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The Second Edition reviews the impressive progress that has been made in the last ten years in cytochrome P450 research. Chapters emphasize structure, mechanism, biochemistry, and regulation. This edition offers expanded coverage of P450 crystal structures, site-specific mutagenesis as a probe of structure and function. New chapters explore the hormonal regulation of P450 enzymes, the cytochrome P450-catalyzed oxidation of eicosanoids, human P450 enzymes, and thiolate-ligated hemoproteins other than P450.
Cytochromes are coloured iron-containing proteins that transfer electrons during cellular respiration and photosynthesis. The Cytochrome P450 family of enzymes catalyze reactions whereby water-insoluble drugs or metabolites, that would otherwise reach toxic levels in cell membranes, are rendered suitably water-soluble to leave the cell and be excreted in the urine. Due to the extensive nature of this subject, which is an area of intense scientific interest, the field is rapidly advancing and there is a need for new textbooks to keep abreast of the latest developments. The book fulfils that role in providing a fast-track approach for those coming into the P450 field, either at postgraduate le...
With contributions by a team of internationally respected scientists, this book provides up-to-date information on the extensively studied cytochrome P450 enzyme in a very accessible manner.
Cytochromes P450: Metabolic and Toxicological Aspects examines cytochrome P450 proteins and their role in toxicity/carcinogenicity and the metabolism of foreign chemicals. Studying the function of these proteins enables us to: Predict the pathways and outcome of chemical metabolism to rationalize species, sex, and age differences in toxicity Anticipate drug interactions Modify doses to fit the needs of patients Contributions from internationally acknowledged experts are organized into three sections. The first section provides an overview, the next profiles each of the cytochrome P450 families and subfamilies involved in chemical metabolism, and the last section discusses new issues and developments of current interest. This detailed and thorough examination of cytochrome P450 will be a useful source for research scientists, especially those working in the pharmaceutical industry, dealing with the safety evaluation of chemicals and the study of their metabolism, pharmacokinetics, and toxicological properties.
This guide to the structure, function and mechanism of the cytochromes P450 focuses on the role of P450s in xenobiotic metabolism and toxicity. Colour illustrations show how modelling of P450s can rationalize their substrate specificity for the metabolism of both endogenous and exogenous chemicals.
This book covers the relevant aspects of cytochromes P450 for understanding their structure, function and mechanisms of action, such as physicochemical characterization methods, redox interactions, evolution and genetics, experimental and theoretical models, induction, inhibition and metabolism.
For this second edition of their much praised Cytochrome P450, the editors have collected accounts of the essential core techniques that use the latest methodologies for the investigation of P450s. Highlights include protocols for spectral analysis and purification of P450s, enzymatic assays of P450s and flavin-containing monooxygenases (FMOs), expression of P450s and FMOs in heterologous systems, and the production and use of antipeptide antibodies. Additional chapters contain readily reproducible techniques for the transfection of hepatocytes for gene regulation studies, P450 reporter gene assays, in situ hybridization, and analysis of genetic polymorphisms. Although the emphasis is on P450s of mammalian origin, many of the readily reproducible methods described are suitable for P450s from any source.
Helmut Sigel, Astrid Sigel and Roland K.O. Sigel, in close cooperation with John Wiley & Sons launch a new Series “Metal Ions in Life Sciences”. There exists a whole range of books on Cytochromes P450, but none with the focus of this volume. This new volume in the Series concentrates on current hot topics in the area and tries to work out the underlying common developments. As a result the reader will find a systematic account of new results in this exciting research area. The table of contents gives an idea on the wide span of chapters, starting with overviews and the presentation of specific systems, and ending with chapters on carbon-carbon bond cleavage by P450 sytems, drug metabolism as catalyzed by P450 systems, decomposition of xenobiotics by P450 enzymes and design and engineering of new P450 systems.
Metabolic research and especially that which focuses on the monooxygenase cytochrome P450 system has gone through dramatic progressive changes within the last decade. Availability of highly sophisticated analytical techniques has contributed to increased molecular understanding of biotransformation pathways. Nowadays designer drugs are computer composable focussing on metabolic stability. The rapid development of recombinant enzymes has, in many cases, replaced the intensive work on P450 isolation from naturally occurring sources. Recombinant P450s can be expressed in cell lines and thus made available for reproducible and constant use addressig a large number of scientific questions. This book describes the present position of such research.
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