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Written for a broad, cross-disciplinary audience, the Encyclopedia of Biological Chemistry addresses the fundamental discipline of biological chemistry underlying virtually all of the life sciences. This compilation of more than 500 different entries encompasses all aspects of biochemistry, as well as the extensions of this subject into the related fields of molecular biology, cell biology, genetics and biophysics. This comprehensive encyclopedia covers all areas of biological chemistry written by more than 500 selected international experts. Articles are generously illustrated including more than 800 images in four-color. Each entry contains a clear, concise review of the topic along with illustrations, a glossary of technical terms and a section for additional reading. Each entry further contains general background and term definitions as well as a comprehensive review of the current research in the field. Students, science journalists and scientists seeking a concise introduction to specific topics will appreciate the clear, tabular format of each entry. Also available online via ScienceDirect – featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com. • Four-volume set with topics arranged from A to Z for easy reference • Seven subject areas covering all areas of biological chemistry • Over 500 full-color articles of 4-9 pages each • Over 1300 illustrations throughout with 800 in 4-color and over 200 tables • Glossary of specialized terms and 'Further Reading' section provided for every article • Includes entries on the latest research techniques • Appropriate for students, researchers, and professionals Audience: Upper level college students, postdocs, and professionals in biochemistry, biophysics, cell biology, molecular biology, neuroscience, pharmacology, and oncology, academic and industrial libraries, and pharmaceutical companies. Cover Page 843 Editors-in-Chief 777 Associate Editors 779 Preface 782 Notes on the Subject Index 783 Content by Volume 784 Volume 1 784 Volume 2 792 Volume 3 800 Volume 4 808 Content by Subject 813 Lipids, Carbohydrates, Membranes and Membrane Proteins 813 Metabolism, Vitamins and Hormones 815 Cell Architecture and Function 817 Protein/Enzyme Structure Function and Degradation 820 Bioenergetics 823 Molecular Biology 829 Signaling 835 Techniques and Methodology 842 Volume 1 (A-D) -1 Volume 2 (E-M) 1 Volume 3 (N-R) -1 Volume 4 (S-Z) -1 EF-G and EF-Tu Structures and Translation Elongation in Bacteria 1 Elongation 1 Elongation Factor EF-Tu 1 Elongation Factor EF-G 3 The Ternary Complex of EF-Tu 3 The Structural Similarity of EF-G and the Ternary Complex 4 Action of Elongation Factors on the Ribosome 4 Antibiotic Action on EF-Tu 4 See Also The Following Articles 5 Glossary 5 Further Reading 5 Eicosanoid Receptors 6 Eicosanoid Biosynthesis Pathways 6 The Lipoxygenase (LO) Pathway 6 The Cyclooxygenase (COX) Pathway 6 The Epoxygenase Pathway 6 Eicosanoid Action 6 Receptors of Lipoxygenase Metabolites 7 Leukotriene Receptors 7 Lipoxin Receptors 7 The 5-Oxo-ETE Receptor 7 Prostaglandin (PG) Receptors 7 PPARs 8 See Also the Following Articles 8 Glossary 8 Further Reading 9 Elastin 10 Composition and Primary Sequence 10 Amino Acid Composition 10 Amino Acid Sequence 10 Isolation of Elastin 10 Insoluble Elastin 10 Soluble Elastin 10 The Elastin Gene 11 Gene Structure 11 Gene Promoter 11 Elastin Gene Expression 11 Elastin mRNAs 11 Elastin Protein Isoforms 11 Regulation of Elastin Gene Expression 11 Transcriptional Regulation 11 Posttranscriptional Regulation 11 See Alsothe Following Articles 12 Glossary 12 Further Reading 12 Endocannabinoids 13 Synthesis 13 Anandamide 13 2-Arachidonoylglycerol 13 Physiological Regulation of Endocannabinoid Synthesis 13 Anandamide 13 2-Arachidonoylglycerol 13 Deactivation 13 Transport into Cells 14 Intracellular Hydrolysis 14 Cannabinoid Receptors 14 Functions 15 See Also The Following Articles 15 Glossary 15 Further Reading 15 Endocytosis 16 Clathrin-Mediated Endocytosis 16 Adaptor Proteins 16 Dynamin 16 Clathrin-Independent Endocytosis 17 Caveolae 18 Noncoated Endocytosis and Macropinocytosis 18 Phagocytosis 18 Fate of Internalized Membrane and Content 18 See Also the Following Articles 19 Glossary 19 Further Reading 19 Endoplasmic Reticulum-Associated Protein Degradation 20 Protein Synthesis and Folding in the ER 20 Diseases Related to Failure of Protein Folding and Quality Control in the ER 21 Degradation of Aberrant Proteins Expressed in the ER: The Mannose Timer 21 Distinct ER Chaperone Networks are Involved in the GERAD Process 21 A Role for a Mannose-Binding Lectin in GERAD 22 See Also the Following Articles 22 Glossary 23 Further Reading 23 Energy Transduction in Anaerobic Prokaryotes 24 ADP Phosphorylation Driven by Chemical Coupling or by the Membrane Potential 24 Fermentation 24 Electron Transport Phosphorylation in Anaerobic Respiration 26 Decarboxylation of Dicarboxylic Acids 28 Generation of a H+-Potential by Transport of Charged Substrate and Product Molecules 29 Anoxygenic Photosynthetic Prokaryotes 29 See Also the Following Articles 30 Glossary 30 Further Reading 30 Enzyme Inhibitors 31 Reversible Catalytic-Site Inhibitors 31 Reactant and Product Analogues 31 Bisubstrate Mimics 31 Transition-State Analogues 31 Noncatalytic Site Inhibitors 34 Prevent Catalytic-Site Binding 35 Prevent Subunit Formation 35 Prevent Conformational Change for Catalysis 35 Mechanism-Based Inhibitors 35 Polyamine Synthesis 35 Other Mechanism-Based Inhibitors 36 Conclusion 36 See Also the Following Articles 37 Glossary 37 Further Reading 37 Enzyme Kinetics 38 Unireactant Enzymes and the Michaelis-Menten Equation 38 The Rapid Equilibrium Assumption 38 The Steady- State Assumption 39 A More Realistic Unireactant Reaction Sequence 39 Reversible Reactions 40 The Velocity Curve and its Linear Forms 40 Multireactant Enzymes 41 Common Mechanisms 41 Velocity Equations for Some Bireactant Mechanisms 41 Cleland’s Slope and Intercept Rules 44 See Also The Following Articles 44 Glossary 44 Further Reading 44 Enzyme Reaction Mechanisms: Stereochemistry 45 Explanation of Stereochemical Terms 45 Stereoselectivity, Stereospecificity, and Stereochemical Course of Enzymatic Reactions 45 Pioneering Study: Alcohol Dehydrogenase (ADH) 47 Analysis of Steric Course to Probe an Enzymatic Reaction Pathway 47 Stereoselectivity Can Probe Metal-Nucleotide or Enzyme-Substrate Interactions at the Transition State 48 See Also the Following Articles 49 Glossary 49 Further Reading 49 Epidermal Growth Factor Receptor Family 51 Receptors and Ligands 51 The Structure of ErbB Receptors 51 ErbB Receptor Substrates 52 Receptor-Mediated Endocytosis 53 Targeting ErbB Receptors in Cancer Therapy 54 Conservation of ErbB Receptor Signaling during Evolution 54 See Alsothe Following Articles 54 Glossary 54 Further Reading 54 ER/SR Calcium Pump: Function 56 ATP Use for Ca2+ Transport 56 Steady-State Behavior 56 The Partial Reactions of the Catalytic and Transport Cycles 56 The Coupling Mechanism 58 Free-Energy Use 58 Ca2+ Binding and Catalytic Activation 58 Nucleotide Binding and Substrate-Induced Conformational Fit 59 Phosphoryl Transfer and Hydrolytic Cleavage 59 Interconversion of Phosphorylation and Ca2+-Binding Potentials 59 Physiological Regulation and Experimental Inhibitors 59 See Also the Following Articles 60 Glossary 60 Further Reading 60 ER/SR Calcium Pump: Structure 61 Overall Description of the Structure 61 Organization of the Transmembrane Domain 61 Transmembrane Helices 61 Details of the Ca2+-Binding Sites 61 Organization of the Cytoplasmic Domain 63 Structure of the P-Domain 63 Structure of the N-Domain 63 Structure of the A-Domain 63 Structural Changes Accompanying the Dissociation of Ca2+ 63 Rearrangement of the Transmembrane Helices 63 Ca2+-Binding Sites in the E2(TG) State 64 Role of the Large Conformational Movements 64 See Also the Following Articles 65 Glossary 65 Further Reading 65 Exonucleases, Bacterial 66 Introduction 66 Biochemical Properties of Exonucleases 66 Mechanism 66 Specificity 68 Processivity 68 Structural Families 69 DEDD/DNAQ 69 DHH/RecJ 69 XthA 69 FEN-1/5 Nucleases 69 Mre11/SbcD 70 Biological Roles of RNA Exonucleases 70 Turnover 70 Processing 70 Biological Roles of DNA Exonucleases 70 Replication Fidelity 70 Recombination and DNA Repair 71 Conclusions 71 See Also the Following Articles 71 Glossary 71 Further Reading 71 F1-F0 ATP Synthase 73 Structure of the ATP Synthase Complex 73 Subunit Composition 73 F1 75 F0 75 ATP Synthesis by F1 76 Catalytic Process 76 Binding Change Model 76 Rotational Catalysis 77 Proton Translocation by F0 78 Peripheral Stalk 79 See Also the Following Articles 79 Glossary 79 Further Reading 79 FAK Family 80 FAK 80 FAK Expression and Role in Development 80 FAK Activation and Signaling Mechanism 80 Cellular Responses to FAK Signaling 81 PYK2 82 PYK2 Expression and Roles in Development 82 PYK2 Activation and Signaling Mechanism 82 Cellular Responses to PYK2 Signaling 82 Invertebrate Members of the FAK Family 83 See Also the Following Articles 83 Glossary 83 Further Reading 83 Fat Mobilization: Perilipin and Hormone-Sensitive Lipase 85 Plant Lipid Droplets 85 Animal Lipid Droplets 85 Perilipin 85 Perilipin Function 86 Adipocyte Lipolysis Catalyzed by Hormone-Sensitive Lipase 87 Lipolysis Model 88 See Also the Following Articles 88 Glossary 88 Further Reading 88 Fatty Acid Oxidation 90 Cellular Uptake and Activation of Fatty Acids 90 Fatty Acid Oxidation in Mitochondria 90 Mitochondrial Uptake of Fatty Acids 90 Beta-Oxidation in Mitochondria 91 Beta-Oxidation of Unsaturated Fatty Acids 92 Regulation of Mitochondrial Fatty Acid Oxidation 92 Fatty Acid Oxidation in Peroxisomes 93 Alpha-Oxidation and -Oxidation 93 See Also the Following Articles 94 Glossary 94 Further Reading 94 Fatty Acid Receptors 95 The PPAR Family of Receptors 95 PPARAlpha 95 PPARDelta 95 PPARGamma 96 The FFAR Family of Receptors 96 FFA1R 97 FFA2R 97 FFA3R 97 See Also The Following Articles 97 Glossary 97 Further Reading 97 Fatty Acid Synthesis and its Regulation 99 De novo Fatty Acid Biosynthesis of Saturated Fatty Acids 99 Regulation of Pyruvate Entry into Mitochondria 100 Regulation of Malonyl-CoA Synthesis 100 Malonyl-CoA and Fatty Acid Metabolism 100 Nutritional Regulation of Lipogenic Gene Expression 100 Carbohydrate Induction of Lipogenic Gene Transcription 101 Suppression of Lipogenic Gene Expression by Omega-6 and -3 Fatty Acids 101 Unsaturated Fatty Acid Synthesis 102 Oleic and Palmitoleic Acid Synthesis 102 Arachidonic and Docosahexenoic Acid Synthesis 102 See Also the Following Articles 103 Glossary 103 Further Reading 103 Ferredoxin 104 2Fe Ferredoxins 104 Plant-Type 2Fe Fds 104 Mitochondrial-Type 2Fe Fds 105 Thioredoxin-Type 2Fe Ferredoxins 106 Ferredoxins Containing 4Fe and 3Fe Iron-Sulfur Clusters 106 See Also The Following Articles 106 Glossary 106 Further Reading 106 Ferredoxin-NADP+ Reductase 107 Introduction 107 Photosynthetic FNR 107 Molecular Structure 107 Subcellular Localization and Physiological Role 108 Catalytic Mechanism 108 Non-Photosynthetic Plant-Type FNRs 109 Root FNR 109 Bacterial and Apicomplexan FNR 110 Heterotrophic Glutathione Reductase-Type FNRs 110 See Also the Following Articles 111 Glossary 111 Further Reading 111 Fibroblast Growth Factor Receptors and Cancer-Associated Perturbations 112 Fibroblast Growth Factors 112 Genes 112 Proteins 112 Physiologic Actions 112 Fibroblast Growth Factor Receptors 112 Genes 112 Proteins 113 Physiologic Actions 113 FGF Actions in Cancer 114 FGF2 114 FGF1 114 FGF3 114 FGF-4 114 FGF5 115 FGF6 115 FGF7 115 FGF8 115 FGF9-23 115 FGFR Actions in Cancer 115 FGFR1 115 FGFR2 116 FGFR3 116 FGFR4 116 Summary 117 See Also the Following Articles 117 Glossary 117 Further Reading 117 Flavins 118 Chemistry 118 Redox Properties 118 Oxygen and Other Derivatives 119 Spectroscopic Properties 119 Types of Flavoproteins 120 Pyridine Nucleotide Oxidoreductases 120 Dehydrogenase/Electron Transferase 120 Electron Transfer Proteins 120 Oxygenases 120 Oxidases 121 Photochemistry 121 Medical Significance 121 See Also the Following Articles 122 Glossary 122 Further Reading 122 Flippases 123 Introduction 123 Expansion of the ER Bilayer during Membrane Biogenesis 123 Aminophospholipid Flippases/Translocases, Floppases, Scramblases, and Phospholipid Asymmetry 124 Protein N-Glycosylation 125 Relationship of a Man-P-Dol Flippase to the Biosynthesis of Other Mannose-Containing Glycoconjugates 125 Protein O- and C-Mannosylation 125 GPI Anchors 126 Glucosylceramide 126 Bacterial Cell Walls 126 See Also the Following Articles 126 Glossary 126 Further Reading 126 Focal Adhesions 128 Cell Adhesion 128 Focal Adhesions-A Historical Perspective 128 The Molecular Organization of Focal Adhesions 128 The Receptors and their ECM Ligands 129 The Cytoskeletal Domain 129 The Submembrane Plaque 130 Diversity of Cell-Matrix Adhesion Sites 131 Signaling 132 Focal Adhesions and Mechanosensitivity 132 See Also the Following Articles 133 Glossary 133 Further Reading 133 Free Radicals, Sources and Targets of: Mitochondria 134 Introduction 134 The Mitochondrial Production of O2.- and H2O2 135 The Mitochondrial Production of .NO 136 The Physiological Role of the Mitochondrial Production of O2.-, H2O2, and .NO 139 Oxidative Stress and Dysfunctional Mitochondria: Mitochondria as Targets of Free Radicals 140 Mitochondrion-Dependent Apoptosis 140 The Mitochondrial Hypothesis of Aging 141 See Also the Following Articles 141 Glossary 141 Further Reading 142 Friedreich’s Ataxia 143 Historical Perspective 143 Clinical Features 143 Pathology 143 Genetics 143 Phenotype-Genotype Correlations 144 Gene and Gene Product 144 Therapeutic Intervention 144 See Also the Following Articles 145 Glossary 145 Further Reading 145 G Protein Signaling Regulators 146 Discovery of Regulators of G Protein Signaling 146 Structure of RGS Proteins 146 Mechanisms of RGS Proteins 147 Selectivity of RGS Action 147 Significance of RGS Action 148 Regulation of RGS Proteins 149 RGS Proteins as Drug Targets 149 See Also the Following Articles 150 Glossary 150 Further Reading 150 G Protein-Coupled Receptor Kinases and Arrestins 151 The GRK Family of Proteins 151 Specificity of GRK Interaction with GPCRs 151 Regulation of GRK Function 153 Structural Basis of GRK Function 153 Role of GRKs in Disease 153 The Arrestin Family of Proteins 154 Molecular Nature of Arrestin Interaction with GPCRs 154 Role of Arrestins in GPCR Endocytosis 154 Role of Arrestins as Scaffolds in Cell Signaling 155 The Structural Basis for Arrestin Function 155 See Also The Following Articles 155 Glossary 155 Further Reading 155 G12/G13 Family 157 General Properties and Modifications 157 Receptor-Mediated Activation of G12 and G13 157 Cellular Functions of G12/G13 157 Proteins Directly Interacting with G12/G13 158 In vivo Functions of G12/G13 159 See Also The Following Articles 159 Glossary 159 Further Reading 160 GABAA Receptor 161 Molecular Structure 161 Heteropentamers 161 A Family of Isoforms 161 Anatomical Localization and Functional Heterogeneity 161 Insights Gained from Transgenic Mice 162 Subcellular Localization, Associated Proteins, and Synaptic Plasticity 163 Functional Domains 164 Assembly 164 Ligand-Binding Sites 164 Ion Channel/Sites for Action of Allosteric Blockers and Enhancers 164 See Also The Following Articles 165 Glossary 165 Further Reading 165 GABAB Receptor 166 GABAB-Receptor Structure and Function 166 GABAB-Receptor Agonists and Allosteric Modulators 167 GABAB-Receptor Antagonists 168 Glossary 168 Further Reading 168 Galectins 170 Galectin Structure 170 Binding Specificity 170 Carbohydrate Structures 170 Glycoprotein Receptors 171 Galectin Distribution 171 Species 171 Tissues 171 Cells 172 Multiple Roles 172 Nuclear Functions 172 Cell Growth and Apoptosis 172 Cell Adhesion and Motility 172 Cancer and Metastasis 172 Immune Response and Regulation 173 See Also the Following Articles 173 Glossary 173 Further Reading 173 Genome-Wide Analysis of Gene Expression 174 Uses for Genome-Wide Expression Datasets 174 Using Gene Expression Data for Discovery 174 Using Gene Expression Data for Classification 174 Serial Methods for Global Analysis of Gene Expression 174 Analysis of Gene Expression Using Microarrays 175 Microarrays Created by Robotic Deposition or Ink-Jetting 175 Microarrays Synthesized in situ by Photolithography 175 Microarray Target Preparation and Hybridization 175 Microarray Data Analysis Methods 176 Analysis of Genome-Wide Expression Datasets 177 Cluster Analysis 177 Ontology Analysis 177 See Also The Following Articles 178 Glossary 178 Further Reading 178 Gi Family of Heterotrimeric G Proteins 180 Overview of the Gi Family 180 Signaling through GBetaGamma 180 Gi 181 Go 182 Gz 182 Gt (Transducin) 182 Gg (Gustducin) 183 Post-translational Modifications 183 See Also the Following Articles 183 Glossary 183 Further Reading 184 Giant Mitochondria (Megamitochondria) 185 Megamitochondrial Structure 185 Formation of Megamitochondria 185 Biochemistry 186 Involvement in Apoptosis 186 Restoration to Normal Size 186 See Also The Following Articles 187 Glossary 187 Further Reading 187 GlcNAc Biosynthesis and Function, O-Linked 188 Background 188 Biosynthesis of UDP-GlcNAc 188 O-GlcNAc Transferase (OGT) 188 O-GlcNAcase 189 Function 189 Physiological Importance 190 See Also The Following Articles 190 Glossary 191 Further Reading 191 Glucagon Family of Peptides and their Receptors 192 Pancreatic PGDPs 192 Glucagon 192 PGDPs in the Intestine and Brain 193 Secretion 193 Physiological Actions 193 Metabolism and Clearance 194 PGDP Receptors 194 See Also The Following Articles 195 Glossary 195 Further Reading 195 Gluconeogenesis 196 History 196 Overview of Gluconeogenesis 196 The Enzymes of Gluconeogenesis 196 Pyruvate Carboxylase (PC) 197 Phosphoenolpyruvate Carboxykinase (PEPCK) 197 Fructose-1,6-Bisphosphatase (FBPase) 198 Glucose-6-Phosphatase (G6Pase) 198 Physiological Control of Gluconeogenesis 198 Dietary Status Determines the Extent of Gluconeogenesis 198 The Role of Fatty Acid Oxidation in the Control of Gluconeogenesis 198 Pathway of Gluconeogenesis 199 Redox Balance for Gluconeogenesis 199 Regulation of Gluconeogenesis 199 Substrate Delivery to the Liver and Kidney 199 Mass Action Regulation of Enzymes 200 Allosteric Activation of Key Enzymes 200 Covalent Modification 200 Alteration in Gene Expression 200 Renal Gluconeogenesis 201 Final Words 201 See Also the Following Articles 201 Glossary 201 Further Reading 202 Glucose/Sugar Transport in Bacteria 203 The Phosphoenolpyruvate: Sugar Phosphotransferase System (PTS) 203 Classification 203 Functional Properties 203 Assembly and Phosphoryl Transfer Reaction 203 Preferential Utilizationof Carbohydrate 203 Electrochemical Ion-Gradient-Driven Symporters 204 Classification 204 Structural Features 204 Functional Properties 204 Representatives 205 Binding Protein-Dependent ATP-Binding Cassette (ABC) Transport System 205 Classification 205 Structural Architecture 205 Functional Properties 206 Maltodextrin/Maltose Transport 206 See Also the Following Articles 206 Glossary 206 Further Reading 206 Glucose/Sugar Transport in Mammals 207 Sodium-Dependent Glucose Transporters 207 Facilitative Glucose Transporters 207 GLUT1 208 GLUT2 209 GLUT3 209 GLUT4 209 GLUT5 210 GLUT6 210 GLUT7 210 GLUT8 210 GLUT9-14 210 See Also The Following Articles 210 Glossary 210 Further Reading 210 Glutamate Receptors, Ionotropic 212 Ionotropic Glutamate Receptor Subtypes 212 Ionotropic Glutamate Receptor Structure 212 Extracellular and Ligand-Binding Domains 212 Pore Structure 212 Intracellular Domain 213 Ionotropic Glutamate Receptor Subunits and Molecular Diversity 213 AMPA Receptors 214 Kainate Receptors 215 NMDA Receptors 215 Orphan (Delta) Receptors 215 Ionotropic Glutamate Receptor Pharmacology and Physiology 215 AMPA Receptor Physiology 216 Kainate Receptor Physiology 216 NMDA Receptor Physiology 217 Summary 217 See Also The Following Articles 217 Glossary 217 Further Reading 217 Glutamate Receptors, Metabotropic 219 Fast Synaptic Transmission and Neuromodulation in the Central Nervous System 219 Fast Excitatory and Neuromodulatory Actions of Glutamate 219 Eight mGlu Receptor Subtypes 220 mGlu Receptors Play Diverse Roles in Regulating Neuronal Excitability and Synaptic Transmission 220 Therapeutic Potential of mGlu Receptor Ligands 221 See Also The Following Articles 221 Glossary 221 Further Reading 222 Glutathione Peroxidases 223 History 223 Enzymology and Kinetics 223 Biosynthesis of Selenoperoxidases 225 Biological Functions 225 CGPX 225 PGPX 225 GI-GPx 226 PHGPx 226 Future Perspectives 226 See Also the Following Article 227 Glossary 227 Further Reading 227 Glycation 228 Glycation of Proteins in Blood 228 Glycated Hemoglobin 228 Clinical Significance of Glycated Hb 228 Glycation of Extracellular and Plasma Proteins 229 Glycation of Other Amino Acids and Biomolecules 229 Reactivity of Glucose 230 Advanced Glycation and Glycoxidation Reactions 230 Advanced Glycation 230 Glycoxidation 230 Alternative Pathways to AGEs and Glycoxidation Products 232 Recognition and Turnover of AGE-Proteins 232 The Maillard Reaction in Aging and Disease 232 Aging 232 Diabetes 233 AGE Inhibitors 234 Other Diseases 234 See Also The Following Articles 234 Glossary 234 Further Reading 234 Glycine Receptors 236 Distribution of Glycine in the Brain 236 Physiological Role and Functional Properties of Glycine Neurotransmission 236 Principal Properties of Glycinergic Inhibition 236 Roles in Spinal Control of Motor Activity and Sensory Processing 236 Synaptic Versus Extrasynaptic Inhibition 236 Long-Term Plasticity of Glycinergic Synapses 237 Switch from Excitatory to Inhibitory GlyR Function During Development 237 Mixed GABA and Glycinergic Synapses 237 Structure and Diversity of GlyR Channels 238 Purification and Isolation of the GlyR 238 Glycine Receptor Isoforms 238 Spatial and Developmental Expression of GlyR Subunits in the Brain 238 Heterologous Expression of the GlyR 238 Structural Features of the GlyR 238 Molecular Model of the Ligand-Binding Region 238 Ion Channel Function 238 The Cytoplasmic Loop of the Beta-Subunit is Crucial for Postsynaptic Receptor Clustering 240 Pharmacological Properties of the GlyR 240 The Classical Antagonist Strychnine 240 Agonistic Amino Acids 240 Antagonism by Channel Block 240 Allosteric Modulation of the GlyR 240 Disorders of Glycinergic Neurotransmission 241 Human Disorders 241 Animal Mutants 241 See Also the Following Articles 241 Glossary 241 Further Reading 241 Glycogen Metabolism 243 Glycogen Structure 243 Glycogen Metabolism 243 Synthesis 243 Degradation 243 Glycogen Function and Control 243 Metabolic Role 243 Role in Muscle or Exercise 245 Glycogen and Disease 246 Glycogen Storage Diseases 246 Diabetes Mellitus 246 See Also the Following Articles 246 Glossary 246 Further Reading 246 Glycogen Storage Diseases 248 Glycogen Structure 248 Glycogen Function 248 Glycogen Metabolism 248 Glycogen Synthesis 248 Glycogen Degradation 248 Control of Glycogen Metabolism 249 Defects in Glycogen Metabolism and their Consequences 250 Type I(a,b,c) 251 Type II 251 Type III 252 Type IV 252 Type V 252 Type VI 252 Type VII 252 Type IX 252 Summary 253 See Also the Following Articles 253 Glossary 253 Further Reading 253 Glycogen Synthase Kinase-3 254 GSK-3 Genes and Proteins 254 Regulation of GSK-3 254 A Primer on GSK-3 Substrates 256 Physiological Functions of GSK-3 257 Neurological Diseases 257 Knockout Mice 258 Metabolism and Diabetes 258 See Also the Following Articles 258 Glossary 258 Further Reading 258 Glycolipid-Dependent Adhesion Processes 260 GSL Assembly in Membrane as GSL-Enriched Microdomain 260 Cluster Formation by GSL-to-GSL Cis Interaction 260 Association of Clustered GSLs with Lipophilic Signal Transducers and Proteolipids: Assembly of ‘‘Glycosynapse’’ 260 Cell Adhesion through Clustered GSLs 260 Types of Cell Adhesion Mediated by GSL-to-GSL Interaction 261 Mouse Melanoma B16 Cell Adhesion to Mouse Endothelial Cells Through GM3-to-LacCer or GM3-to-Gg3Cer Interaction 261 F9 Cell Autoaggregation Through Lex-to-Lex Interaction 262 Human Embryonal Carcinoma Autoaggregation Through Gb4-to-nLc4 or Gb4-to-Gb5 Interaction 262 Rainbow Trout Sperm Binding to Egg Mediated by (KDN)GM3 Interaction with Gg3-Like Epitope 262 Types of Cell Adhesion Mediated by Interaction of GSL with GSL-Binding Protein 263 Neuronal Axon Binding to Myelin through Interaction of Ganglioside with Siglec-4 263 Aggregation of Renal Cell Carcinoma TOS1 Cells with Peripheral Blood Mononuclear Cells Through Interaction of ... 263 Adhesion of Neutrophils or Myelogenous Leukemia HL60 Cells to E-Selectin Through Fucosyl-poly-LacNAc Ganglioside... 263 Human Neuroblastoma Adhesion Through GM1-to-Galectin-1 Interaction 264 See Also the Following Articles 264 Glossary 264 Further Reading 264 Glycolysis, Overview 265 Role of Glycolysis 265 ATP Production 265 Preparatory Pathway for Glucose Oxidation 265 Three Stages of the Glycolytic Pathway 265 Priming Stage 266 Splitting Stage 266 Energy-Trapping Stage 266 Anaerobic Glycolysis is a Type of Fermentation 266 Control of Glycolysis 267 ATP Turnover 267 Oxygen 268 Cancer 268 Lactic Acidosis 269 See Also The Following Articles 269 Glossary 270 Further Reading 270 Glycoprotein Folding and Processing Reactions 271 Protein Folding in the Endoplasmic Reticulum 271 N-Glycan Processing Reactions in the Endoplasmic Reticulum 271 The UDP-Glc:glycoprotein Glucosyltransferase 273 The Quality Control Mechanism of Glycoprotein Folding 274 See Also the Following Articles 275 Glossary 275 Further Reading 275 Glycoprotein-Mediated Cell Interactions, O-Linked 276 Classes of O-Glycans 276 O-Fucose on Epidermal Growth Factor-Like Repeats 276 O-Glucose on EGF Repeats 277 O-Fucose on TSRs 277 O-Mannose 277 Functions of O-Glycans 278 The Role of O-Fucose in Regulating Signal Transduction 279 The Role of O-Mannose in Alpha-Dystroglycan Function 280 Potential Roles for O-Glucose on EGF-Like Repeats and O-Fucose on TSRs 280 See Also the Following Articles 280 Glossary 280 Further Reading 281 Glycoproteins, N-Linked 282 Biosynthesis and Structures of N-Linked Oligosaccharides 282 Synthesis of a dolichol pyrophosphate-Linked oligosaccharide 282 Transfer of the preformed oligosaccharide unit to newly synthesized protein 282 Glycosidase Digestion in the ER Lumen 283 Remodeling by Golgi apparatus glycosidases and glycosyltransferases 284 Methods for Analysis of N-Linked Glycoprotein Structure and Function 286 Binding to plant lectins 286 Radiolabeling of oligosaccharides 286 Digestion with purified endo- and exo-glycosidases 286 Inhibitors of glycan assembly and processing 287 Introduction of mutations in genes encoding glycosidases and glycosytransferases 287 Chemical and physical analysis of N-glycans 287 N-Linked Oligosaccharides as Experimental Aids 288 Purification of N-Linked Glycoproteins 288 Radiolabeling and Tagging of N-Linked Glycoproteins 288 Trafficking Through the Secretory Pathway 289 Functions of Selected N-Linked Glycans and their Specific Cognate Lectins 289 Monoglucosylated Oligosaccharides in ER Quality Control 289 High-Mannose Oligosaccharides Bearing Mannose-6-Phosphate Residues as Sorting Signals for Lysosomal Hydrolases 290 See Also the Following Articles 290 Glossary 290 Further Reading 290 Glycoproteins, Plant 292 Types of Glycosylation 292 N-Linked Glycans 292 O-Linked Glycans 292 Synthesis of O-Linked Glycans 293 Hydroxylation of proline 293 Glycosyl transferases 293 Arrangement of Hyp residues dictates the type of glycans 293 Hyp-Rich Glycoproteins Belong to Multigene Families 294 Approaches for Determining the Function of Plant Glycoproteins 294 Structural studies 294 Immunohistochemistry 295 Genetic approaches 295 Future Studies 295 See Also The Following Articles 295 Glossary 295 Further Reading 295 Glycosylation in Cystic Fibrosis 296 Cystic Fibrosis 296 Glycosylation 296 Terminal Glycosylation of CF Cells 297 CF Glycosylation Phenotype 297 Glycosylation of CF Fibroblasts 297 Glycosylation of CF Airway Epithelial Cells 297 Glycosylation of CF Airway Mucins 298 Functional Implications of Altered Glycosylation 299 See Also The Following Articles 299 Glossary 299 Further Reading 299 Glycosylation, Congenital Disorders of 301 Setting the Stage 301 Congenital Disorders of Glycosylation 301 Biosynthetic Overview 301 Scope of the Disorders 302 Laboratory Diagnosis of CDG 303 Biochemical Overview 303 Clinical Features of CDG 303 Therapy for CDG 303 Congenital Muscular Dystrophies: The Most Recently Discovered Glycosylation Deficiencies 305 Defects in Proteoglycan Biosynthesis Cause Disease 305 Glycosylation Disorders: The Next Generation 305 See Also the Following Articles 305 glossary 305 Further Reading 306 Glycosylphosphatidylinositol (GPI) Anchors 307 GPI Structure 307 GPI Biosynthesis 307 Outline of the Biosynthetic Pathway 307 GPI Attachment to Proteins 308 GPI-Anchoring in Mammals, Parasitic Protozoa, and Yeast 308 Functions of GPIs 309 Acknowledgments 310 See Also the Following Articles 310 Glossary 310 Further Reading 310 Golgi Complex 311 Morphology of the Golgi Complex 311 Protein Processing in the Golgi Complex 311 Protein Glycosylation 311 Proteolytic Processing 312 Mechanisms of Protein Transport at the Golgi Complex 312 Vesicular Transport at the Golgi Complex 312 Cisternal Progression 313 Protein Sorting at the Golgi Complex 313 Receptor-Mediated Sorting into Transport Vesicles 313 Protein Aggregation as a Sorting Mechanism 313 See Also The Following Articles 314 Glossary 314 Further Reading 314 Gq Family 315 Gq Family of G Proteins 315 Gq is Activated by Hormones, Neurotransmitters, and Drugs through Multiple GPCRs 315 PLCBeta Activation and Calcium Mobilization are Downstream Responses to Gq Activation 315 Gq in Cardiovascular Disease, Platelet Aggregation, and Cerebellum Development 317 Modulation of Gq Functions 318 Gq Family Members are Functionally Complementary to Each Other 318 See Also the Following Articles 319 Glossary 319 Further Reading 319 Green Bacteria: Secondary Electron Donor (Cytochromes) 320 Cytochromes in Green Bacteria 320 Types of c-Type Cytochromes in Green Sulfur Bacteria 320 Cytochrome cz (PscC) 321 Cytochrome c-555 321 Cytochrome c-553 (Fcc/SoxEF1) 321 Cytochrome c-551 (SoxA) 321 Cytochrome bc1 Complex 322 Other Cytochromes in Green Sulfur Bacteria 322 Cytochromes in Filamentous Anoxygenic Phototrophic Bacteria 322 Cytochrome c-554 322 Other Cytochromes in Filamentous Anoxygenic Phototrophic Bacteria 322 See Also The Following Articles 322 Glossary 322 Further Reading 322 Green Bacteria: The Light-Harvesting Chlorosome 324 Phylogeny 324 Structural Features 324 Size and Internal Structure 324 Proteins 325 Carotenoids 325 Spectral Properties 325 Models of Chlorophyll Organization 325 Energy Transfer 328 Evolutionary Considerations 328 See Also the Following Articles 328 Glossary 328 Further Reading 328 Green Sulfur Bacteria: Reaction Center and Electron Transport 330 Light Capture 330 Chlorosomes 330 The FMO Protein 330 The Homodimeric P840-Reaction Center - Composition, Structure, and Electron Transfer 330 Secondary Electron Donors and Acceptors 333 Further Genes For Electron Transport Components 334 See Also the Following Articles 334 Glossary 334 Further Reading 334 Gs Family of Heterotrimeric G Proteins 336 G Protein-Mediated Signal Transduction 336 Discovery 336 Regulation of G Proteins by Guanine Nucleotides 336 Members of the Family 338 GAlphas 338 GAlphaolf 338 Structure 339 Nucleotide-Bound Protein 339 Covalent Modifications 339 Gs Dysfunction in Human Disease 339 Cholera 339 Genetic Mutations 340 See Also the Following Articles 340 Glossary 340 Further Reading 340 Heat/Stress Resp Cover Page......Page 843 Editors-in-Chief......Page 777 Associate Editors......Page 779 Preface......Page 782 Notes on the Subject Index......Page 783 Volume 1......Page 784 Volume 2......Page 792 Volume 3......Page 800 Volume 4......Page 808 Lipids, Carbohydrates, Membranes and Membrane Proteins......Page 813 Metabolism, Vitamins and Hormones......Page 815 Cell Architecture and Function......Page 817 Protein/Enzyme Structure Function and Degradation......Page 820 Bioenergetics......Page 823 Molecular Biology......Page 829 Signaling......Page 835 Techniques and Methodology......Page 842 Volume 4 (S-Z)......Page 0 Elongation Factor EF-Tu......Page 1 The Ternary Complex of EF-Tu......Page 3 Antibiotic Action on EF-Tu......Page 4 Further Reading......Page 5 Eicosanoid Action......Page 6 Prostaglandin (PG) Receptors......Page 7 Glossary......Page 8 Further Reading......Page 9 Soluble Elastin......Page 10 Posttranscriptional Regulation......Page 11 Further Reading......Page 12 Deactivation......Page 13 Cannabinoid Receptors......Page 14 Further Reading......Page 15 Dynamin......Page 16 Clathrin-Independent Endocytosis......Page 17 Fate of Internalized Membrane and Content......Page 18 Further Reading......Page 19 Protein Synthesis and Folding in the ER......Page 20 Distinct ER Chaperone Networks are Involved in the GERAD Process......Page 21 See Also the Following Articles......Page 22 Further Reading......Page 23 Fermentation......Page 24 Electron Transport Phosphorylation in Anaerobic Respiration......Page 26 Decarboxylation of Dicarboxylic Acids......Page 28 Anoxygenic Photosynthetic Prokaryotes......Page 29 Further Reading......Page 30 Transition-State Analogues......Page 31 Noncatalytic Site Inhibitors......Page 34 Polyamine Synthesis......Page 35 Conclusion......Page 36 Further Reading......Page 37 The Rapid Equilibrium Assumption......Page 38 A More Realistic Unireactant Reaction Sequence......Page 39 The Velocity Curve and its Linear Forms......Page 40 Velocity Equations for Some Bireactant Mechanisms......Page 41 Further Reading......Page 44 Stereoselectivity, Stereospecificity, and Stereochemical Course of Enzymatic Reactions......Page 45 Analysis of Steric Course to Probe an Enzymatic Reaction Pathway......Page 47 Stereoselectivity Can Probe Metal-Nucleotide or Enzyme-Substrate Interactions at the Transition State......Page 48 Further Reading......Page 49 The Structure of ErbB Receptors......Page 51 ErbB Receptor Substrates......Page 52 Receptor-Mediated Endocytosis......Page 53 Further Reading......Page 54 The Partial Reactions of the Catalytic and Transport Cycles......Page 56 Ca2+ Binding and Catalytic Activation......Page 58 Physiological Regulation and Experimental Inhibitors......Page 59 Further Reading......Page 60 Details of the Ca2+-Binding Sites......Page 61 Rearrangement of the Transmembrane Helices......Page 63 Role of the Large Conformational Movements......Page 64 Further Reading......Page 65 Mechanism......Page 66 Processivity......Page 68 FEN-1/5 Nucleases......Page 69 Replication Fidelity......Page 70 Further Reading......Page 71 Subunit Composition......Page 73 F0......Page 75 Binding Change Model......Page 76 Rotational Catalysis......Page 77 Proton Translocation by F0......Page 78 Further Reading......Page 79 FAK Activation and Signaling Mechanism......Page 80 Cellular Responses to FAK Signaling......Page 81 Cellular Responses to PYK2 Signaling......Page 82 Further Reading......Page 83 Perilipin......Page 85 Perilipin Function......Page 86 Adipocyte Lipolysis Catalyzed by Hormone-Sensitive Lipase......Page 87 Further Reading......Page 88 Mitochondrial Uptake of Fatty Acids......Page 90 Beta-Oxidation in Mitochondria......Page 91 Regulation of Mitochondrial Fatty Acid Oxidation......Page 92 Alpha-Oxidation and -Oxidation......Page 93 Further Reading......Page 94 PPARDelta......Page 95 The FFAR Family of Receptors......Page 96 Further Reading......Page 97 De novo Fatty Acid Biosynthesis of Saturated Fatty Acids......Page 99 Nutritional Regulation of Lipogenic Gene Expression......Page 100 Suppression of Lipogenic Gene Expression by Omega-6 and -3 Fatty Acids......Page 101 Arachidonic and Docosahexenoic Acid Synthesis......Page 102 Further Reading......Page 103 Plant-Type 2Fe Fds......Page 104 Mitochondrial-Type 2Fe Fds......Page 105 Further Reading......Page 106 Molecular Structure......Page 107 Catalytic Mechanism......Page 108 Root FNR......Page 109 Heterotrophic Glutathione Reductase-Type FNRs......Page 110 Further Reading......Page 111 Genes......Page 112 Physiologic Actions......Page 113 FGF-4......Page 114 FGFR1......Page 115 FGFR4......Page 116 Further Reading......Page 117 Redox Properties......Page 118 Spectroscopic Properties......Page 119 Oxygenases......Page 120 Medical Significance......Page 121 Further Reading......Page 122 Expansion of the ER Bilayer during Membrane Biogenesis......Page 123 Aminophospholipid Flippases/Translocases, Floppases, Scramblases, and Phospholipid Asymmetry......Page 124 Protein O- and C-Mannosylation......Page 125 Further Reading......Page 126 The Molecular Organization of Focal Adhesions......Page 128 The Cytoskeletal Domain......Page 129 The Submembrane Plaque......Page 130 Diversity of Cell-Matrix Adhesion Sites......Page 131 Focal Adhesions and Mechanosensitivity......Page 132 Further Reading......Page 133 Introduction......Page 134 The Mitochondrial Production of O2.- and H2O2......Page 135 The Mitochondrial Production of .NO......Page 136 The Physiological Role of the Mitochondrial Production of O2.-, H2O2, and .NO......Page 139 Mitochondrion-Dependent Apoptosis......Page 140 Glossary......Page 141 Further Reading......Page 142 Genetics......Page 143 Therapeutic Intervention......Page 144 Further Reading......Page 145 Structure of RGS Proteins......Page 146 Selectivity of RGS Action......Page 147 Significance of RGS Action......Page 148 RGS Proteins as Drug Targets......Page 149 Further Reading......Page 150 Specificity of GRK Interaction with GPCRs......Page 151 Role of GRKs in Disease......Page 153 Role of Arrestins in GPCR Endocytosis......Page 154 Further Reading......Page 155 Cellular Functions of G12/G13......Page 157 Proteins Directly Interacting with G12/G13......Page 158 Glossary......Page 159 Further Reading......Page 160 Anatomical Localization and Functional Heterogeneity......Page 161 Insights Gained from Transgenic Mice......Page 162 Subcellular Localization, Associated Proteins, and Synaptic Plasticity......Page 163 Ion Channel/Sites for Action of Allosteric Blockers and Enhancers......Page 164 Further Reading......Page 165 GABAB-Receptor Structure and Function......Page 166 GABAB-Receptor Agonists and Allosteric Modulators......Page 167 Further Reading......Page 168 Carbohydrate Structures......Page 170 Tissues......Page 171 Cancer and Metastasis......Page 172 Further Reading......Page 173 Serial Methods for Global Analysis of Gene Expression......Page 174 Microarray Target Preparation and Hybridization......Page 175 Microarray Data Analysis Methods......Page 176 Ontology Analysis......Page 177 Further Reading......Page 178 Signaling through GBetaGamma......Page 180 Gi......Page 181 Gt (Transducin)......Page 182 Glossary......Page 183 Further Reading......Page 184 Formation of Megamitochondria......Page 185 Restoration to Normal Size......Page 186 Further Reading......Page 187 O-GlcNAc Transferase (OGT)......Page 188 Function......Page 189 See Also The Following Articles......Page 190 Further Reading......Page 191 Glucagon......Page 192 Physiological Actions......Page 193 PGDP Receptors......Page 194 Further Reading......Page 195 The Enzymes of Gluconeogenesis......Page 196 Phosphoenolpyruvate Carboxykinase (PEPCK)......Page 197 The Role of Fatty Acid Oxidation in the Control of Gluconeogenesis......Page 198 Substrate Delivery to the Liver and Kidney......Page 199 Alteration in Gene Expression......Page 200 Glossary......Page 201 Further Reading......Page 202 Preferential Utilizationof Carbohydrate......Page 203 Functional Properties......Page 204 Structural Architecture......Page 205 Further Reading......Page 206 Facilitative Glucose Transporters......Page 207 GLUT1......Page 208 GLUT4......Page 209 Further Reading......Page 210 Pore Structure......Page 212 Ionotropic Glutamate Receptor Subunits and Molecular Diversity......Page 213 AMPA Receptors......Page 214 Ionotropic Glutamate Receptor Pharmacology and Physiology......Page 215 Kainate Receptor Physiology......Page 216 Further Reading......Page 217 Fast Excitatory and Neuromodulatory Actions of Glutamate......Page 219 mGlu Receptors Play Diverse Roles in Regulating Neuronal Excitability and Synaptic Transmission......Page 220 Glossary......Page 221 Further Reading......Page 222 Enzymology and Kinetics......Page 223 PGPX......Page 225 Future Perspectives......Page 226 Further Reading......Page 227 Clinical Significance of Glycated Hb......Page 228 Glycation of Other Amino Acids and Biomolecules......Page 229 Glycoxidation......Page 230 Aging......Page 232 Diabetes......Page 233 Further Reading......Page 234 Synaptic Versus Extrasynaptic Inhibition......Page 236 Mixed GABA and Glycinergic Synapses......Page 237 Ion Channel Function......Page 238 Allosteric Modulation of the GlyR......Page 240 Further Reading......Page 241 Metabolic Role......Page 243 Role in Muscle or Exercise......Page 245 Further Reading......Page 246 Glycogen Degradation......Page 248 Control of Glycogen Metabolism......Page 249 Defects in Glycogen Metabolism and their Consequences......Page 250 Type II......Page 251 Type IX......Page 252 Further Reading......Page 253 Regulation of GSK-3......Page 254 A Primer on GSK-3 Substrates......Page 256 Neurological Diseases......Page 257 Further Reading......Page 258 Cell Adhesion through Clustered GSLs......Page 260 Mouse Melanoma B16 Cell Adhesion to Mouse Endothelial Cells Through GM3-to-LacCer or GM3-to-Gg3Cer Interaction......Page 261 Rainbow Trout Sperm Binding to Egg Mediated by (KDN)GM3 Interaction with Gg3-Like Epitope......Page 262 Adhesion of Neutrophils or Myelogenous Leukemia HL60 Cells to E-Selectin Through Fucosyl-poly-LacNAc Ganglioside.........Page 263 Further Reading......Page 264 Three Stages of the Glycolytic Pathway......Page 265 Anaerobic Glycolysis is a Type of Fermentation......Page 266 ATP Turnover......Page 267 Cancer......Page 268 See Also The Following Articles......Page 269 Further Reading......Page 270 N-Glycan Processing Reactions in the Endoplasmic Reticulum......Page 271 The UDP-Glc:glycoprotein Glucosyltransferase......Page 273 The Quality Control Mechanism of Glycoprotein Folding......Page 274 Further Reading......Page 275 O-Fucose on Epidermal Growth Factor-Like Repeats......Page 276 O-Mannose......Page 277 Functions of O-Glycans......Page 278 The Role of O-Fucose in Regulating Signal Transduction......Page 279 Glossary......Page 280 Further Reading......Page 281 Transfer of the preformed oligosaccharide unit to newly synthesized protein......Page 282 Glycosidase Digestion in the ER Lumen......Page 283 Remodeling by Golgi apparatus glycosidases and glycosyltransferases......Page 284 Digestion with purified endo- and exo-glycosidases......Page 286 Chemical and physical analysis of N-glycans......Page 287 Radiolabeling and Tagging of N-Linked Glycoproteins......Page 288 Monoglucosylated Oligosaccharides in ER Quality Control......Page 289 Further Reading......Page 290 O-Linked Glycans......Page 292 Arrangement of Hyp residues dictates the type of glycans......Page 293 Structural studies......Page 294 Further Reading......Page 295 Glycosylation......Page 296 Glycosylation of CF Airway Epithelial Cells......Page 297 Glycosylation of CF Airway Mucins......Page 298 Further Reading......Page 299 Biosynthetic Overview......Page 301 Scope of the Disorders......Page 302 Therapy for CDG......Page 303 glossary......Page 305 Further Reading......Page 306 Outline of the Biosynthetic Pathway......Page 307 GPI-Anchoring in Mammals, Parasitic Protozoa, and Yeast......Page 308 Functions of GPIs......Page 309 Further Reading......Page 310 Protein Glycosylation......Page 311 Vesicular Transport at the Golgi Complex......Page 312 Protein Aggregation as a Sorting Mechanism......Page 313 Further Reading......Page 314 PLCBeta Activation and Calcium Mobilization are Downstream Responses to Gq Activation......Page 315 Gq in Cardiovascular Disease, Platelet Aggregation, and Cerebellum Development......Page 317 Gq Family Members are Functionally Complementary to Each Other......Page 318 Further Reading......Page 319 Types of c-Type Cytochromes in Green Sulfur Bacteria......Page 320 Cytochrome c-551 (SoxA)......Page 321 Further Reading......Page 322 Size and Internal Structure......Page 324 Models of Chlorophyll Organization......Page 325 Further Reading......Page 328 The Homodimeric P840-Reaction Center - Composition, Structure, and Electron Transfer......Page 330 Secondary Electron Donors and Acceptors......Page 333 Further Reading......Page 334 Regulation of G Proteins by Guanine Nucleotides......Page 336 GAlphaolf......Page 338 Cholera......Page 339 Further Reading......Page 340 Stress Detection and Response......Page 341 The HSR Output......Page 342 The Unfolded Protein Response......Page 343 Glossary......Page 344 Further Reading......Page 345 Erythropoietin Receptor......Page 346 Thrombopoietin Receptor......Page 348 Signal Transduction through the GM-CSF/IL-3/IL-5 Receptor......Page 349 Further Reading......Page 350 Myoglobin......Page 352 Hemoglobin......Page 353 Peroxidases......Page 355 Catalases......Page 356 Cytochromes P450 Enzymes......Page 357 Cytochromes......Page 358 Further Reading......Page 359 Formation of 5-Aminolevulinate......Page 360 From ALA to Uroporphyrinogen III......Page 361 Regulation of the Heme Biosynthetic Pathway/Heme Biosynthesis......Page 362 Disorders of the Heme Biosynthetic Pathway......Page 363 Further Reading......Page 364 HGF/SF Receptor......Page 365 Structure......Page 366 Biological Activity......Page 367 The HGF/SF Receptor in Human Tumors......Page 368 Further Reading......Page 369 Diversity of Hexokinases and Glucokinases......Page 370 Classification and Evolution of Hexokinases......Page 371 Three-Dimensional Structure......Page 372 Sigmoidal Kinetics......Page 373 Glossary......Page 374 Further Reading......Page 375 H1 Agonists......Page 376 H1-Antagonists......Page 377 Histamine H3-Receptors......Page 378 Splice Variants of the H3-Receptor......Page 379 Further Reading......Page 380 Gag/Pol Polyprotein and Viral Assembly......Page 382 Mode of Inhibitor Binding......Page 383 HIV PR as a Model System for Analysis of Protein Structure/Function......Page 384 Further Reading......Page 385 Functional Implications of RT Structures......Page 386 Structural Basis of HIV-1 RT Drug Resistance......Page 388 Further Reading......Page 389 The Role of Recombination in Meiosis......Page 391 Initiation......Page 392 Gene Conversion......Page 393 See Also the Following Articles......Page 394 Further Reading......Page 395 Origin of the ‘‘Reversed-Phase’’ Term......Page 396 Supports for Small Tryptic Peptide Separations......Page 397 Mass Spectrometry Applications......Page 398 Guard Columns......Page 399 Size Separation......Page 400 Further Reading......Page 401 Specialized Light Microscopy Techniques......Page 402 Electronic Light Detectors......Page 403 CCD Sensors......Page 404 Confocal Laser Scanning Microscopy......Page 405 Digital Image Characteristics......Page 406 Further Reading......Page 407 IgG Receptors......Page 408 Receptor-Binding Sites in Immunoglobulin......Page 409 Non-Leukocyte FcRs......Page 410 Key Events in the Analysis of FcR......Page 412 Further Reading......Page 413 Iron......Page 414 Copper......Page 415 Rare Uses of Inorganic Elements......Page 416 Further Reading......Page 417 Protein Tyrosine Phosphatases......Page 418 PTEN and Myotubularin: PTP-Like Phosphoinositide Phosphatases......Page 419 PTEN......Page 420 Myotubularin......Page 421 Further Reading......Page 423 Inositol Phosphate Nomenclature......Page 424 Enzyme Nomenclature and Metabolic Interrelationships......Page 425 Further Reading......Page 426 The Beta-Cell Glucokinase Glucose Sensor and the Threshold for GSIR......Page 427 Model Experiments to Illustrate the Operation of the TPW and the APW......Page 428 Amino Acids and Fatty Acids as Glucose-Dependent Stimuli of Beta Cells......Page 429 Neuroendocrine Modification of Fuel-Stimulated Insulin Release......Page 430 Beta-Cell Therapy in T2DM and Hyperinsulinemia......Page 431 Further Reading......Page 432 Composition and Biosynthesis......Page 433 Autophosphorylation and Kinase Activation......Page 434 Signaling Cascades......Page 435 ‘‘Genetics’’ and IR-IGF1R Comparisons......Page 436 Further Reading......Page 437 General Features of Integrin Signaling......Page 438 Integrin Activation......Page 439 Integrins in Adhesion Sites......Page 440 Contributions to Cellular Phenotypes......Page 441 Further Reading......Page 442 Receptor Structure......Page 443 Effects of Signaling Through the IFN-Gamma Receptor......Page 444 Expression of IFN-Alpha/Beta and Their Receptor......Page 445 Signal Transduction......Page 446 Glossary......Page 447 Further Reading......Page 448 Expression and Subcellular Localization......Page 449 Molecular Interactions......Page 450 Structural Properties......Page 452 Further Reading......Page 453 Assembly and Structure......Page 455 Regulation......Page 456 Type V Lamins......Page 458 Apoptosis......Page 459 See Also the Following Articles......Page 460 Further Reading......Page 461 Cyclic Adenosine Diphosphate Ribose......Page 462 cADPR and Activation of Different RYR Isoforms......Page 463 Glossary......Page 464 Further Reading......Page 465 NAADP-Induced Ca2+-Release in Invertebrates and Plants......Page 466 Metabolism of NAADP......Page 468 Further Reading......Page 469 Voltage-Gated Sodium and Calcium Channels......Page 470 Second Messenger-Gated and Sensory Ion Channels......Page 471 Inwardly Rectifying Potassium Channels and their Relatives......Page 472 Structure and Function......Page 473 Further Reading......Page 474 Structure of IP3 Receptors......Page 475 IP3 Receptors are Regulated by IP3 and Ca2+......Page 477 Further Reading......Page 478 Properties......Page 479 Structure......Page 480 Functions......Page 482 General Overview......Page 483 Biogenesis of Fe-S Proteins in Bacteria......Page 484 Biogenesis of Fe-S Proteins in Eukaryotes......Page 485 Further Reading......Page 486 JAK Kinases......Page 487 The STATs......Page 490 Glossary......Page 491 Further Reading......Page 492 Keratin Gene Clusters Reflect Tissue Expression: Implications for Keratin Evolution......Page 493 Keratin Gene Expression Mirrors Epithelial Differentiation: The Case of Skin......Page 495 Keratin Gene Expression in Thick Epidermis......Page 497 Scaffolding Components of Signaling Pathways and Other Functions......Page 498 Glossary......Page 499 Further Reading......Page 500 Synthesis of Ketone Bodies......Page 501 Ketone Body Utilization......Page 502 Further Reading......Page 503 Kinesin Superfamily Proteins......Page 504 Kinesin Superfamily Proteins......Page 505 Kinesin Superfamily Proteins......Page 506 Kinesin Superfamily Proteins......Page 507 Kinesin Superfamily Proteins......Page 510 Kinesin Superfamily Proteins......Page 511 Further Reading......Page 512 Kinesins as Regulators of Microtubule Dynamics: A Brief Historical Overview......Page 513 Kin I Kinesins: Mechanism of Action......Page 514 Physiological Roles of Microtubule-Depolymerizing Kinesins......Page 516 Further Reading......Page 517 Wave/Particle Dualism......Page 518 Activation Energy and Transition State Theory......Page 519 Isotope Effects from Zero-Point Energies......Page 520 An Example From Glucose Oxidase Catalysis......Page 521 Further Reading......Page 523 Historical Perspective......Page 524 LacI Function......Page 525 LacI Structural Characteristics......Page 526 Implications for Complex Organisms......Page 528 Further Reading......Page 529 Molecular Properties......Page 530 Functions......Page 531 Applications......Page 533 Further Reading......Page 534 Central Mechanisms of Leptin Action......Page 536 Adipose Tissue as a Target of the SNS......Page 537 Regulation of Leptin Expression......Page 538 Leptin Resistance and Obesity......Page 539 Further Reading......Page 540 LexA Autoregulation......Page 541 LexA Mutants and Their Phenotype......Page 542 Other Bacterial LexA Regulatory Systems......Page 543 Further Reading......Page 544 Calcium Signaling in Neurons......Page 546 Physiological and Pharmacological Properties of Glutamate Receptors......Page 548 AMPA Receptor Genes and Protein Structure......Page 550 KA Receptor Genes and Protein Structure......Page 551 NMDA Receptor Genes and Protein Structure......Page 552 mGluR Genes and Proteins......Page 553 Glutamate Receptors, Ca2+-Signaling, and Synaptic Plasticity......Page 554 Glossary......Page 555 Further Reading......Page 556 Early GABAA Receptor Biochemistry......Page 557 Molecular Biology of the GABAA Receptor......Page 558 In Vitro Studies......Page 559 Subtly Altered Receptor Subunits Cause Diseases......Page 560 Further Reading......Page 561 The Protein Components......Page 562 The Pigment Components......Page 563 See Also the Following Articles......Page 564 Further Reading......Page 565 Hydrolysis Mechanism and Specificity......Page 566 Physiochemical Importance of Interfaces......Page 567 Structural Adaptation of Lipases at Interfaces......Page 568 Lipase Cofactors......Page 569 Further Reading......Page 570 Membrane Proteins and Bilayers......Page 571 Physical State of Bilayer Lipids......Page 572 Transverse Lipid Movements......Page 573 Further Reading......Page 574 Fatty Acylation......Page 575 Myristoylated and Farnesylated Proteins......Page 576 Membrane Targeting and Protein Function......Page 577 Further Reading......Page 578 Lipid Phase Behavior......Page 579 Functions of Rafts......Page 581 Further Reading......Page 582 Apolipoprotein B Lipoprotein Metabolism......Page 583 HDL Metabolism and Reverse Cholesterol Transport......Page 586 Pathologies of Lipoprotein Metabolism......Page 587 Further Reading......Page 588 Weak Hydrogen Bonds......Page 589 Bond Lengths......Page 590 Serine Proteases......Page 591 Glossary......Page 592 Further Reading......Page 593 Therapy......Page 594 Genetics......Page 595 Further Reading......Page 596 Plasma Membrane Receptors......Page 597 See Also The Following Articles......Page 598 Further Reading......Page 599 Clinical Relevance of MDR1......Page 600 The Conundrum of MDR1: Broad Specificity with High Affinity......Page 601 ABCG2......Page 602 Analogous Systems in Other Organisms......Page 603 Further Reading......Page 604 Mitosis......Page 605 Meiosis......Page 606 After Prophase I......Page 607 Loops and Axes......Page 608 Synaptonemal Complexes......Page 609 Homologous Recombination during Meiosis......Page 610 Further Reading......Page 611 Pigmentation......Page 612 Energy Homeostasis and Other CNS Actions......Page 613 See Also the Following Articles......Page 614 Further Reading......Page 615 Membrane Fusion......Page 616 Proteins......Page 617 Mechanistic Pathways......Page 618 Glossary......Page 620 Further Reading......Page 621 Diffusion through Pores or Channels (Restricted Diffusion)......Page 622 Facilitated Diffusion......Page 623 Active Transport......Page 624 Further Reading......Page 625 Discovery of the Na+/Ca2+ Exchanger......Page 626 An Expanding Gene Family......Page 627 Expression of NCX and NCKX in Mammals......Page 628 Functional Properties......Page 629 Physiological Relevance......Page 630 Further Reading......Page 631 Fermentation......Page 632 Anaerobic Respiration......Page 633 Oxygen Respiration......Page 634 Special Mechanisms in Archaeal Energy Transduction......Page 636 Methanogenesis......Page 637 Respiratory Complexes......Page 638 Glossary......Page 639 Further Reading......Page 640 Advantages of Metabolite Channeling......Page 641 The Creatine Kinase/Phosphocreatine Circuit or Shuttle......Page 642 Channeling in Energy Transducing Mitochondrial Microcompartments......Page 643 Mitochondrial CK and the Mitochondrial Permeability Transition Pore......Page 645 Further Reading......Page 646 Gelatinases......Page 652 Structural Chemistry......Page 655 Activation by Chemical and Physical Means......Page 656 Activity and Substrate Specificity......Page 657 TIMPs......Page 658 Glossary......Page 659 Further Reading......Page 660 The Physical Chromosome......Page 661 Teasing Apart Mitotic Chromosomes......Page 662 Identification of Other Proteins Playing Roles in Chromosome Dynamics......Page 663 Reversing the Process: Postsegregation Decondensation......Page 664 Mitotic Chromosome Architecture Is Coordinated with DNA Replication and Repair......Page 665 Further Reading......Page 666 Metal Sites......Page 647 Structural Sites......Page 648 Metalloprotease Inhibition......Page 649 Further Reading......Page 650 Histone Code......Page 667 Methyl-CpG-Binding Proteins......Page 668 MBD4......Page 669 Further Reading......Page 670 MAP1A and MAP1B......Page 671 MAP2A, MAP2B, and MAP2C......Page 672 Control of Microtubule Dynamics......Page 674 Analysis of Transgenic and Knockout Mice: Relation of MAPs to Neurodegenerative Diseases......Page 675 Further Reading......Page 676 Anti-M1 AMAs and Cardiolipin......Page 678 Anti-M2 AMAs......Page 679 Anti-M4 AMAs and Sulfite Oxidase......Page 681 AMAs Arising from Tissue Damage......Page 682 Further Reading......Page 683 OM Channels......Page 684 IM Channels......Page 685 Involvement of Mitochondrial Channels in Cell Death Mechanisms......Page 686 Further Reading......Page 687 Discovery of Mitochondrial DNA......Page 688 Sequence and Gene Content......Page 689 Outlook......Page 690 Further Reading......Page 691 Yeast as a Model Organism for the Study of Mitochondrial Biogenesis and Function......Page 692 Transcription......Page 693 Translation......Page 695 See Also The Following Articles......Page 696 Further Reading......Page 697 Genome Size Reduction and Accelerated Evolution in Early Mitochondrial History......Page 698 Ongoing Gene Transfer to the Nucleus......Page 699 Limitation of Gene Transfer to the Nucleus......Page 700 Animal mtDNAs......Page 701 Glossary......Page 702 Further Reading......Page 703 Structure, Biology, and Origins......Page 704 MtDNA Variation and Human Adaptation to Cold......Page 707 Somatic mtDNA Mutations in Aging......Page 709 Further Reading......Page 710 Structure of Mitochondrial Genomes......Page 711 Transmission of Mitochondrial DNA between Generations......Page 712 Further Reading......Page 713 Mitochondrial Membranes and Compartments......Page 715 Functional Implications of the Cristae Junctions......Page 716 Inner Membrane Fusion and Fission......Page 717 See Also the Following Articles......Page 718 Further Reading......Page 719 Structure......Page 720 Extension of the Mitochondrial Carrier Family......Page 721 Driving Forces for Transport......Page 722 Functional Models for Mitochondrial Exchange Carriers......Page 725 Structure and Function Studies: The Use of Mutant Proteins......Page 726 Further Reading......Page 727 Functions of the Outer Membrane......Page 728 VDAC Function and Dynamics......Page 729 The Outer Membrane and Apoptosis......Page 730 Further Reading......Page 731 ERK1 and ERK2......Page 732 p38s (p38Alpha, p38Beta, p38Gamma, p38Delta)......Page 733 ERK5......Page 734 Specificity and Fidelity in Nuclear Signal Transmission by MAPK Signaling Pathways......Page 735 Further Reading......Page 736 Prophase......Page 738 Prometaphase......Page 739 Metaphase......Page 740 Anaphase......Page 741 Further Reading......Page 742 Sequences Upstream of the Poly A Site......Page 743 Cleavage Stimulation Factor......Page 744 Transcription Termination and Polyadenylation are Linked......Page 745 Glossary......Page 746 Further Reading......Page 747 Ribonucleases that Mediate mRNA Degradation in the Bacterium Escherichia coli......Page 748 The Degradosome, a Multiprotein Complex for RNA Degradation......Page 749 Polyadenylation Maintains the Momentum of mRNA Decay......Page 750 Decay Pathways Vary with the Position of the Initiating Cleavage......Page 751 Further Reading......Page 752 Mucin Subtypes......Page 753 Roles in Health and Diseases......Page 754 Major Nonmucin Domains in Secreted Mucins......Page 755 Secreted (Gel-Forming) Mucins......Page 757 See Also the Following Articles......Page 758 Further Reading......Page 759 Functions......Page 760 Expression......Page 762 Summary and Future Directions......Page 763 Further Reading......Page 764 Nucleotide Sequences......Page 765 Multiple Alignments......Page 766 Constructing Phylogenetic Trees......Page 767 Further Reading......Page 768 Muscarinic Receptor-Mediated Regulation of Second Messenger Pathways......Page 770 Regions of the mAChR Involved in Coupling to G Proteins......Page 771 Further Reading......Page 772 Evolutionary Diversity and Phylogenic Classification......Page 773 Mechano-Chemical Features and Regulation......Page 774 A Multitude of Cellular Functions......Page 775 Further Reading......Page 776

Written for a broad, cross-disciplinary audience, the Encyclopedia of Biological Chemistry addresses the fundamental discipline of biological chemistry underlying virtually all of the life sciences. This compilation of more than 500 different entries encompasses all aspects of biochemistry, as well as the extensions of this subject into the related fields of molecular biology, cell biology, genetics and biophysics. This comprehensive encyclopedia covers all areas of biological chemistry written by more than 500 selected international experts. Articles are generously illustrated including more than 800 images in four-color. Each entry contains a clear, concise review of the topic along with illustrations, a glossary of technical terms and a section for additional reading.

Each entry further contains general background and term definitions as well as a comprehensive review of the current research in the field. Students, science journalists and scientists seeking a concise introduction to specific topics will appreciate the clear, tabular format of each entry.

Also available online via ScienceDirect - featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com.

*Four-volume set with topics arranged from A to Z for easy reference
*Seven subject areas covering all areas of biological chemistry
*Over 500 full-color articles of 4-9 pages each
*Over 1300 illustrations throughout with 800 in 4-color and over 200tables
*Glossary of specialized terms and 'Further Reading' section provided for every article
*Includes entries on the latest research techniques
*Appropriate for students, researchers, and professionals

Audience: Upper level college students, postdocs, and professionals in biochemistry, biophysics, cell biology, molecular biology, neuroscience, pharmacology, and oncology, academic and industrial libraries, and pharmaceutical companies.

Annotation Written for a broad, cross-disciplinary audience, theEncyclopedia of Biological Chemistryaddresses the fundamental discipline of biological chemistry underlying virtually all of the life sciences. This compilation of more than 500 different entries encompasses all aspects of biochemistry, as well as the extensions of this subject into the related fields of molecular biology, cell biology, genetics and biophysics. This comprehensive encyclopedia covers all areas of biological chemistry written by more than 500 selected international experts. Articles are generously illustrated including more than 800 images in four-color. Each entry contains a clear, concise review of the topic along with illustrations, a glossary of technical terms and a section for additional reading. Each entry further contains general background and term definitions as well as a comprehensive review of the current research in the field. Students, science journalists and scientists seeking a concise introduction to specific topics will appreciate the clear, tabular format of each entry. Also available online via ScienceDirect featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com. *Four-volume set with topics arranged from A to Z for easy reference *Seven subject areas covering all areas of biological chemistry *Over 500 full-color articles of 4-9 pages each *Over 1300 illustrations throughout with 800 in 4-color and over 200 tables *Glossary of specialized terms and 'Further Reading' section provided for every article *Includes entries on the latest research techniques *Appropriate for students, researchers, and professionals Written for a broad, cross-disciplinary audience, the Encyclopedia of Biological Chemistry addresses the fundamental discipline of biological chemistry underlying virtually all of the life sciences. This compilation of more than 500 different entries encompasses all aspects of biochemistry, as well as the extensions of this subject into the related fields of molecular biology, cell biology, genetics and biophysics. This comprehensive encyclopedia covers all areas of biological chemistry written by more than 500 selected international experts. Articles are generously illustrated including more than 800 images in four-color. Each entry contains a clear, concise review of the topic along with illustrations, a glossary of technical terms and a section for additional reading. Each entry further contains general background and term definitions as well as a comprehensive review of the current research in the field. Students, science journalists and scientists seeking a concise introduction to specific topics will appreciate the clear, tabular format of each entry.Also available online via ScienceDirect featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit (http://www.info.sciencedirect.com) www.info.sciencedirect.com .