Paul R. Ortiz De Montellano - Böcker

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.

Cytochrome P450: Structure, Mechanism, and Biochemistry, third edition is a revision of a review that summarizes the current state of research in the field of drug metabolism. The emphasis is on structure, mechanism, biochemistry, and regulation. Coverage is interdisciplinary, ranging from bioinorganic chemistry of cytochrome P450 to its relevance in human medicine. Each chapter provides an in-depth review of a given topic, but concentrates on advances of the last 10 years.

Also included are chapters on cytochrome P450 reductase (the redox partner of CYPs) and the flavin-containing monooxygenases (FMOs), and metabolomic and lipidomic approaches for identification of endogenous substrates of CYPs (‘de-orphanizing’ CYP substrates).

Cytochromes P450 (CYPs) comprise a large superfamily of proteins that are of central importance in the detoxification or activation of a tremendous number of natural and synthetic hydrophobic xenobiotics, including many therapeutic drugs, chemical carcinogens and environmental pollutants. CYPs are important in mediating interactions between an organism and its chemical environment and in the regulation of physiological processes. Cytochrome P450 Protocols, Third Edition focuses on high-throughput methods for the simultaneous analysis of multiple CYPs, substrates or ligands. Although the emphasis is on CYPs of mammalian origin, it reflects an increasing interest in CYPs of bacterial species. Also included are chapters on cytochrome P450 reductase (the redox partner of CYPs) and the flavin-containing monooxygenases (FMOs), and metabolomic and lipidomic approaches for identification of endogenous substrates of CYPs (‘de-orphanizing’ CYP substrates). Written in the successful Methods in Molecular Biology™ series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Cytochrome P450 Protocols, Third Edition provides a wide range of techniques accessible to researchers in fields as diverse as biochemistry, molecular biology, pharmacology, toxicology, environmental biology and genetics.

This authoritative Fourth Edition summarizes the advances of the past decade concerning the structure, mechanism, and biochemistry of cytochrome P450 enzymes, with sufficient coverage of earlier work to make each chapter a comprehensive review of the field. Thirteen chapters are divided into two detailed volumes, the first covering the fundamentals of cytochrome P450 biochemistry, as well as the microbial, plant, and insect systems, and the second exclusively focusing on mammalian systems.Volume 1 begins with an exploration of the biophysics and mechanistic enzymology of cytochrome P450 enzymes, with a discussion of the structures of P450 enzymes and their electron donor partners, the mechanisms of oxygen activation and substrate oxidation, and the approaches and nature of cytochrome P450 inhibition. Two more chapters discuss the nature and roles of cytochrome P450 enzymes in microbes, plants and insects, and an eighth chapter is a survey of the potential utility of P450 enzymes in biotechnology. The first chapter of Volume 2 examines the roles of P450 enzymes in mammals, mainly humans. Four further chapters then deal with the genetic and hormonal regulation of P450 enzymes and their specific roles in the processing of sterols and lipids. Cytochrome P450: Structure, Mechanism, and Biochemistry is a key resource for scientists, professors, and students interested in fields as diverse as biochemistry, chemistry, biophysics, molecular biology, pharmacology and toxicology.