1. The Halogens: Discovery, Occurrence, and Biochemistry of the Free Elements.- 1.1 Introduction.- 1.2 Fluorine.- 1.2.1 Isolation of Fluorine.- 1.2.2 Properties.- 1.2.3 Industrial Production and Uses of Fluorine.- 1.2.4 Biochemistry and Toxicology.- 1.3 Chlorine.- 1.3.1 Isolation of Chlorine.- 1.3.2 Properties.- 1.3.3 Industrial Production and Uses of Chlorine Gas.- 1.3.4 Biochemistry and Toxicology of Elemental Chlorine.- 1.3.5 Water Chlorination.- 1.4 Bromine.- 1.4.1 Isolation of Bromine.- 1.4.2 Industrial Production and Uses of Bromine.- 1.4.3 Biochemistry and Toxicology.- 1.5 Iodine.- 1.5.1 Isolation of Iodine.- 1.5.2 Industrial Production and Uses of Iodine.- 1.5.3 Biochemistry and Toxicology.- 1.6 Summary.- References.- 2. Biochemistry of Inorganic Fluoride.- 2.1 Introduction.- 2.2 Occurrence and Distribution of Inorganic Fluoride.- 2.3 Biological Uptake, Distribution, and Metabolism of Inorganic Fluoride.- 2.4 Overview of Effects of Fluoride on Enzyme Activity.- 2.5 Inhibition of 2-Phospho-D-Glycerate Hydrolase (Enolase).- 2.5.1 Properties of Enolase.- 2.5.2 Fluoride Inhibition of Enolase: Dependence on Inorganic Phosphate.- 2.5.3 Cation Requirements for Enolase.- 2.5.4 Interaction of Fluoride with Enzyme-Bound Metal.- 2.5.5 Synergistic Binding of Fluoride and Phosphate to the Enzyme–Metal Complex.- 2.5.6 Substrate-Dependent Inhibition of Yeast Enolase in the Absence of Pi.- 2.6 Inhibition of Inorganic Pyrophosphatase.- 2.6.1 Bakers’ Yeast Pyrophosphatase: Mg2+ and Substrate-Dependent Inhibition by Fluoride.- 2.6.2 Metal Binding Sites and Fluoride Inhibition.- 2.6.3 Biological Significance of Inhibition of Inorganic Pyrophosphatase by Fluoride.- 2.7 Inhibition of Acetylcholinesterases and Butyrylcholinesterase.- 2.8 Inhibition of (Na+ + K+)-Dependent ATPase (ATP Phosphohydrolase) by Fluoride—Influence of Aluminum.- 2.9 Stimulation of ATP Pyrophosphate-Lyase (Cyclizing) (Adenylate Cyclase).- 2.9.1 Mechanism of Hormonal Activation of Adenylate Cyclase.- 2.9.2 Effects of Fluoride on Adenylate Cyclase Activation and Deactivation.- 2.10 Stimulation of Photoreceptor Phosphodiesterase I by Fluoride.- 2.10.1 G-Proteins and the Visual Process.- 2.10.2 Effect of GTP and of Fluoride on Subunit Dissociation and on Tranducin GTPase Activity.- 2.10.3 Mechanism of Fluoride-Induced Activation of cGMP Phosphodiesterase.- 2.11 Stimulation of Polyphosphoinositide Phosphodiesterase by Fluoride.- 2.11.1 GTP Analogues and Fluoride Stimulate PPI-pde Activity.- 2.11.2 Cellular Effects of Fluoride and PPI-pde Stimulation.- 2.12 Additional Regulatory Proteins That Interact with Fluoride.- 2.13 Effects of Fluoride on Cellular Function.- 2.13.1 Effect of Fluoride on Platelet Function.- 2.13.2 Effect of Fluoride on Neutrophil Function.- 2.13.3 Effect of Fluoride on Protein Synthesis.- 2.14 In Vivo Toxicity of Fluoride.- 2.15 Effects of Fluoride on Mineralized Tissue.- 2.15.1 Introduction.- 2.15.2 Biochemistry of Mineralized Tissue—An Overview.- 2.15.3 Uptake of Fluoride by Bone.- 2.15.4 Fluorosis.- 2.15.5 Fluoride in the Treatment of Osteoporosis.- 2.15.6 Fluoride in Dental Tissue.- 2.16 Biochemistry of Inorganic Fluoride—Summary.- References.- 3. Biochemistry of Inorganic Chloride.- 3.1 Introduction.- 3.2 Transport of Chloride Through Cell Membranes.- 3.2.1 Transmembrane Transport Mechanisms.- 3.2.2 Classification of Chloride Transport Mechanisms.- 3.3 Chloride Transport and Body Fluid Homeostasis.- 3.4 Chloride/Bicarbonate Cotransport in Erythrocyte Membrane.- 3.4.1 General Properties of Erythrocyte Anion Transport.- 3.4.2 Kinetics of Transport.- 3.4.3 Molecular Probes for the Erythrocyte Cl-/HCO3- Transport System.- 3.4.4 The Structure of Band 3 and Models for Anion Transport.- 3.4.5 Band 3 and Chloride Transport—Summary.- 3.5 Chloride/Cation Cotransport and Cell Volume Control.- 3.6 Chloride and Transepithelial Transport.- 3.6.1 Transepithelial Transport.- 3.6.2 Chloride Transport and Renal Function.- 3.7 Epithelial Chloride Secretion and Cystic Fibrosis.- 3.7.1 Altered Electrolyte Transport in Cystic Fibrosis.- 3.7.2 Mechanism of Secretion in Airway Epithelia.- 3.7.3 Regulation of the Apical Chloride Channel and Cystic Fibrosis.- 3.7.4 Chloride Secretion and Cystic Fibrosis—Summary.- 3.8 Hydrochloric Acid Secretion in the Stomach.- 3.9 Glycine- and Gaba-Gated Chloride Channels.- 3.9.1 Chloride Channels and Neural Hyperpolarization.- 3.9.2 Identification of a GABA/Benzodiazepine Receptor–Chloride Ionophore Complex.- 3.9.3 Structure of the GABA/Benzodiazepine Receptor–Chloride Ionophore Complex.- 3.9.4 Physiological Relevance of Modulation of the GABA-Gated Chloride Channel.- 3.10 Stimulation and Inhibition of Enzymes by Chloride.- 3.10.1 Chloride and the Photosynthetic Formation of Oxygen.- 3.10.2 Activation of ?-Amylase.- 3.10.3 Inhibition of [Glu1]Plasminogen Activation.- 3.10.4 Stimulation of Angiotensin Converting Enzyme (ACE).- 3.10.5 Regulation of GTP-Dependent Regulatory Proteins by Chloride.- 3.11 Chloride and Neutrophil Function.- 3.11.1 Chloride Transport and Neutrophil Activation.- 3.11.2 Role of Chloride in the Microbicidal Action of Neutrophils.- 3.11.3 Chloride and the Pathogenesis of Inflammation.- 3.12 Biochemistry of Chloride—Summary.- References.- 4. Biochemistry of Inorganic Bromide.- 4.1 Introduction.- 4.2 Occurrence and Biodistribution of Bromide.- 4.3 Pharmacology and Toxicology of Bromide.- 4.3.1 Historical Background.- 4.3.2 “Bromism”—Chronic Bromide Toxicity.- 4.3.3 Effects of Bromide on the Central Nervous System.- 4.3.4 Bromide and Thyroid Function.- 4.4 Bromide and Anion Transport Mechanisms.- 4.4.1 Theoretical Basis for Anion Selectivity.- 4.4.2 Examples of Selectivity in Halide Transport.- 4.5 Inhibition and Stimulation of Enzymes by Bromide.- 4.6 Bromide and Eosinophil Function.- 4.6.1 Eosinophil Function and Host Defense.- 4.6.2 Brominating Oxidants from Human Eosinophils.- 4.6.3 Bromide and the Biological Production of Singlet Oxygen.- 4.7 Biochemistry of Bromide—Summary.- References.- 5. Biochemistry of Inorganic Iodide.- 5.1 Introduction.- 5.2 Occurrence, Uptake, and Biodistribution of Iodide.- 5.3 Iodide Transport into Thyroid and Other Iodide-Concentrating Tissues.- 5.3.1 The Thyroid Gland.- 5.3.2 The Iodide Pump.- 5.3.3 Regulation of Iodide Uptake: Thyroid-Stimulating Hormone (TSH).- 5.3.4 Autoregulation of Iodide Uptake.- 5.3.5 Additional Thyroid Ion Transport Mechanisms.- 5.3.6 Iodide Transport and Thyroglobulin Iodination.- 5.3.7 Additional Iodine-Concentrating Organs.- 5.4 Stimulation and Inhibition of Enzymes by Iodide.- 5.4.1 The Hofmeister Lyotropic Series and “Thyroid-Like” Systems.- 5.4.2 Carbonic Anhydrase Inhibition.- 5.4.3 Inhibition of Thyroid Adenylate Cyclase Activity.- 5.5 Biochemistry of Inorganic Iodide—Summary.- References.- 6. Iodotyrosine, Iodothyronines, and Thyroid Function.- 6.1 Iodotyrosine as a Biological Tracer.- 6.2 Iodothyronines and Thyroid Function.- 6.2.1 A Brief Historical Perspective.- 6.2.2 Biosynthesis of Thyroid Hormones.- 6.2.3 Release and Biological Transport of Thyroid Hormones.- 6.2.4 Thyroid Hormone Receptors and Biological Response.- 6.2.5 Regulation of Thyroid Hormone Synthesis and Release.- 6.2.6 Metabolism and Deactivation of Thyroid Hormones.- 6.2.7 Conclusion.- References.- 7. Biohalogenation.- 7.1 Introduction.- 7.2 Naturally Occurring Halometabolites.- 7.2.1 Chlorometabolites Produced by Fungi and Lichens.- 7.2.2 Halometabolites Produced by Bacteria.- 7.2.3 Halometabolites Produced by Marine Organisms.- 7.2.4 Halometabolites Produced by Higher Plants.- 7.2.5 Iodometabolites.- 7.2.6 Fluorometabolites.- 7.3 Haloperoxidases.- 7.3.1 Occurrence.- 7.3.2 Structure.- 7.3.3 Formation of the Halogenating Intermediate.- 7.3.4 The Halogenating Intermediate.- 7.3.5 Glycoprotein Structure and Reactivity.- 7.3.6 pH Dependence on Rates of Halogenation.- 7.3.7 Substrate Specificity and Scope of Reaction.- 7.4 Biosynthesis of Halometabolites in Marine Organisms.- 7.4.1 Acetogenin Biosynthesis.- 7.4.2 Terpene Biosynthesis.- 7.4.3 Formation of Mixed Halides.- 7.5 Biological Fluorination.- 7.6 Biohalogenation—Summary.- References.- 8. Persistent Polyhalogenated Compounds: Biochemistry, Toxicology, Medical Applications and Associated Environmental Issues.- 8.1 Introduction.- 8.2 Biochemistry and Toxicology of Chlorinated Insecticides.- 8.2.1 2,2-Bis (p-chlorophenyl)-1,1,1-trichloroethane (DDT) and Analogues.- 8.2.2 Chlorinated Cyclodiene, Hexachlorocyclohexane, and Polychloronorbornane Insecticides.- 8.3 Biochemistry and Toxicology of Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins, and Related Compounds.- 8.3.1 Industrial Applications of Halogenated Aromatic Compounds and the Environmental Consequences of Their Use.- 8.3.2 Toxic Manifestations of Halogenated Aromatic Hydrocarbons.- 8.3.3 The TCDD (Ah) Receptor and Enzyme Induction.- 8.3.4 The Aromatic Hydrocarbon (Ah) Receptor, AHH Induction, and TCDD Toxicity.- 8.3.5 Halogenated Aromatic Hydrocarbons and Thyroid Function.- 8.4 Medical Applications of Halogenated Hydrocarbons.- 8.4.1 Halogenated Volatile Anesthetics.- 8.4.2 Perfluorocarbons as Artificial Oxygen Transporters.- 8.5 Summary.- References.- 9. Metabolism of Halogenated Compounds—Biodehalogenation.- 9.1 Biodehalogenation—Introduction.- 9.1.1 Cytochrome P-450-Linked Monooxygenases.- 9.1.2 Glutathione S-Transferases.- 9.2 Metabolism of Halogenated Alkanes.- 9.2.1 Monooxygenase-Catalyzed Oxidations of Halogenated Alkanes.- 9.2.2 GSH-Dependent Metabolism of Haloalkanes.- 9.2.3 Metabolism of Environmentally Persistent Compounds Having Aliphatic Halogen–Carbon Bonds.- 9.3 Metabolism of Halogenated Alkenes.- 9.3.1 Vinyl Halides.- 9.3.2 1,1-Dichloroethylene (Vinylidene Chloride).- 9.3.3 cis- and trans-1,2-Dichloroethylene.- 9.3.4 Trichloroethylene.- 9.3.5 Tetrachloroethylene.- 9.3.6 Halogenated Allylic Compounds.- 9.4 GSH-Dependent Metabolism and Toxicity of Halogenated Alkenes.- 9.4.1 Renal ?-Lyase and Nephrotoxicity.- 9.4.2 Molecular Mechanism of ?-Lyase-Dependent Toxicity.- 9.4.3 Metabolism of Cyclodiene Insecticides.- 9.5 Metabolism of Halogenated Aromatic Compounds.- 9.5.1 Haloaromatic Compounds and the NIH Shift.- 9.5.2 Reductive Dehalogenation of Iodothyronines.- 9.5.3 Metabolism of Fluorinated Polycyclic Hydrocarbons—Modulation of Carcinogenicity.- 9.5.4 Metabolism of Environmentally Persistent Polyhalogenated Aromatic Compounds.- 9.6 Biodehalogenation Mediated by Microorganisms.- 9.7 Metabolism and Biodehalogenation—Summary.- References.