Textbook of Biochemistry With Clinical Correlations, 6th Edition

by Thomas M. Devlin (Drexel University School of Medicine, Philadelphia, Pennsylvania )

• ISBN13: 9780471678083
• ISBN10: 0471678082
• Edition: 6th
• Format: Hardcover
• Copyright: 2005-12-01
• Publisher: Wiley

Summary

Thomas M. Devlin's Textbook of Biochemistry with Clinical Correlations presents the biochemistry of mammalian cells, relates events at a cellular level to the subsequent physiological processes in the whole animal, and cites examples of human diseases derived from aberrant biochemical processes. The organization and content are tied together to provide students with the complete picture of biochemistry and how it relates to humans. Loaded with new material and chapters and brimming with detailed, full-color illustrations that clearly explain associated concepts, this sixth edition is an indispensable tool for students and professionals in the medical or health sciences.Key Features of the Sixth Edition: Over 250 Clinical Correlations highlighting the significance of the biochemistry to clinical conditions and diseases MCAT-Style Questions with annontated answers in every chapter - in a format similar to that used by the National Board of Medical Examiners More than 1,200 high-quality, full-color illustrations A concise appendix reviewing important Organic Chemistry ConceptsNew to the Sixth Edition: Fully Updated with a significant revision of all chapters and major topics Two new chapters: Fundamentals of Signal Transduction and Cell Cycle, Programmed Cell Death, and Cancer A Glossary that explains important biochemical terms New sections on the Basal Lamina Protein Complex and Molecular Motors

Author Biography

Thomas M. Devlin, Ph.D. - Professor Emeritus, Drexel University School of Medicine.

Table of Contents

Preface	xxi
Acknowledgments	xxiii
Contributors	xxv
PART I STRUCTURE OF MACROMOLECULES
Eukaryotic Cell Structure	1	(22)
Thomas M. Devlin
Overview: Cells and Cellular Compartments	2	(1)
Water, pH, and Solutes: The Aqueous Environment of Cells	3	(8)
Composition of Eukaryotic Cells: Functional Roles of Subcellular Organelles and Membrane Systems	11	(8)
Integration and Control of Cellular Functions	19	(4)
Bibliography	20	(1)
Questions and Answers	20
Clinical Correlations
Blood Bicarbonate Concentration in Metabolic Acidosis	10	(5)
Mitochondrial Diseases	15	(1)
Lysosomal Enzymes and Gout	16	(2)
Lysosomal Acid Lipase Deficiency	18	(1)
Peroxisome Biogenesis Disorders (PBD)	19	(4)
DNA and RNA: Composition and Structure	23	(52)
Stephen A. Woski
Francis J. Schmidt
Overview	24	(1)
Structural Components of Nucleic Acids: Nucleobases, Nucleosides, and Nucleotides	25	(4)
Structure of DNA	29	(17)
Higher-Order DNA Structure	46	(12)
DNA Sequence and Function	58	(4)
RNA Structure	62	(2)
Types of RNA	64	(11)
Bibliography	71	(1)
Questions and Answers	71
Clinical Correlations
DNA Vaccines	25	(14)
Diagnostic Use of DNA Arrays in Medicine and Genetics	39	(3)
Antitumor Antibiotics That Change the Shape of DNA	42	(3)
Hereditary Persistence of Fetal Hemoglobin	45	(1)
Telomerase as a Target for Anticancer Agents	46	(3)
Expansion of DNA Triple Repeats and Human Disease	49	(4)
Topoisomerases in the Treatment of Disease	53	(14)
Staphylococcal Resistance to Erythromycin	67	(8)
Proteins I: Composition and Structure	75	(58)
Richard M. Schultz
Michael N. Liebman
Functional Roles of Proteins in Humans	76	(1)
Amino Acid Composition of Proteins	77	(4)
Charge and Chemical Properties of Amino Acids and Proteins	81	(9)
Primary Structure of Proteins	90	(2)
Higher Levels of Protein Organization	92	(7)
Other Types of Proteins	99	(10)
Folding of Proteins from Randomized to Unique Structures: Protein Stability	109	(7)
Dynamic Aspects of Protein Structure	116	(1)
Characterization, Purification, and Determination of Protein Structure and Organization	117	(16)
Bibliography	129	(2)
Questions and Answers	131
Clinical Correlations
Plasma Proteins in Diagnosis of Disease	87	(4)
Differences in Insulins Used in Treatment of Diabetes Mellitus	91	(1)
A Nonconservative Mutation Occurs in Sickle Cell Anemia	92	(8)
Diseases of Collagen Synthesis	100	(5)
Hyperlipidemias	105	(2)
Hypolipoproteinemias	107	(3)
Glycosylated Hemoglobin, HbAlc	110	(1)
Proteins as Infectious Agents: Prions and Human Transmissible Spongiform Encephalopathies (TSEs)	111	(12)
Use of Amino Acid Analysis in Diagnosis of Disease	123	(10)
PART II TRANSMISSION OF INFORMATION
DNA Replication, Recombination, and Repair	133	(42)
Howard J. Edenberg
Common Features of Replication, Recombination, and Repair	134	(1)
DNA Replication	135	(18)
Recombination	153	(5)
Repair	158	(17)
Bibliography	171	(1)
Questions and Answers	171
Clinical Correlations
Chemotherapy Can Target Precursors of DNA Synthesis	136	(10)
Topoisomerases as Drug Targets	146	(4)
Cancer and the Cell Cycle	150	(1)
Nucleoside Analogs and Drug Resistance in HIV Therapy	151	(7)
Gene Therapy	158	(2)
Chemotherapy, DNA Damage, and Repair	160	(1)
Nucleoside Analogs as Drugs: Thiopurines	161	(1)
Individualized Medicine	161	(3)
Xeroderma Pigmentosum	164	(2)
Mismatch Repair and Cancer	166	(9)
RNA: Transcription and RNA Processing	175	(26)
Francis J. Schmidt
David R. Setzer
Overview	176	(1)
Mechanisms of Transcription	176	(6)
Transcription in Eukaryotes	182	(6)
RNA Processing	188	(7)
RNA Export and Quality Control	195	(1)
Small Inhibitory RNAs	196	(1)
Transcription-Coupled DNA Repair	196	(1)
Nucleases and RNA Turnover	197	(4)
Bibliography	198	(1)
Questions and Answers	199
Clinical Correlations
Antibiotics and Toxins That Target RNA Polymerase	179	(4)
Fragile X Syndrome: An RNA-Chromatin Disease?	183	(2)
Involvement of Transcriptional Factors in Carcinogenesis	185	(7)
Thalassemia Due to Defects in Messenger RNA Synthesis	192	(1)
Autoimmunity in Connective Tissue Disease	193	(4)
Cockayne Syndrome	197	(4)
Protein Synthesis: Translation and Posttranslational Modifications	201	(44)
Dohn Glitz
Overview	202	(1)
Components of the Translational Apparatus	202	(11)
Protein Biosynthesis	213	(9)
Protein Maturation: Folding, Modification, Secretion, and Targeting	222	(5)
Membrane and Organelle Targeting	227	(4)
Further Posttranslational Modifications	231	(5)
Regulation of Translation	236	(3)
Protein Degradation and Turnover	239	(6)
Bibliography	240	(2)
Questions and Answers	242
Clinical Correlations
Missense Mutations: Hemoglobin	206	(1)
Mutation to Form a Terminator Codon	206	(1)
α-Thalassemia	207	(1)
Programmed Frameshifting in Biosynthesis of HIV Proteins	208	(13)
Mutation in Mitochondrial Ribosomal RNA Results in Antibiotic-Induced Deafness	221	(2)
Deletion of a Codon, Incorrect Posttranslational Modification, and Premature Protein Degradation: Cystic Fibrosis	223	(1)
Protein Misfolding and Aggregation: Creutzfeldt--Jacob Disease, Mad Cow Disease, Alzheimer's Disease, and Huntington's Disease	224	(6)
Diseases of Lysosome Function	230	(3)
Familial Hyperproinsulinemia	233	(1)
Absence of Posttranslational Modification: Multiple Sulfatase Deficiency	234	(3)
Defects in Collagen Synthesis	237	(8)
Recombinant DNA and Biotechnology	245	(46)
Gerald Soslau
Overview	246	(1)
The Polymerase Chain Reaction	247	(1)
Restriction Endonuclease and Restriction Maps	248	(1)
DNA Sequencing	249	(2)
Recombinant DNA and Cloning	251	(3)
Selection of Specific Cloned DNA in Libraries	254	(4)
Detection and Identification of Nucleic Acids and DNA-Binding Proteins	258	(5)
Complementary DNA and Complementary DNA Libraries	263	(3)
Bacteriophage, Cosmid, and Yeast Cloning Vectors	266	(2)
Analysis of Long Stretches of DNA	268	(1)
Expression Vectors and Fusion Proteins	269	(2)
Expression Vectors in Eukaryotic Cells	271	(1)
Site-Directed Mutagenesis	272	(5)
Applications of Recombinant DNA Technologies	277	(5)
Genomics, Proteomics, and Microarray Analysis	282	(9)
Bibliography	287	(1)
Questions and Answers	287
Clinical Correlations
Polymerase Chain Reaction	248	(1)
Restriction Mapping and Evolution	249	(2)
Direct Sequencing of DNA for the Diagnosis of Genetic Disorders	251	(3)
Multiplex PCR Analysis of the HGPTase Gene Defects in the Lesch--Nyhan Syndrome	254	(6)
Restriction Fragment Length Polymorphisms Determine the Clonal Origin of Tumors	260	(1)
Single-Strand Conformational Polymorphism for Detection of Spontaneous Mutations That May Lead to Sids	261	(14)
Site-Directed Mutagenesis of HSV IgD	275	(3)
RNA-Mediated Inhibition of HIV	278	(1)
Gene Therapy: Normal Genes Can Be Introduced Into Cells with Defective Genes	279	(1)
Transgenic Animal Models	280	(1)
Knockout Mice to Define a Role for the P2Y1 Purinoceptor	281	(2)
Microarray Analysis of Breast Cancer	283	(8)
Regulation of Gene Expression	291	(28)
Daniel L. Weeks
John E. Donelson
Overview	292	(1)
Unit of Transcription in Bacteria: The Operon	292	(1)
Lactose Operon of E. Coli	293	(4)
Tryptophan Operon of E. Coli	297	(5)
Other Bacterial Operons	302	(2)
Bacterial Transposons	304	(1)
Gene Expression in Eukaryotes	305	(2)
Preinitiation Complex in Eukaryotes: Transcription Factors, RNA Polymerase II, and DNA	307	(5)
Regulation of Eukaryotic Gene Expression	312	(7)
Bibliography	316	(1)
Questions and Answers	317
Clinical Correlations
Transmissible Multiple Drug Resistance	305	(2)
Rubinstein--Taybi Syndrome	307	(7)
Tamoxifen and Targeting of Estrogen Receptor	314	(1)
Transcription Factors and Cardiovascular Disease	314	(5)
PART III FUNCTIONS OF PROTEINS
Proteins II: Structure-Function Relationships in Protein Families	319	(46)
Richard M. Schultz
Overview	320	(1)
Antibody Molecules: Immunoglobulin Superfamily of Proteins	320	(8)
Proteins with a Common Catalytic Mechanism: Serine Proteases	328	(10)
Hemoglobin and Myoglobin	338	(14)
The Basal Lamina Protein Complex	352	(13)
Bibliography	360	(1)
Questions and Answers	361
Clinical Correlations
The Complement Proteins	323	(1)
Functions of Different Antibody Classes	323	(1)
Immunization	324	(6)
Fibrin Formation in a Myocardial Infarct and Use of Recombinant Tissue Plasminogen Activator (rt-PA)	330	(1)
Involvement of Serine Proteases in Tumor Cell Metastasis	330	(9)
Hemoglobinopathies	339	(26)
Enzymes: Classification, Kinetics, and Control	365	(48)
Henry Weiner
Overview	366	(1)
Classifications of Enzymes	367	(4)
General Concepts of Enzyme Mechanisms	371	(4)
Active Site of an Enzyme	375	(3)
Coenzymes, Co-Substrates, and Cofactors	378	(6)
Kinetics of Chemical Reactions	384	(2)
Enzyme Kinetics of One-Substrate Reactions	386	(8)
Kinetics of Two-Substrate Reactions	394	(1)
Inhibitors	395	(6)
Regulation of Enzyme Activity	401	(3)
Regulation of Metabolic Pathways	404	(1)
Clinical Applications of Enzymes	405	(8)
Bibliography	410	(1)
Questions and Answers	410
Clinical Correlations
Mutation of a Coenzyme-Binding Site Results in Clinical Disease	378	(11)
A Case of Gout Demonstrates Two Phases in the Mechanism of Enzyme Action	389	(1)
Physiological Effect of Changes in Enzyme Km Values	390	(3)
Thermal Lability of Glucose 6-Phosphate Dehydrogenase Results in Hemolytic Anemia	393	(1)
Alcohol Dehydrogenase Isoenzymes with Different pH Optima	394	(2)
Inhibitors of Xanthine Oxidase Isolated from Plants	396	(1)
Design of a Selective Inhibitor	397	(3)
A Case of Poisoning	400	(1)
Mushrooms and Alcohol Metabolism	400	(1)
A Case of Gout Demonstrates the Difference Between an Allosteric and Substrate-Binding Site	401	(6)
Identification and Treatment of an Enzyme Deficiency	407	(1)
Ambiguity in the Assay of Mutated Enzymes	407	(6)
The Cytochromes P450 and Nitric Oxide Synthases	413	(30)
Linda J. Roman
Bettie Sue Siler Masters
Overview	414	(1)
Cytochromes P450: Properties and Function	414	(1)
Cytochrome P450 Reaction Cycle	415	(1)
Cytochrome P450 Electron Transport Systems	416	(2)
Cytochrome P450: Nomenclature and Isoforms	418	(1)
Cytochrome P450: Substrates and Physiological Functions	419	(1)
Cytochromes P450 Participate in the Synthesis of Steroid Hormones and Oxygenation of Endogenous Compounds	420	(8)
Cytochrome P450 Induction and Inhibition	428	(4)
The Nitric Oxide Synthases: Properties and Function	432	(1)
Nitric Oxide Synthase Isoforms and Physiological Functions	433	(10)
Bibliography	439	(1)
Questions and Answers	440
Clinical Correlations
Congenital Adrenal Hyperplasia: Deficiency of CYP21A2	423	(1)
Steroid Hormone Production During Pregnancy	423	(3)
Cytochrome P450 Inhibition: Drug--Drug Interactions and Adverse Effects	426	(2)
Role of CYP2E1 in Acetaminophen-Induced Liver Toxicity	428	(1)
Cytochrome P450 Induction: Drug--Drug Interactions and Adverse Effects	429	(2)
Genetic Polymorphisms of P450 Enzymes	431	(5)
Mechanism of Action of Sildenafil	436	(1)
Clinical Aspects of Nitric Oxide Production	437	(1)
History of Nitroglycerin	438	(5)
Biological Membranes: Structure and Membrane Transport	443	(46)
Thomas M. Devlin
Overview	444	(1)
Chemical Composition of Membranes	444	(6)
Micelles, Lipid Bilayers, and Liposomes	450	(3)
Structure of Biological Membranes	453	(8)
Movement of Molecules Through Membranes	461	(3)
Membrane Channels	464	(8)
Membrane Transporters	472	(2)
Passive Transport	474	(1)
Active Transport	475	(8)
Ionophores	483	(6)
Bibliography	485	(1)
Questions and Answers	485
Clinical Correlations
Liposomes as Carriers of Drugs and Enzymes	452	(7)
Abnormalities of Cell Membrane Fluidity in Disease	459	(7)
Cystic Fibrosis and the Cl-Channel	466	(2)
The Mammalian Kidney and Aquaporins	468	(13)
Diseases Involving the Superfamily of ABC Transporters	481	(2)
Diseases Due to Loss of Membrane Transport Systems	483	(6)
Fundamentals of Signal Transduction	489	(40)
George R. Dubyak
Overview	490	(1)
Intercellular Signal Transduction	491	(2)
Receptors for Secreted Molecules	493	(1)
Intracellular Signal Transduction by Cell-Surface Receptors	494	(6)
Ligand-Gated Ion Channel Receptors	500	(3)
Enzyme-Linked Receptors	503	(4)
Cytokine Receptors	507	(2)
G-Protein-Coupled Receptors	509	(6)
Cyclic-AMP-Based Signal Transduction	515	(3)
Cyclic-GMP-Based Signal Transduction	518	(1)
Calcium-Based Signal Transduction	519	(3)
Phospholipid-Based Signal Transduction	522	(2)
Integration of Signal Transduction Pathways Into Signal Transduction Networks	524	(5)
Bibliography	525	(1)
Questions and Answers	526
Clinical Correlations
ErbB/HER-Family Receptor Tyrosine Kinases as Targets for Cancer Chemotherapy	505	(5)
G-Protein-Coupled Chemokine Receptors as Targets for the Human Immunodeficiency Virus (HIV)	510	(2)
Gsα G-Protein Mutations in Pituitary Gland Tumors and Endocrine Diseases	512	(3)
Alterations in β-Adrenergic Receptor Signaling Proteins in Congestive Heart Failure	515	(4)
Nitric Oxide/cGMP Signaling Axis as Therapeutic Targets in Cardiac and Vascular Disorders	519	(10)
PART IV METABOLIC PATHWAYS AND THEIR CONTROL
Bioenergetics and Oxidative Metabolism	529	(52)
Diana S. Beattie
Energy-Producing and Energy-Utilizing Systems	530	(2)
Thermodynamic Relationships and Energy-Rich Components	532	(6)
Sources and Fates of Acetyl Coenzyme A	538	(5)
The Tricarboxylic Acid Cycle	543	(7)
Structure and Compartmentation by Mitochondrial Membranes	550	(2)
Electron Transport Chain	552	(10)
Oxidative Phosphorylation	562	(6)
Mitochondrial Inner Membrane Contains Substrate Transport Systems	568	(5)
Mitochondrial Genes and Diseases	573	(1)
Reactive Oxygen Species (ROS)	574	(7)
Bibliography	578	(1)
Questions and Answers	579
Clinical Correlations
Pyruvate Dehydrogenase Deficiency	543	(3)
Fumarase Deficiency	546	(16)
Cyanide Poisoning	562	(12)
Leber's Hereditary Optic Neuropathy	574	(1)
Mitochondrial Myopathies from Mutations in tRNA Genes	575	(1)
Exercise Intolerance in Patients with Mutations in Cytochrome b	575	(2)
Ischemia/Reperfusion Injury	577	(4)
Carbohydrate Metabolism I: Major Metabolic Pathways and Their Control	581	(56)
Robert A. Harris
Overview	582	(1)
Glycolysis	583	(4)
Glycolysis Pathway	587	(8)
Regulation of Glycolysis	595	(13)
Glyconeogenesis	608	(10)
Glycogenolysis and Glycogenesis	618	(19)
Bibliography	633	(1)
Questions and Answers	634
Clinical Correlations
Alcohol and Barbiturates	594	(1)
Arsenic Poisoning	595	(2)
Fructose Intolerance	597	(2)
Diabetes Mellitus	599	(2)
Lactic Acidosis	601	(1)
Pickled Pigs and Malignant Hyperthermia	602	(1)
Angina Pectoris and Myocardial Infarction	603	(5)
Pyruvate Kinase Deficiency and Hemolytic Anemia	608	(1)
Hypoglycemia and Premature Infants	609	(9)
Hypoglycemia and Alcohol Intoxication	618	(3)
Glycogen Storage Diseases	621	(16)
Carbohydrate Metabolism II: Special Pathways and Glycoconjugates	637	(24)
Nancy B. Schwartz
Overview	638	(1)
Pentose Phosphate Pathway	638	(5)
Sugar Interconversions and Nucleotide-Linked Sugar Formation	643	(5)
Biosynthesis of Complex Polysaccharides	648	(1)
Glycoproteins	649	(3)
Proteoglycans	652	(9)
Bibliography	658	(1)
Questions and Answers	658
Clinical Correlations
Glucose 6-Phosphate Dehydrogenase: Genetic Deficiency or Variants in Erythrocytes	640	(1)
Wernicke--Korsakoff Syndrome: Deficiency or Genetic Variants of Transketolase	641	(3)
Carbohydrate-Deficient Glycoprotein Syndromes (CDGS)	644	(1)
Essential Fructosuria and Fructose Intolerance: Deficiency of Fructokinase and Fructose 1-phosphate Aldolase	644	(1)
Galactosemia: Inability to Transform Galactose into Glucose	645	(1)
Pentosuria: Deficiency of Xylitol Dehydrogenase	646	(1)
Glucuronic Acid: Physiological Significance of Glucuronide Formation	647	(2)
Blood Group Substances	649	(3)
Common Carbohydrate Marker of Lysosomal Targeting and I-Cell Disease	652	(1)
Aspartylglycosylaminuria: Absence of 4-L-Aspartylglycosamine Amidohydrolase	653	(1)
Glycolipid Disorders	654	(1)
Heparin is an Anticoagulant	655	(1)
Chondrodystrophies Due to Sulfation Defects	655	(2)
Mucopolysaccharidoses	657	(4)
Lipid Metabolism I: Synthesis, Storage, and Utilization of Fatty Acids and Triacylglycerols	661	(34)
Martin D. Snider
J. Denis McGarry
Richard W. Hanson
Overview	662	(1)
Chemical Nature of Fatty Acids and Acylglycerols	663	(2)
Interorgan Transport of Fatty Acids and Their Primary Products	665	(3)
Synthesis of Fatty Acids: Lipogenesis	668	(8)
Storage of Fatty Acids as Triacylglycerol	676	(4)
Utilization of Fatty Acids for Energy Production	680	(10)
Regulation of Lipid Metabolism	690	(5)
Bibliography	692	(1)
Questions and Answers	693
Clinical Correlations
Obesity	665	(1)
Role of Fatty Acid Metabolism in Type 2 Diabetes	666	(13)
Triacylglycerol/Fatty Acid Cycle	679	(3)
Genetic Deficiencies in Carnitine Transport or Carnitine Palmitoyltransferase	682	(2)
Genetic Deficiencies in the Acyl-CoA Dehydrogenases	684	(2)
Refsum's Disease	686	(3)
Ketone Bodies as a Fuel: The Atkins Diet	689	(6)
Lipid Metabolism II: Pathways of Metabolism of Special Lipids	695	(48)
Robert H. Glew
Overview	696	(1)
Phospholipids	696	(11)
Cholesterol	707	(13)
Sphingolipids	720	(10)
Prostaglandins and Thromboxanes	730	(4)
Lipoxygenase and Oxyeicosatetraenoic Acids	734	(9)
Bibliography	738	(1)
Questions and Answers	739
Clinical Correlations
Respiratory Distress Syndrome	699	(18)
Treatment of Hypercholesterolemia	717	(1)
Atherosclerosis	717	(12)
Diagnosis of Gaucher's Disease in an Adult	729	(14)
Amino Acid Metabolism	743	(46)
Marguerite W. Coomes
Overview	744	(1)
Incorporation of Nitrogen into Amino Acids	745	(5)
Transport of Nitrogen to Liver and Kidney	750	(1)
Urea Cycle	751	(3)
Synthesis and Degradation of Individual Amino Acids	754	(35)
Bibliography	784	(1)
Questions and Answers	785
Clinical Correlations
Carbamoyl Phosphate Synthetase and N-Acetylglutamate Synthetase Deficiencies	754	(1)
Deficiency of Urea Cycle Enzymes	755	(1)
Diseases of Proline Metabolism	756	(3)
Selenoproteins	759	(1)
Nonketotic Hyperglycinemia	760	(2)
Folic Acid Deficiency	762	(2)
Phenylketonuria	764	(2)
Disorders of Tyrosine Metabolism	766	(1)
Parkinson's Disease	766	(4)
Hyperhomocysteinemia and Atherogenesis	770	(1)
Diseases of Sulfur Amino Acids	770	(3)
Glutaric Aciduria	773	(2)
Schizophrenia and Other Tryptophan-Derived Neurotransmitter-Associated Diseases	775	(2)
Diseases of Metabolism of Branched-Chain Amino Acids	777	(3)
Diseases of Propionate and Methylmalonate Metabolism	780	(1)
Diseases Involving Lysine and Ornithine	780	(1)
Histidinemia	781	(1)
Diseases of Folate Metabolism	782	(7)
Purine and Pyrimidine Nucleotide Metabolism	789	(34)
Joseph G. Cory
Overview	790	(1)
Metabolic Functions of Nucleotide	790	(1)
Metabolism of Purine Nucleotides	791	(11)
Metabolism of Pyrimidine Nucleotides	802	(4)
Deoxyribonucleotide Formation	806	(2)
Nucleoside and Nucleotide Kinases	808	(2)
Nucleotide Metabolizing Enzymes as a Function of the Cell Cycle and Rate of Cell Division	810	(1)
Nucleotide Coenzyme Synthesis	811	(2)
Synthesis and Utilization of 5-Phosphoribosyl-1-Pyrophosphate	813	(1)
Chemotherapeutic Agents That Interfere with Purine and Pyrimidine Nucleotide Metabolism	814	(9)
Bibliography	819	(1)
Questions and Answers	820
Clinical Correlations
Gout	796	(2)
Lesch--Nyhan Syndrome	798	(2)
Increased Cytosolic 5'-Nucleotidase Activity	800	(1)
Immunodeficiency Diseases Associated with Defects in Purine Nucleoside Degradation	801	(1)
Patients Undergoing Cancer Treatment	802	(1)
Subclass of Patients with Autism	803	(1)
Hereditary Orotic Aciduria	804	(19)
Iron and Heme Metabolism	823	(26)
William M. Awad, Jr.
Iron Metabolism: Overview	824	(1)
Iron-Containing Proteins	824	(2)
Intestinal Absorption of Iron	826	(2)
Molecular Regulation of Iron Utilization	828	(2)
Iron Distribution and Kinetics	830	(3)
Heme Biosynthesis	833	(7)
Heme Catabolism	840	(9)
Bibliography	845	(1)
Questions and Answers	845
Clinical Correlations
Iron Overload and Infection	825	(1)
Microbial Pathogenicity and Iron	825	(2)
Iron--Sulfur Cluster Synthesis and Human Disease	827	(1)
Friedreich's Ataxia	827	(1)
Duodenal Iron Absorption	828	(2)
Mutant Iron-Responsive Elements	830	(1)
Ceruloplasmin Deficiency	831	(1)
Iron-Deficiency Anemia	832	(1)
Hemochromatosis Type I: Molecular Genetics and the Issue of Iron-Fortified Diets	832	(1)
Hemochromatosis Type III	833	(3)
Acute Intermittent Porphyria	836	(5)
Cytoprotective Role of Heme Oxygenase	841	(2)
Neonatal Isoimmune Hemolysis	843	(1)
Bilirubin UDP-Glucuronosyltransferase Deficiency	843	(1)
Elevation of Serum Conjugated Bilirubin	844	(5)
Metabolic Interrelationships	849	(42)
Robert A. Harris
David W. Crabb
Overview	850	(1)
Starve-Feed Cycle	850	(13)
Mechanisms Involved in Switching Liver Metabolism Between the Well-Fed and Starved States	863	(10)
Interrelationship of Tissues in Nutritional and Hormonal States	873	(18)
Bibliography	887	(2)
Questions and Answers	889
Clinical Correlations
Obesity	851	(1)
Protein Malnutrition	852	(1)
Starvation	852	(5)
Reye's Syndrome	857	(4)
Hyperglycemic, Hyperosmolar Coma	861	(1)
Hyperglycemia and Protein Glycation	861	(15)
Diabetes Mellitus, Type 2	876	(1)
Diabetes Mellitus, Type 1	877	(1)
Polyol Pathway and Complications of Diabetes	878	(1)
Cancer Cachexia	879	(12)
PART V PHYSIOLOGICAL PROCESSES
Biochemistry of Hormones	891	(58)
Thomas J. Schmidt
Gerald Litwack
Overview	892	(1)
Hormones and the Hormonal Cascade System	893	(7)
Synthesis of Polypeptide and Amino Acid-Derived Hormones	900	(6)
Protein Hormone Signaling	906	(8)
Membrane Hormone Receptors	914	(3)
Intracellular Hormone Cascade: Protein Kinases	917	(8)
Steroid Hormones	925	(13)
Steroid Hormone Receptors	938	(11)
Bibliography	945	(1)
Questions and Answers	946
Clinical Correlations
Testing Activity of the Anterior Pituitary	896	(5)
Hypopituitarism	901	(19)
Decreased Insulin Receptor Kinase Activity in Gestational Diabetes Mellitus	920	(17)
Oral Contraception	937	(3)
Apparent Mineralocorticoid Excess Syndrome	940	(3)
Mineralocorticoid Receptor Mutation Results in Hypertension and Toxemia of Pregnancy	943	(6)
Molecular Cell Biology	949	(64)
Thomas E. Smith
Overview	950	(1)
Nervous Tissue: Metabolism and Function	950	(11)
The Eye: Metabolism and Vision	961	(15)
Molecular Motors and Associated Proteins	976	(15)
Mechanism of Blood Coagulation	991	(22)
Bibliography	1008	(2)
Questions and Answers	1010
Clinical Correlations
Lambert--Eaton Myasthenic Syndrome	957	(1)
Myasthenia Gravis: A Neuromuscular Disorder	958	(7)
Macula Degeneration and Loss of Vision	965	(1)
Niemann--Pick Disease and Retinitis Pigmentosa	966	(1)
Retinitis Pigmentosa from a Mutation in the Gene for Peripherin	967	(6)
Leber Congenital Amaurosis: Retinal Dystrophy Leading to Blindness	973	(7)
Glycation and Myosin Structure and Function	980	(1)
Familial Hypertropic Cardiomyopathies and Mutations in Muscle Proteins	981	(1)
Dilated Cardiomyopathy and Mutations in Actin	982	(3)
Troponin Subunits as Markers for Myocardial Infarction	985	(1)
Voltage-Gated Ion Channelopathies	986	(1)
Ion Channels and Cardiac Muscle Disease	986	(3)
Mutations Affecting Pigmentation: Is There a Molecular Motor Connection?	989	(5)
Intrinsic Pathway Defects: Prekallikrein Deficiency	994	(5)
Classic Hemophilia	999	(1)
Use of Recombinant Factor Vlla to Control Bleeding	999	(5)
Thrombosis: Defects of the Protein C Pathway and Increased Levels of Coagulation Factors	1004	(9)
Cell Cycle, Programmed Cell Death, and Cancer	1013	(24)
Richard M. Schultz
Overview	1014	(1)
Cell Cycle	1014	(6)
Apoptosis: Programmed Cell Death	1020	(4)
Cancer	1024	(13)
Bibliography	1032	(1)
Questions and Answers	1033
Clinical Correlations
Oncogenic DNA Viruses	1025	(4)
Molecularly Targeted Anticancer Drug	1029	(1)
Environmental Cause of Human Cancers	1030	(7)
Digestion and Absorption of Basic Nutritional Constituents	1037	(34)
Ulrich Hopfer
Overview	1038	(1)
General Considerations	1039	(5)
Epithelial Transport	1044	(8)
Digestion and Absorption of Proteins	1052	(4)
Digestion and Absorption of Carbohydrates	1056	(3)
Digestion and Absorption of Lipids	1059	(6)
Bile Acid Metabolism	1065	(6)
Bibliography	1067	(1)
Questions and Answers	1068
Clinical Correlations
Familial Chloridorrhea Causes Metabolic Alkalosis	1046	(3)
Cystic Fibrosis	1049	(1)
Bacterial Toxigenic Diarrheas and Electrolyte Replacement Therapy	1049	(5)
Neutral Amino Aciduria: Hartnup Disease	1054	(4)
Disaccharidase Deficiency	1058	(3)
Pharmacological Interventions to Prevent Fat Absorption and Obesity	1061	(3)
Cholesterol Stones	1064	(1)
A-β-Lipoproteinemia	1065	(6)
Principles of Nutrition I: Macronutrients	1071	(20)
Stephen G. Chaney
Overview	1072	(1)
Energy Metabolism	1072	(1)
Protein Metabolism	1073	(3)
Protein--Energy Malnutrition	1076	(1)
Excess Protein--Energy Intake	1077	(2)
Carbohydrates	1079	(1)
Fats	1079	(1)
Fiber	1080	(2)
Composition of Macronutrients in the Diet	1082	(9)
Bibliography	1086	(2)
Questions and Answers	1088
Clinical Correlations
Vegetarian Diets and Protein--Energy Requirements for Children	1075	(1)
Dietary Protein Intake and Renal Disease	1076	(1)
Providing Adequate Protein and Calories for Hospitalized Patients	1077	(3)
Carbohydrate Loading and Athletic Endurance	1080	(1)
High-Carbohydrate Versus High-Fat Diet for Diabetics	1081	(2)
Polyunsaturated Fatty Acids and Risk Factors for Heart Disease	1083	(3)
Metabolic Adaptation: Relationship Between Carbohydrate Intake and Serum Triacylglycerols	1086	(5)
Principles of Nutrition II: Micronutrients	1091	(30)
Stephen G. Chaney
Overview	1092	(1)
Assessment of Malnutrition	1092	(1)
Dietary Reference Intakes	1093	(1)
Fat-Soluble Vitamins	1093	(9)
Water-Soluble Vitamins	1102	(1)
Energy-Releasing Water-Soluble Vitamins	1102	(5)
Hematopoietic Water-Soluble Vitamins	1107	(3)
Other Water-Soluble Vitamins	1110	(2)
Macrominerals	1112	(1)
Trace Minerals	1113	(2)
The American Diet: Fact and Fallacy	1115	(1)
Assessment of Nutritional Status in Clinical Practice	1116	(5)
Bibliography	1117	(2)
Questions and Answers	1119
Clinical Correlations
Nutritional Considerations in Cystic Fibrosis	1096	(1)
Renal Osteodystrophy	1097	(4)
Nutritional Considerations in Newborn Infants	1101	(1)
Anticonvulsant Drugs and Vitamin Requirements	1101	(2)
Nutritional Considerations in Alcoholics	1103	(3)
Vitamin B6 Requirements and Oral Contraceptives	1106	(2)
Gene Polymorphisms and Folic Acid Requirement	1108	(5)
Diet and Osteoporosis	1113	(4)
Nutritional Needs of Elderly Persons	1117	(4)
Appendix Review of Organic Chemistry	1121	(12)
Carol N. Angstadt
Glossary	1133	(24)
Francis Vella
Index	1157