Note: Intro -- Metal Ions in Life Sciences -- Historical Development and Perspectives of the Series -- Preface to Volume 3 -- Contents -- Contributors to Volume 3 -- Titles of Volumes 1-44 in the Metal Ions in Biological Systems Series -- Contents of Volumes in the Metal Ions in Life Sciences Series -- 1 Diversities and Similarities in P450 Systems: An Introduction -- 1. Oxygenases: Mediators of Biochemical Diversity -- 2. P450 Superfamily: Diversity at the Sequence Level -- 3. Diversity of P450 Structures: Folds and Conformations for Functions -- 4. Diversity in P450 Mechanisms -- 5. Diversity in Regulation Across the Superfamily -- 6. Diversity in the Evolution of Common Metabolic Functions -- 7. Summary and Outlook -- Acknowledgments -- Abbreviations -- References -- 2 Structural and Functional Mimics of Cytochromes P450 -- 1. Introduction -- 2. Iron Porphyrins Carrying a Thiolate or Modified Thiolate Ligand -- 3. Structurally Remote P450 Mimics -- 4. Concluding Remarks -- Acknowledgments -- Abbreviations -- References -- 3 Structures of P450 Proteins and Their Molecular Phylogeny -- 1. Introduction -- 2. P450 Evolution -- 3. P450 Families and Subfamilies -- 4. P450 Structures -- 5. Variation in P450 Function and Fold -- 6. Archaeon P450s -- 7. Summary and Conclusions -- Acknowledgments -- Abbreviations -- References -- 4 Aquatic P450 Species -- 1. Introduction. 'P450s Under the Surface' -- 2. Diversity of Aquatic Species -- 3. P450 Activities in Aquatic Invertebrates -- 4. Aquatic P450 Gene Families Identified -- 5. How Can We Use Information About P450s in Aquatic Species? -- 6. Conclusions and Outlook -- Acknowledgments -- Abbreviations -- References -- 5 The Electrochemistry of Cytochrome P450 -- 1. Introduction -- 2. Redox Titration (Potentiometric Equilibrium) Measurements -- 3. Voltammetric (Dynamic) Measurements -- 4. Conclusions. , Acknowledgments -- Abbreviations -- References -- 6 P450 Electron Transfer Reactions -- 1. Introduction -- 2. Catalytic Cycles -- 3. Electron Tunneling Wires -- 4. Concluding Remarks -- Acknowledgments -- Abbreviations -- References -- 7 Leakage in Cytochrome P450 Reactions in Relation to Protein Structural Properties -- 1. Introduction -- 2. Protein Structural Parameters -- 3. The Reaction Cycle of Cytochrome P450 -- 4. Protein Structural Parameters and Extent of Competitive Reactions -- 5. Concluding Remarks -- Acknowledgments -- Abbreviations -- References -- 8 Cytochromes P450 - Structural Basis for Binding and Catalysis -- 1. Introduction -- 2. Ligand Binding: Substrate Recognition and Access to the Distal Pocket -- 3. Architecture of the Active Site of CYP101 -- 4. The Distal Acid-Alcohol Pair -- 5. Experimental Characterization of Reaction Intermediates. Radiolysis as a Tool to Study Redox Reactions -- 6. Crystal Structures of Oxy-Ferrous Complexes -- 7. Mechanism: Summary, Conclusions, Speculations -- Acknowledgments -- Abbreviations -- References -- 9 Beyond Heme-Thiolate Interactions: Roles of the Secondary Coordination Sphere in Cytochrome P450 Systems -- 1. Overview of Cytochrome P450 Active Site Structure -- 2. Secondary Coordination Sphere on the Proximal Side -- 3. Secondary Coordination Sphere on the Distal Side -- 4. Summary and Outlook -- Acknowledgments -- Abbreviations -- References -- 10 Interactions of Cytochrome P450 with Nitric Oxide and Related Ligands -- 1. Introduction. Interactions of Ligands and Substrates with P450 Enzymes: General Features -- 2. Nitric Oxide and Its Interactions with P450S -- 3. Interactions of Imidazoles and Substituted Imidazoles with P450S -- 4. Other Ligands and Inhibitors of P450 Function -- 5. Conclusions and Future Prospects -- Acknowledgments -- Abbreviations -- References. , 11 Cytochrome P450-Catalyzed Hydroxylations and Epoxidations -- 1. Introduction -- 2. The Cytochrome P450 Enzymes -- 3. Three-Dimensional Structures of the Active Sites of Cytochrome P450 Enzymes -- 4. Role of the Cys Ligand: the Proximal Thiolate 'Push' and Distal Proton-Delivery -- 5. Multiple Mechanisms of P450 Catalysis -- 6. Multiple Oxidants in P450 Catalysis -- 7. Two States Theory -- 8. Influence of Substrate on the Spectral Properties and Reactivity of P450 Intermediates -- 9. Formation and Reactivity of Transient P450 Oxygen Intermediates -- 10. Summary and Future Prospective -- Acknowledgments -- Abbreviations -- References -- 12 Cytochrome P450 and Steroid Hormone Biosynthesis -- 1. Introduction -- 2. Steroidogenic P450s -- 3. Steroid Hormone Biosynthesis in the Adrenal Cortex -- 4. Steroid Hormone Biosynthesis in the Gonads -- 5. Extraadrenal and Extragonadal Steroidogenesis -- 6. Outlook for the Future -- Acknowledgments -- Abbreviations -- References -- 13 Carbon-Carbon Bond Cleavage by P450 Systems -- 1. Introduction -- 2. Cleavage Between Oxygenated Carbons -- 3. Cleavage Alpha to Oxygenated Carbons -- 4. Cleavage Alpha to Carbon Bearing Nitrogen -- 5. Carbon-Carbon Bond Cleavage Involving Peroxides -- 6. General Conclusions -- Acknowledgments -- Abbreviations -- References -- 14 Design and Engineering of Cytochrome P450 Systems -- 1. Introduction -- 2. Engineering Bacterial Cytochrome P450 Systems -- 3. Engineering Mammalian Cytochrome P450 Enzymes -- 4. Engineering Plant P450 Enzymes -- 5. Conclusions and Outlook -- Abbreviations -- References -- 15 Chemical Defense and Exploitation. Biotransformation of Xenobiotics by Cytochrome P450 Enzymes -- 1. Introduction. Chemical Defense -- 2. P450 Systems Involved in Chemical Defense -- 3. Common Themes -- 4. Industrial Applications of P450 Systems for Xenobiotic Decomposition. , 5. Conclusions and Future Prospects -- Acknowledgments -- Abbreviations -- References -- 16 Drug Metabolism as Catalyzed by Human Cytochrome P450 Systems -- 1. Introduction -- 2. Importance of P450 Enzymes in Drug Metabolism -- 3. Approaches to Predicting P450 Activity in Humans -- 4. P450s Involved in Drug Metabolism -- 5. Examples of Major Issues Involving Drug Metabolism by P450 -- 6. Summary -- Acknowledgments -- Abbreviations -- References -- 17 Cytochrome P450 Enzymes: Observations from the Clinic -- 1. Introduction -- 2. Drug Interactions -- 3. Drug Metabolism by Cytochrome P450 Enzymes -- 4. Alterations in P450 Enzymes -- 5. Active Transport of Drugs -- 6. Enzyme-Transporter Cooperativity -- 7. Use of Probes to Quantitate CYP Activity in Humans -- 8. Prodrugs -- 9. The Effect of Intravenous Versus Oral Administration on Drug Interactions -- 10. Additional Factors Affecting Drug Interactions -- 11. Herbal and Dietary Effects on CYP -- 12. Interactions with Commonly Used Medications -- 13. Beneficial Effects of Drug Interactions -- 14. FDA Regulations Regarding CYP450-Mediated Drug Interactions -- 15. Clinical Significance of Drug Interactions -- 16. Summary -- Acknowledgment -- Abbreviations -- References -- Subject Index.