Major advances have been made in recent years in clarifying the molecular properties of the cytochrome P-450 system. These advances stem, in practical terms, from the generally recognized importance of cytochrome P-450 in the metabolism of drugs and in the bioactivation of xenobiotics to toxic products. The fascinating multiplicity and differential regulation of cytochrome P-450 isozymes, and their ability to catalyze extraordinarily difficult chemical transformations, have independently drawn many chemists and biochemists into the P-450 circle. Progress in the field, from a technical point of view, has been propelled by the de- velopment of reliable procedures for the purification of membrane-bound enzymes, by the growing repertoire of molecular biological techniques, and by the development of chemical models that mimic the catalytic action of P-450. As a result, our understanding of the P-450 system is moving from the descriptive, pharmacological level into the tangible realm of atomic detail.
The rapid progress and multidisciplinary character of the cytochrome P-450 field, which cuts across the lines that traditionally divide disciplines as diverse as inorganic chemistry and genetics, have created a need for an up-to-date evaluation of the advances that have been made. It is hoped that this book, with its molecular focus on the cytochrome P-450 system, will alleviate this need. The authors of the individual chapters have strived to emphasize recent results without sacrificing the background required to make their chapters comprehensible to informed nonspecialists.
1. Metalloporphyrin Models for Cytochrome P-450.- 2. Comparison of the Peroxidase Activity of Hemeproteins and Cytochrome P-450.- 3. The Topology of the Mammalian Cytochrome P-450 Active Site.- 4. Cytochrome P-450 Reductase and Cytochrome b5 in Cytochrome P-450 Catalysis.- 5. Cytochrome P-450 Organization and Membrane Interactions.- 6. Comparative Structures of P-450 Cytochromes.- 7. Oxygen Activation and Transfer.- 8. Inhibition of Cytochrome P-450 Enzymes.- 9. Induction of Hepatic P-450 Isozymes: Evidence for Specific Receptors.- 10. Regulation of Synthesis and Activity of Cytochrome P-450 Enzymes in Physiological Pathways.- 11. Cytochrome P-450 Enzymes in Sterol Biosynthesis and Metabolism.- 12. Cytochrome P450cam and Other Bacterial P-450 Enzymes.- 13. The Crystal Structure of Cytochrome P450cam.- Appendix. Rat Hepatic Cytochrome P-450: Comparative Study of Multiple Isozymic Forms.