Is Bound by Histones to Form Decrease in pK8 of Acid Groups with Change from T to R
Chromatin 317 Conformation Releases Protons 360
Methylation of DNA Correlates with Gene Hemoglobin Delivers Nitric Oxide (NO) to the Capillary Wall
Inactivation 319 of Tissues Where It Promotes 0 2 Delivery 366
CONTENTS • xiii
9.5 THE BASAL LAMINA PROTEIN COMPLEX 367 10.11 REGULATIONOF METABOLICPATHWAYS 417
Protein Composition of the Basal Lamina 368 10.12 CLINICALAPPLICATIONS
OFEN2YMES 418
The Molecular Structure of Basal Lamina Is Formed Measurement of Plasma Enzymes 418
from Networks of Laminin and Type IV Collagen 369 Metabolomics and Proteomics 420
Focal Contact in Cell Membrane Interconnects Extracellular
Matrix with Cytoskeleton 373
11 The Cytochromes P450 and Nitric
10 Enzymes: Classification, Kinetics, Oxide Synthases 425
and Control 377
Linda). Roman and Bertie Sue Siler Masrers
Henry Weiner
KEYCONCEPTS
KEYCONCEPTS 11.1 INTRODUCTION 426
10.1 INTRODUCTION 378 11.2 CYTOCHROMES P4S0:PROPERTIES
AND FUNCTION 426
10.2 CLASSIFICATIONS
OF EN2YMES 378 11.3 CYTOCHROMEP4S0 ELECTRON TRANSPORT
Class 1: Oxidoreductases 379
SYSTEMS 427
Class 2: Transferases 380
NADPH-Cytochrome P450 Reductase Is the Obligatory
Class 3: Hydrolases 380
FlavoproteinElectronDonor in the EndoplasmicReticulum 428
Class 4: Lyases 380
NADPH-Adrenodoxin Reductase ls the Flavoprotein Electron
Class 5: lsomerases 381
Donor in Mitochondria 430
Class 6: ligases 382
11.4 CYTOCHROMESP4S0:
10.3 GENERAL CONCEPTS OF EN2YME
NOMENCLATURE AND ISOFORMS 430
MECHANISMS 382
Thermodynamic Considerations 382 11.5 CYTOCHROME$ P4S0: SUBSTRATES AND
Binding of Substrate by an Enzyme 383 PHYSIOLOGICAL FUNCTIONS 431
Transition State 383 Cytochromes P450 Participate in the Synthesis of
Covalent Binding of Substrate to Enzyme 386 Steroid Hormones and Oxygenation of Endogenous
pH Alters a Reaction by Affecting General Acids and Bases 387 Compounds 432
10.4 ACTIVESITEOFANEN2YME 387 Cytochromes P450 Oxidize Exogenous Upophilic
Stereochemistry of Active Site 388 Substrates 436
Influence of Groups on the Substrate Distal to the Bond 11.6 CYTOCHROMEP450: INDUCTION AND
Being Modified 388 INHIBITION 440
10.5 COEN2YMES, CO-SUBSTRATES, AND COFACTORS 390 Drug-Drug Interactions 440
Coenzymes 390 Cytochrome P450 Genetic Polymorphisms 442
Adenosine Triphosphate May Be a Second Substrate Therapeutic Inhibition of Cytochrome P450 444
or a Modulator of Activity 393 11.7 NITRIC OXIDE SYNTHASES: PROPERTIES AND
Metal Ion Cofactors 393 EN2YMA TIC FUNCTION 444
10.6 KINETICS OF CHEMICAL REACTIONS 395 11.8 NITRICOXIDESYNTHASEISOFORMS
Rate of Product Formation 395 AND PHYSIOLOGICAL FUNCTIONS 447
Rate of Substrate Disappearance 396 NOSI 447
Reversible Reactions 397 NOSII 448
10.7 EN2YME KINETICS OF ONE-SUBSTRATE NOSIII 450
REACTIONS 397
Michaelis-Menten Equation 400
Significance of f<cat
in the Michaelis-Menten Equation 402 12 Biological Membranes: Structure,
Low Km versus High f<ca
1 403 Receptors, and Solute Transport 457
Calculating the Constants 404
Effect of Assay Conditions 404 Thomas M. Devlin
10.8 KINETICS OF TWO-SUBSTRATE REACTIONS 405
Sequential Mechanism 405 KEYCONCEPTS
Ping-Pong Mechanism 405 12.1 INTRODUCTION 458
Kmaw 407 12.2 CHEMICAL COMPOSITION OF MEMBRANES 458
10.9 INHIBITORS 407 Lipids Are Major Components of Membranes 458
Competitive Inhibition 407 Glycerophospholipids Are the Most Abundant lipids
Uncompetitive Inhibition 408 of Membranes 458
Noncompetitive Inhibition 408 Sphingolipids Are Present in Membranes 460
Lineweaver-Burk Plots in the Presence of Inhibitors 409 Cholesterol Is an Important Component of Plasma
Other Inhibitors 410 Membranes 462
Enzyme Inhibitors as Drugs 41 l Lipid Composition Varies between Membranes 462
Membrane Proteins 463
10.10 REGUIATIONOFEN2YMEACTMTY 413
Membrane Carbohydrates Are Part of Glycoproteins
Covalent Modification 413
Allosteric Control of Enzyme Activity 413 or Glycolipids 463
Multi-subunit Enzymes: Cooperativity 414 12.3 MICELLES, LIPID BILAYERS,AND LIPOSOMES 463
Regulatory Subunits Modulate the Activity of Catalytic Lipids Form Vesicular Structures 463
Subunits 417 General Properties of Lipid Bilayers 465
xiv • CONTENTS
Part IV
13 Fundamentals of Signal T ransduction 503
METABOLICPATHWAYSAND THEIR CONTROL
George R. Dubyak
Part V
PHYSIOLOGICALPROCESSES
25 Digestion and Absorption
of Basic Nutritional Consrimenrs 1029
23 Molecular Cell Biology 939 Ulr ich Hopfer
Thomas E. Smith
KEYCONCEPTS
25.1 INTRODUCTION 1030
KEYCONCEPTS Nutrient Types 1030
23 .1 NERVOUS TISSUE: Several Gastrointestinal Organs Contribute to Food
Digestion 1030
METABOLISM AND FUNCTION 940
Essential Concepts 940 25.2 GENERAL CONSIDERATIONS 1032
ATP and Transmembrane Electrical Potential In Neurons 942 Different Sites of Digestion 1032
Neuron-Neuron Interaction Occurs through Synapses 943 Digestive Enzymes Are Secreted as Proenzymes 1033
Synthesis, Storage, and Release of Neurotransmitters 945 Secretion Is Regulated by Many Secretagogues 1033
Termination of Signals at Synaptic Junctions 948 25 .3 EPITHELIAL TRANSPORT 1036
Neuropeptides Are Derived from Precursor Proteins 951 Solute Transport May Be Transcellular or Paracellular 1036
CONTENTS • xix
NaCl Absorption Depends on Na+tK+-exchanging ATPase, Iodine Is Incorporated Into Thyroid Hormones 1091
Membrane Transporters, and Channels 1037 Zinc Is Required by Many Proteins 1091
NaCl Secretion Depends on Na+fK +-exchanging ATPase , Copper Is a Cofactor for Important Enzymes 1092
Membrane Transporters, and Channels 1039 Chromium Is a Component of Chromodulin 1093
Ion Concentration Gradients and Electrical Potentials Selenium Is Found in Selenoprote ins 1093
Energize Transport of Nutrients 1041 Manganese , Molybdenum , Fluoride , and Boron Are Essential
Gastric Parietal Cells Secrete HCI 1042 Trace Elements 1094
25.4 DIGESTION AND ABSORPTION OF PROTEINS 1043 26.11 THE AMERICANDIET:FACTAND FALLACY 1094
Peptidases Assure Efficient Protein Digestion 1043 26 .12 ASSESSMENTOF NUTRITIONALSTATUS
Amino Acid and Di- and Tripeptide Transporters 1046 IN CLINICALPRACTICE 1094
25.5 DIGESTION AND ABSORPTION 26 .13 NUTRIGENOMICS-THEFUTUREOFNUTRITION 1095
OF CARBOHYDRATES 1049
Disaccharides and Polysaccharides Require Hydrolysis 1049
Monosaccharide Transporters 1051
25.6 DIGESTIONAND ABSORPTIONOF LIPIDS 1051
27 Macronutrienrs: Metabolic Effects
Digestion of Lipids Requires Overcoming Their Limited and Health Implications 1101
Water Solubility 1051 Stephen G. Chaney
Lipids Are Digested by Gastric and Pancreatic Lipases 1052
Bile Acid Micelles Solubilize Lipids during Digestion 1053 KEYCONCEPTS
Most Absorbed Lipids Are Incorporated into Chylomicrons 1057
27.1 INTRODUCTION 1102
25.7 BILE ACID METABOLISM 1058
Bile Acid Chemistry and Synthesis 1058 27.2 ENERGYMETABOLISM 1102
Bile Acid Transport 1058 Energy Content of Food Is Measured Primarily
in Kilocalories 1102
Energy Expenditure Is Influenced by Four Factors 1102
26 Vitamins and Minerals: 27.3 PROTEINMETABOLISM 1103
Dietary Protein Serves Many Roles Including Energy
Requirements and Function 1063 Production 1103
Nitrogen Balance Relates Intake to Excretion of Nitrogen 1103
Stephen G. Chaney Essential Amino Acids Must Be Present in the Diet 1103
Protein Sparing Is Related to Dietary Content
KEYCONCEPTS
of Carbohydrate and Fat 1104
26 .1 INTRODUCTION 1064 Normal Adult Protein Requirements 1104
26.2 ASSESSMENTOF MALNUTRITION 1064 Protein Requirements Are Increased during Growth
26.3 DIETARYREFERENCEINTAKES 1065 and Illness 1106
26 .4 FAT-SOLUBLE
VITAMINS 1065 27.4 PROTEIN-ENERGY MALNUTRITION 1107
Vitamin A Is Derived from Plant Carotenoids 1065 27.5 EXCESS PROTEIN-ENERGY INTAKE 1107
Vitam in D Synthesis Requires Sunlight 1067 Obesity Has Dietary and Genetic Components 1107
Vitamin E Is a Mixture of Tocopherols and Tocotrienols 1072 Obesity , Insulin Resistance, Metabolic Syndrome ,
Vitamin K Is a Quinone Derivative 1073 and Type 2 Diabetes 1108
26.5 WATER-SOLUBLE VITAMINS 1075 Obesity Has Significant Health Implications 1110
7.13 Transgenic Animal Models 292 11.7 Genetic Polymorphisms of NADPH-Cytochrome P450
7. 14 Knockout Mice to Define a Role for the P2Y1 Reductase: Antley-Bix ler Syndrome 443
Purinoceptor 293 11.8 Mechanism of Action of Sildenafil 449
7.15 Microarray Techniques to Detect and Treat Diseases 296 11.9 Nitric Oxide Overproduct ion in Septic Shock 450
11.10 History and Biological Effects of Nitroglycerin 451
11.11 Therapeutic Uses of Inhaled Nitric Oxide 452
11. 12 The Role of eNOS in Endothelial Dysfunction 452
8 Regulation of Gene Expression
8.1 Transmissible Multiple-Drug Resistance 316
8.2 The Bacterial Pathogen of the Stomach: Helicobacter
pylori 317
12 Biological Membranes : Structu re,
8.3 Rubinstein-Taybi Syndrome 319 Recepcors, and Solute Transport
8.4 Tamoxifen and Targeting of Estrogen Receptor 326 12.1 Liposomes as Carriers of Drugs, Proteins, and Nucleic
8.5 Transcription Factors and Cardiovascular Disease 326 Acids 466
8.6 Cancer Treatment Using Drugs That Target Histone and DNA 12.2 Abnormalities of Cell Membrane Fluidity in Disease 472
Modification: Epigenetic Therapy 328 12.3 The Mammalian Kidney and Aquapor ins 480
12.4 Diseases due to Loss of Membrane Transport Systems 488
12.5 Cystic Fibrosis and the c 1- Channel 496
9 Proteins II : Structure-F unct ion 12.6 Diseases Involving the Superfamily of ABC
Relationships in Protein Families Transporters 497
23.9 Familial Hypertropic Cardiomyopath ies and Mutations in 25.10 Cholesterol Absorption 1057
Muscle Proteins 971 25.11 A-/3-Upoproteinemia 1058
23.10 Dilated Card iomyopathy and Mutations in Actin 972
23.11 Troponin Subunits as Markers for Myocardial Infarction 974
23.12 Ion Channels and Cardiac Muscle Disease 978
23.13 Mutations Affecting Pigmentation: Is There a Molecular
26 Vitamins and Minerals:
Motor Connection? 980 Requirements and Func tion
23.14 Intrinsic Pathway Defects: Prekallikrein Deficiency 985 26.1 Nutritional Considerations in Cystic Fibrosis 1068
23.15 Classic Hemophilia 990 26.2 Renal Osteodystrophy 1070
23.16 Use of Recombinant Factor VIia to Control Bleeding 990 26.3 Nutritional Considerations in Newborn Infants 1074
23.17 Thrombosis: Defects of the Protein C Pathway and Increased 26.4 Anticonvulsant Drugs and Vitamin Requirements 1075
Levels of Coagulation Factors 993 26.5 Nutritional Considerations in Alcoholics 1076
26.6 Gene Polymorphisms and Folic Acid Requirement 1082
26.7 Nutritional Needs of Elderly Persons 1083
24 Cell Cycle, Program med Ce ll 26.8 Diet and Osteoporosis 1086
26.9 Ceruloplasmin and Iron Metabolism 1089
Death and Cance r 26.10 Hemochromatosis 1090
24.1 Oncogen ic DNA Viruses IO 17 26.11 Clinical Tests for Iron-Deficiency Anemia
24.2 Molecularly Targeted Anticancer Drug 1021 and Hemochromatosis 1091
24.3 Environmental Cause of Human Cancers 1022 26.12 Diseases of Copper Metabolism 1093
6 Prote in Synthesis: Transla tion and 19 Amino Acid and Heme Metabolism
Posttranslational Modifications 19.1 Blood Urea Nitrogen and Measurementof Nitrogen Balance 753
6.1 Aminoacyl-tRNA Synthetases 212 19.2 Mechanism of Aminotransferases 754
6.2 Ribosome Structure and Function 218 19.3 lntercellular Glutamine Cycle 759
6.3 Chaperones of the Endoplasmic Reticulum 232 19.4 Pyruvoyl Enzymes 765
6.4 Ubiquitin and SUMO 251 19.5 Tryptophan, Carbohydrates, and Sleep 775
19.6 Lysine and Pipecolate 778
19.7 Urochrome 800
topic. As in previous editions, there is frequent cross-referencing carbohydrates (Chapter 15), and special pathways of carbohy-
between chapters . drates and glycoconjugates (Chapter 16). This is followed by a
chapter covering the synthesis, storage, and utilization of energy
in lipid form (Chapter 17), then one describing the metabolism
New Features in the Seventh Edition
of phospholipids , sphingolipids, cholesterol, and prostaglandins
To facilitate the students' learning, we have added several new features (Chapter 18). Amino acid and heme metabolism are covered in
to the text. Chapter 19, followed by the synthesis and degradation of the
purine and pyrimidine nucleotides (Chapter 20). A chapter on
Key Concepts: A list of Key Concepcs appears at the beginning
the integration of these metabolic pathways in humans completes
of each chapter for srudencs to use as a guide while srudying
this part (Chapter 21). A major emphasis throughout Part N is
the chapter and as a reference for self-evaluation at completion
on the controls of each pathway or process.
of study.
Part V, Physiological Processes, covers those areas unique
A Closer Look: These boxes contain supplementary information
to mammalian cells and tissues beginning with a chapter on
on the topic under discussion.
hormones that emphasizes their biochemical functions as mes-
Key Terms:A list of Key T errns appears at the end of each
sengers (Chapter 22) and a chapter on molecular cell biology
chapter;
containing discussions of four major physiological signal-trans-
Online Mendelian Inheritance in Man (OMIM):
ducing systems: the nervous system, the eye, muscle contraction
Accession numbers associated with a disease or enzyme in the
and molecular motors, and blood coagulation (Chapter 23) . A
Online Mendelian Inheritance in Man (OMIM) database are
discussion of the cell cycle, programmed cell death , and cancer,
indicated at appropriate places in the text. The OMIM database
three closely related topics, is presented (Chapter 24). A chapter
(www.ncbi.nlm .nih.gov/Omim) catalogues known diseases with
on the complex and integrated biochemistry of digestion and
a genetic component .
absorption of basic nutritional constituents (Chapter 25) is
followed by one on the functions and nutritional requirements
of vitamins and minerals in metabolism (Chapter 26) . The last
Content and Organization of the Seventh Edition
chapter covers the general principles of human nutrition for
The content of the seventh edition is divided into five major pares. proteins , carbohydrates, and fats (Chapter 27).
Part I, Structureof Macromolecules, contains an introduc- A Glossary with precise definitions serves as a ready reference to
tory chapter on eukaryotic cell structure (Chapter 1), followed the most common words in the ever-expanding language of the
by two chapters on the chemistry and structure of nucleic acids biochemical sciences. New terms have been added to enrich this
(Chapter 2) and protein (Chapter 3). section.
Part II, Transmission of Information, begins with separate chap- A Review of Organic Chemistry, as an Appendix , is designed
ters on the synthesis of the major cellular macromolecules, that is, as a ready reference for the nomenclature and structures of important
DNA (Chapter 4), RNA (Chapter 5), and proteins (Chapter 6). organic molecules encountered in biochemistry; it is not intended
A chapter on recombinant DNA and biotechnology is included as a comprehensive review. The reader should become familiar with
because the knowledge and techniques in this area have had and the content of the Appendix so that it can be used when necessary
continue to have a profound impact on research in nearly all facets while reading the main text.
of biochemistry (Chapter 7). Part II concludes with a chapter on Clinical Correlations boxes in every chapter describe examples
the Regulation of Gene Expression in which mechanisms of both of human diseases where the ramifications of deviant biochemical
prokaryotes and eukaryotes are presented (Chapter 8). processes are well established. There are 260 Clinical Correlations
Part III, Functions of Proteins, opens with a presentation of presenting the aberrant biochemistry of very common to relatively
the structure-function relationship of four major families of rare medical conditions, and in some cases their treatment based on
proteins, that is, antibody molecules, serine proteases, hemo- the biochemical knowledge of the condition. The presentations are
globin, and basal lamina proteins (Chapter 9). This is fol- discussions of the altered biochemistry rather than a medical case
lowed by a detailed discussion of enzyme function and kinetics study. In some instances, the same clinical condition is presented
(Chapter 10) and a separate chapter on the cytochromes P450, in different chapters, but each time it is based on the biochemistry
a unique and important family of enzymes (Chapter 11). A being presented . In the case of several major diseases, as example
chapter on membrane structure and the essentials of transmem- diabetes, a single Clinical Correlation is designated as the primary
brane transport mechanisms (Chapter 12), and a chapter on discussion and other Correlations on the same disease cite the pri-
the basic mechanisms of cellular signal transduction conclude mary one for general background information. An understanding
Part III (Chapter 14). These chapters present the fundamentals of the material in the main text does not require a reading of the
of these topics and subsequent chapters present their role in Clinical Correlations . References are included in the Correlations
specific cellular processes. to facilitate exploration of the topic in more detail. In a few cases,
Part IV, Metabolic Pathways and Their Control, opens with clinical conditions are discussed as part of the primary text because
a chapter on bioenergetics and oxidative metabolism (Chapter studies of the medical condition have lead to an understanding of a
14). Separate chapters describe the major metabolic pathways of basic biochemical process.
PREFACE • xxix
Supplements in the subject presented in the chapter that he or she has written.
They prepared their chapters from the perspective of the classroom
The Textbookof Biochemistrywith Clinical Corre/4tions,7e offers instructor , with the experience to select the topics and determine the
a variety of innovative resources to support both students and emphasis required for students in a general biochemisrry course.
instruct0rs: Every contributor brings to the book an individual approach ,
For students leading co some differences in presentation. Every chapter, however,
Guided Explorations . 50 self-contained presentations, many with was edited to have a consistent writing sryle and to eliminate unnec-
narration, employing extensive animated computer graphics t0 essary repetitions and redundancies. A few t0pics are discussed in
enhance student understanding of key t0pics. two different places in the book in order to make the individual
Interactive Exercises. 22 molecular structures that have been ren- discussions complete and self-contained. This repetition should
dered in J mol, a browser-independent interface for manipulating facilitate the learning process.
structures in three dimensions, and paired with questions to facili- The textbook is not intended as a compendium of biochemical
tate comprehension of concepts. facts or a review of the current literature, but each chapter con-
Animated Figures. 25 figures illustrating various concepts , tech- tains sufficient detail on the subject co make it useful as a resource.
niques, and processes; presented as brief animations that serve as Conrribut0rs were requested not to reference individual researchers
helpful learning tools. and not to dwell on the historical aspeccs of their topic; our apolo-
gies to the many scientists who deserve recognition for their out-
For instructors standing research contributions that have made chis book possible.
PowerPoint Slides: Includes all of the figures in the text. One person must accept the responsibility for the final product
Image Gallery:All of the figures in the text in JPEG format. in any project. The decisions concerning the selection of topics and
Test Bank: Over 2,700 multiple choice questions, many derived format and reviewing the drafts and the responsibility for the final
from question banks compiled by the Association of Medical and checking of the book were entirely mine. I accept full responsibility for
Graduate Departments of Biochemistry. these decisions. I welcome comments , criticisms, and suggestions from
students, faculty, and professionals. It is our hope that chis work will
In Conclusion be of value to those embarking on the exciting experience oflearning
about the chemistry oflife for the first time, as well as to those return-
As in previous editions, this work is a multiconrributor textbook. ing to a topic in which the information is expanding so rapidly.
Each contributor holds a senior academic rank, and they are all
members of the faculties of different universities. All of the contribu- THOMAS M. DEVLIN
tors have been involved actively in teaching biochemistry in a gradu- Berwyn, Pennsylvania
ate and/or medical program and each has an active research interest September2009
This page intentionally left blank
CAROL N. ANGSTADT, PH.D. DAVID w. CRABB, M.D. ROBERT H. GLEW,PH.D.
ProfessorEmerita John B. Hickam Professor Professor Emeritus
School of Nursing and Health Professions and Chair Department of Biochemistry
Drexel University Deparcmencsof Medicine and Molecular Biology
490 S. Old Middletown Road Professor, Department of Biochemistry MSC08 4670
Media, PA 19063 and Molecular Biology University of New Mexico
Email: cnang@veriztm.net Emerson Hall 317 Albuquerque, NM 87131
Indiana University School Email: rglew@saludunm.edu
DIANAs.BEATIIE, PH.D. of Medicine
Professorand Former Chair 545 Barnhill Drive DOHNG. GLITZ,PH.D.
Department of Biochemistry Indianapolis, IN 46202-5124 ProfessorEmeritus
West Virginia University School of Medicine Email:dcrabb@iupui.edu Department of BiologicalChemistry
PO Box 9142 UCLA School of Medicine
Morgantown, WV 26506 THOMAS M. DEVLIN, PH.D. 11260 Barnett Valley Road
wvu. edtt
E-mail: dbeattie@hsc. ProfessorEmeritus and Former Chair Sebastopol, CA 95472
Department of Biochemistry E-mail: dglitz@mednet.ucla.edu
STEPHEN G. CHANEY, PH.D. and Molecular Biology
Professor Drexel University College of Medicine RICHARDW. HANSON, PH.D.
Deparcmencsof Biochemistryand Biophysics 159 Greenville Court Leonard & Jean SkeggsProfessor
and of Nutrition Berwyn, PA 19312-2071 of Biochemistry
Genetic Medicine Building Email: tdevlin@drexelmededu Department of Biochemistry
School of Medicine CB# 7260 Room W414
University of North Carolina ac Chapel Hill JOHNE. DONELSON, PH.D. Case School of Medicine
Chapel Hill, NC 27599-7260 Professorand Former Chair Case Western ReserveUniversity
Email: stephen_chaney@med .ttnc.edtt Department of Biochemistry Cleveland, OH 44106-4935
Carver College of Medicine E-mail: rwh@cwru.edu
MARGUERITE W. COOMES, PH.D. University ofiowa
AssociateProfessor Bowen ScienceBuilding ROBERT A. HARRIS, PH.D.
Department of Biochemistryand Molecular Iowa City, IA 52242-0001 Distinguished ProfessorEmeritus
Biology EmaiL·john-donelson@uiowa .edu and Showalter Professor
Howard Universiry College of Medicine of Biochemistry Emerirus
3411 Murdock Road, GEORGE R. DUBYAK, PH.D. Deparcment of Biochemistry
Kensington, MD 20895-1630 Professor and Molecular Biology
Email: mcoomes@howardedu Department of Physiology Indiana University School
and Biophysics of Medicine
ANNH. CoRY,M.S. Case School of Medicine Richard Roudebush VA
ResearchAssociate Case Western ReserveUniversity Medical Center
Deparcment of Biochemistryand Molecular 2109 Adelbert Road Research 151; Room D-3034
Biology Cleveland, OH 44106 1481 West Tench Street
Brody School of Medicine Email:george.dubyak@case.edu Indianapolis, IN 46202
EaseCarolina Universiry Email· raharris@iupui.ed1,
Greenville, NC 27834-4354 HOWARD J. EDENBERG, PH.D.
Email: corya@ecu.edu Chancellor's Professor, Professorof ULRICH HOPFER, M.D., PH.D.
Biochemistryand Molecular Biology Professorof Physiology and Biophysics
JOSEPH G. CORY,PH.D. and of Medical and Molecular and Medicine
Professorand Former Chair Genetics Deparcment of Physiology
Department of Biochemistryand Molecular Department ofBiochemistty and Molecular and Biophysics
Biology Biology Case School of Medicine
Brody School of Medicine Indiana University School of Medicine Case Western ReserveUniversity
EaseCarolina Universiry 635 Barnhill Drive, Med. Sci. 4063 l 09000 Euclid Ave.
Greenville, NC 27858-4354 Indianapolis, IN 46202-5122 Cleveland, OH 44106-4970
Email· coryjo@ecu.edu Email: edenberg@iupui .edu Email· ulrich.hopfer@case
.ed1,
xxxii • CONTRIBUTORS
I see increasing reason to believe that the view formed some time
back as to the origin of the Makonde bush is the correct one. I have
no doubt that it is not a natural product, but the result of human
occupation. Those parts of the high country where man—as a very
slight amount of practice enables the eye to perceive at once—has not
yet penetrated with axe and hoe, are still occupied by a splendid
timber forest quite able to sustain a comparison with our mixed
forests in Germany. But wherever man has once built his hut or tilled
his field, this horrible bush springs up. Every phase of this process
may be seen in the course of a couple of hours’ walk along the main
road. From the bush to right or left, one hears the sound of the axe—
not from one spot only, but from several directions at once. A few
steps further on, we can see what is taking place. The brush has been
cut down and piled up in heaps to the height of a yard or more,
between which the trunks of the large trees stand up like the last
pillars of a magnificent ruined building. These, too, present a
melancholy spectacle: the destructive Makonde have ringed them—
cut a broad strip of bark all round to ensure their dying off—and also
piled up pyramids of brush round them. Father and son, mother and
son-in-law, are chopping away perseveringly in the background—too
busy, almost, to look round at the white stranger, who usually excites
so much interest. If you pass by the same place a week later, the piles
of brushwood have disappeared and a thick layer of ashes has taken
the place of the green forest. The large trees stretch their
smouldering trunks and branches in dumb accusation to heaven—if
they have not already fallen and been more or less reduced to ashes,
perhaps only showing as a white stripe on the dark ground.
This work of destruction is carried out by the Makonde alike on the
virgin forest and on the bush which has sprung up on sites already
cultivated and deserted. In the second case they are saved the trouble
of burning the large trees, these being entirely absent in the
secondary bush.
After burning this piece of forest ground and loosening it with the
hoe, the native sows his corn and plants his vegetables. All over the
country, he goes in for bed-culture, which requires, and, in fact,
receives, the most careful attention. Weeds are nowhere tolerated in
the south of German East Africa. The crops may fail on the plains,
where droughts are frequent, but never on the plateau with its
abundant rains and heavy dews. Its fortunate inhabitants even have
the satisfaction of seeing the proud Wayao and Wamakua working
for them as labourers, driven by hunger to serve where they were
accustomed to rule.
But the light, sandy soil is soon exhausted, and would yield no
harvest the second year if cultivated twice running. This fact has
been familiar to the native for ages; consequently he provides in
time, and, while his crop is growing, prepares the next plot with axe
and firebrand. Next year he plants this with his various crops and
lets the first piece lie fallow. For a short time it remains waste and
desolate; then nature steps in to repair the destruction wrought by
man; a thousand new growths spring out of the exhausted soil, and
even the old stumps put forth fresh shoots. Next year the new growth
is up to one’s knees, and in a few years more it is that terrible,
impenetrable bush, which maintains its position till the black
occupier of the land has made the round of all the available sites and
come back to his starting point.
The Makonde are, body and soul, so to speak, one with this bush.
According to my Yao informants, indeed, their name means nothing
else but “bush people.” Their own tradition says that they have been
settled up here for a very long time, but to my surprise they laid great
stress on an original immigration. Their old homes were in the
south-east, near Mikindani and the mouth of the Rovuma, whence
their peaceful forefathers were driven by the continual raids of the
Sakalavas from Madagascar and the warlike Shirazis[47] of the coast,
to take refuge on the almost inaccessible plateau. I have studied
African ethnology for twenty years, but the fact that changes of
population in this apparently quiet and peaceable corner of the earth
could have been occasioned by outside enterprises taking place on
the high seas, was completely new to me. It is, no doubt, however,
correct.
The charming tribal legend of the Makonde—besides informing us
of other interesting matters—explains why they have to live in the
thickest of the bush and a long way from the edge of the plateau,
instead of making their permanent homes beside the purling brooks
and springs of the low country.
“The place where the tribe originated is Mahuta, on the southern
side of the plateau towards the Rovuma, where of old time there was
nothing but thick bush. Out of this bush came a man who never
washed himself or shaved his head, and who ate and drank but little.
He went out and made a human figure from the wood of a tree
growing in the open country, which he took home to his abode in the
bush and there set it upright. In the night this image came to life and
was a woman. The man and woman went down together to the
Rovuma to wash themselves. Here the woman gave birth to a still-
born child. They left that place and passed over the high land into the
valley of the Mbemkuru, where the woman had another child, which
was also born dead. Then they returned to the high bush country of
Mahuta, where the third child was born, which lived and grew up. In
course of time, the couple had many more children, and called
themselves Wamatanda. These were the ancestral stock of the
Makonde, also called Wamakonde,[48] i.e., aborigines. Their
forefather, the man from the bush, gave his children the command to
bury their dead upright, in memory of the mother of their race who
was cut out of wood and awoke to life when standing upright. He also
warned them against settling in the valleys and near large streams,
for sickness and death dwelt there. They were to make it a rule to
have their huts at least an hour’s walk from the nearest watering-
place; then their children would thrive and escape illness.”
The explanation of the name Makonde given by my informants is
somewhat different from that contained in the above legend, which I
extract from a little book (small, but packed with information), by
Pater Adams, entitled Lindi und sein Hinterland. Otherwise, my
results agree exactly with the statements of the legend. Washing?
Hapana—there is no such thing. Why should they do so? As it is, the
supply of water scarcely suffices for cooking and drinking; other
people do not wash, so why should the Makonde distinguish himself
by such needless eccentricity? As for shaving the head, the short,
woolly crop scarcely needs it,[49] so the second ancestral precept is
likewise easy enough to follow. Beyond this, however, there is
nothing ridiculous in the ancestor’s advice. I have obtained from
various local artists a fairly large number of figures carved in wood,
ranging from fifteen to twenty-three inches in height, and
representing women belonging to the great group of the Mavia,
Makonde, and Matambwe tribes. The carving is remarkably well
done and renders the female type with great accuracy, especially the
keloid ornamentation, to be described later on. As to the object and
meaning of their works the sculptors either could or (more probably)
would tell me nothing, and I was forced to content myself with the
scanty information vouchsafed by one man, who said that the figures
were merely intended to represent the nembo—the artificial
deformations of pelele, ear-discs, and keloids. The legend recorded
by Pater Adams places these figures in a new light. They must surely
be more than mere dolls; and we may even venture to assume that
they are—though the majority of present-day Makonde are probably
unaware of the fact—representations of the tribal ancestress.
The references in the legend to the descent from Mahuta to the
Rovuma, and to a journey across the highlands into the Mbekuru
valley, undoubtedly indicate the previous history of the tribe, the
travels of the ancestral pair typifying the migrations of their
descendants. The descent to the neighbouring Rovuma valley, with
its extraordinary fertility and great abundance of game, is intelligible
at a glance—but the crossing of the Lukuledi depression, the ascent
to the Rondo Plateau and the descent to the Mbemkuru, also lie
within the bounds of probability, for all these districts have exactly
the same character as the extreme south. Now, however, comes a
point of especial interest for our bacteriological age. The primitive
Makonde did not enjoy their lives in the marshy river-valleys.
Disease raged among them, and many died. It was only after they
had returned to their original home near Mahuta, that the health
conditions of these people improved. We are very apt to think of the
African as a stupid person whose ignorance of nature is only equalled
by his fear of it, and who looks on all mishaps as caused by evil
spirits and malignant natural powers. It is much more correct to
assume in this case that the people very early learnt to distinguish
districts infested with malaria from those where it is absent.
This knowledge is crystallized in the
ancestral warning against settling in the
valleys and near the great waters, the
dwelling-places of disease and death. At the
same time, for security against the hostile
Mavia south of the Rovuma, it was enacted
that every settlement must be not less than a
certain distance from the southern edge of the
plateau. Such in fact is their mode of life at the
present day. It is not such a bad one, and
certainly they are both safer and more
comfortable than the Makua, the recent
intruders from the south, who have made USUAL METHOD OF
good their footing on the western edge of the CLOSING HUT-DOOR
plateau, extending over a fairly wide belt of
country. Neither Makua nor Makonde show in their dwellings
anything of the size and comeliness of the Yao houses in the plain,
especially at Masasi, Chingulungulu and Zuza’s. Jumbe Chauro, a
Makonde hamlet not far from Newala, on the road to Mahuta, is the
most important settlement of the tribe I have yet seen, and has fairly
spacious huts. But how slovenly is their construction compared with
the palatial residences of the elephant-hunters living in the plain.
The roofs are still more untidy than in the general run of huts during
the dry season, the walls show here and there the scanty beginnings
or the lamentable remains of the mud plastering, and the interior is a
veritable dog-kennel; dirt, dust and disorder everywhere. A few huts
only show any attempt at division into rooms, and this consists
merely of very roughly-made bamboo partitions. In one point alone
have I noticed any indication of progress—in the method of fastening
the door. Houses all over the south are secured in a simple but
ingenious manner. The door consists of a set of stout pieces of wood
or bamboo, tied with bark-string to two cross-pieces, and moving in
two grooves round one of the door-posts, so as to open inwards. If
the owner wishes to leave home, he takes two logs as thick as a man’s
upper arm and about a yard long. One of these is placed obliquely
against the middle of the door from the inside, so as to form an angle
of from 60° to 75° with the ground. He then places the second piece
horizontally across the first, pressing it downward with all his might.
It is kept in place by two strong posts planted in the ground a few
inches inside the door. This fastening is absolutely safe, but of course
cannot be applied to both doors at once, otherwise how could the
owner leave or enter his house? I have not yet succeeded in finding
out how the back door is fastened.