Author: Paul Ortiz De Monetllano
Publisher: Springer Science & Business Media
ISBN: 9780306421471
Category : Computers
Languages : en
Pages : 572

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Book Description
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.

Author: Pavel Anzenbacher
Publisher: John Wiley & Sons
ISBN: 352732903X
Category : Medical
Languages : en
Pages : 755

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Book Description
A practice-oriented desktop reference for medical professionals, toxicologists and pharmaceutical researchers, this handbook provides systematic coverage of the metabolic pathways of all major classes of xenobiotics in the human body. The first part comprehensively reviews the main enzyme systems involved in biotransformation and how they are orchestrated in the body, while parts two to four cover the three main classes of xenobiotics: drugs, natural products, environmental pollutants. The part on drugs includes more than 300 substances from five major therapeutic groups (central nervous system, cardiovascular system, cancer, infection, and pain) as well as most drugs of abuse including nicotine, alcohol and "designer" drugs. Selected, well-documented case studies from the most important xenobiotics classes illustrate general principles of metabolism, making this equally useful for teaching courses on pharmacology, drug metabolism or molecular toxicology. Of particular interest, and unique to this volume is the inclusion of a wide range of additional xenobiotic compounds, including food supplements, herbal preparations, and agrochemicals.

Author: Osamu Hayaishi
Publisher: Elsevier
ISBN: 0323143261
Category : Science
Languages : en
Pages : 697

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Book Description
Molecular Mechanisms of Oxygen Activation reviews some of the major advances that have been made in our understanding of the molecular mechanisms underlying oxygen activation, with emphasis on the role of oxygen activation in contemporary biological processes. The biological role of oxygenases in the metabolism of fatty acids and steroids is discussed, along with the functions of heme-containing dioxygenases, a-ketoglutarate-coupled dioxygenases, and pterin-requiring aromatic amino acid hydroxylases. This book is comprised of 14 chapters and begins with an overview of the general properties and biological functions of oxygenases, along with the chemical aspects of oxygen fixation reactions. The reader is then introduced to research concerning fatty acid and steroid oxygenases which has appeared in the literature since 1962, paying particular attention to the mechanism of oxygenation and the biosynthesis and metabolism of steroids. Subsequent chapters explore the biological functions of a variety of oxygenases such as heme-containing dioxygenases, copper-containing oxygenases, flavoprotein oxygenases, and pterin-requiring aromatic amino acid hydroxylases. Superoxide dismutase, cytochrome c oxidase, peroxidase, and bacterial monoxygenases are also considered. This monograph should serve as a valuable reference for biochemists as well as undergraduate and graduate students of biochemistry.

Author: Paul R. Ortiz de Montellano
Publisher: Springer Science & Business Media
ISBN: 0387274472
Category : Medical
Languages : en
Pages : 702

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Book Description
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.

Author: Costas Ioannides
Publisher: Royal Society of Chemistry
ISBN: 1847558429
Category : Science
Languages : en
Pages : 538

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Book Description
During half a century, cytochrome P450 in its original uniqueness as an optically "wrong" cytochrome has attracted many investigators, who have contributed to the unveiling of a bewildering multiplicity of biologically important functions of the, by now very large, superfamily of cytochrome P 450 enzymes. With its discovery in 1958 and with the advent of more refined spectroscopic methodologies, through the double wavelength spectrophotometry, the mysterious enzyme system began to reveal its secrets in a swift stream of investigative successes. As one of the most extensively studied enzyme systems worldwide the interest in cytochromes P450 very much reflects its importance in the elimination of drugs and other chemicals from the body and its role in chemical toxicity and in the aetiology of diseases such as cancer. There has been significant progress in research in this area in recent years and current books on this subject are now out of date. This much needed, new, fully up-to-date publication fills this gap and emphasises the new relevant topics that have emerged during the last decade in an easily accessible manner. The enzyme system, cytochromes P450, comprises a number of families/subfamilies, and the focus of the book is to deal with each individually, furnishing information directly relevant to scientists involved in the development of chemicals, in particular in the evaluation of their safety. The book has contributions from internationally respected scientists who are research-active in the relevant areas. The authors have made extensive use of figures and tables so that the reader can access the necessary information without always having to read the text. In addition, a very extensive, user-friendly index is a unique hallmark of the book. Part A of this monograph introduces the reader to the current knowledge of the evolutionary development of cytochrome P450 structure and function. Furthermore, it deals with the role of this enzyme in the formation of reactive intermediates. The shrewd and extensive utilisation of the molecular biology methodology very rapidly led to a vast body of enzymes calling for a classification of the plethora of different cytochromes P450 (the superfamily) into families and subfamilies. This is aptly exemplified by the ten chapters in Part B of this book, dealing with ten subfamilies and two families of cytochrome P450. Part C offers an insight into another aspect of cytochrome P450 research, namely its regulation through receptor-mediated stimuli - as opposed to enzyme induction or inhibition. The final chapter translates the current data on one of several drug metabolising systems into clinical application and highlights the role of cytochromes P450 in the treatment of neoplastic growth. The book deals extensively with each family/subfamily of the cytochromes P450 that contribute to the metabolism of xenobiotics. Essential and invaluable information is provided for the industrial research scientist working with fine chemicals, and especially those in the pharmaceutical industry, dealing with the safety evaluation of chemicals or being involved in the study of their metabolism, pharmacokinetics and toxicological properties. It should also prove of interest to Regulators concerned with the safety evaluation of chemicals, research pharmacologists and toxicologists, and postgraduate students studying drug metabolism and toxicology at an advanced level.

Author: Eugene G. Hrycay
Publisher: Springer
ISBN: 3319160095
Category : Medical
Languages : en
Pages : 376

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Book Description
This book describes in 13 chapters mechanisms of P450 used to monooxygenate substrates via the NAD(P)H/O2 pathway using its peroxidase and peroxygenase functions. P450 also utilizes peroxides, peracids, periodate and iodosobenzene to oxygenate substrates via the shunt pathway. Also described are mechanisms used in the oxidation of pharmaceuticals by CYP3A4; acyl- carbon cleavage by CYP17A1, CYP19A1 and CYP51A1; metabolism of tetrabromodiphenyl ethers and bile acids by CYP2B6 and CYP3A4; metabolism of ω-6 and ω-3 polyunsaturated fatty acids; H2O2-mediated peroxygenation of substrates using substrate misrecognition; P450 oxidative reactions using electrochemical methods; electron transfer to P450 by redox proteins; hydroxylation of 1,8-cineole by P450cin; and peroxygenation by unspecific peroxygenases using H2O2. The topics covered are relevant to P450 researchers, professors and students from a variety of disciplines ranging from pharmacology, toxicology and microbiology to chemistry.

Author: A. I. Archakov
Publisher: CRC Press
ISBN:
Category : Nature
Languages : en
Pages : 356

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Book Description
A critical review of the more significant achievements in a relatively new research field that is concerned with enzyme systems involved in the activation of molecular oxygen, primarily the major oxygenase systems containing cytochrome P-450."

Author: Ramón Cacabelos
Publisher: Academic Press
ISBN: 0128139404
Category : Medical
Languages : en
Pages : 986

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Book Description
Pharmacoepigenetics provides a comprehensive volume on the role of epigenetics and epigenomics in drug discovery and development, providing a detailed, but accessible, view of the field, from basic principles, to applications in disease therapeutics. Leading international researchers from across academia, clinical settings and the pharmaceutical industry discuss the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, and treatment, current epigenetic drugs, and the application of epigenetic procedures in drug development. Throughout the book, chapter authors offer a balanced and objective discussion of the future of pharmacoepigenetics and its crucial contribution to the growth of precision and personalized medicine. - Fully examines the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, treatment, current epigenetic drugs and the application of epigenetic procedures in drug development - Features chapter contributions from leading international researchers in academia, clinical settings and the pharmaceutical industry - Instructs researchers, students and clinicians on how to better interpret and employ pharmacoepigenetics in drug development, efficiency and safety - Provides a balanced and objective discussion of the future of pharmacoepigenetics and its crucial role in precision medicine

Author: Aparajita Dey
Publisher: Springer Science & Business Media
ISBN: 9400758812
Category : Medical
Languages : en
Pages : 269

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Book Description
The book deals with various clinical aspects of cytochrome P450 2E1 (CYP2E1) which is a potent source for oxidative stress. Oxidative stress is critical for pathogenesis of diseases and CYP2E1 is a major contributor for oxidative stress. Several clinical disorders are associated with changes in regulation of CYP2E1 and the consequent abnormalities which include alcoholic liver disease, alcoholic pancreatitis, carcinogenesis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, obesity, hepatitis C virus infection, reproductive organ toxicity, hepatocellular and cholestatic liver cirrhosis, inhibition of bone repair, cross-tolerance in smokers and people treated with nicotine, disorders of central nervous system, changes in metabolism of protoxicants in the circulatory system and susceptibility to human papillomavirus infection. Hence, CYP2E1 emerges as a new and potent player in aggravating injury and furthering disease complications.

Author: John B. Schenkman
Publisher: Springer Science & Business Media
ISBN: 3642777635
Category : Medical
Languages : en
Pages : 740

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Book Description
The most complete and up-to-date survey of this important superfamily of enzymes, including the first ever coverage of the forms involved in steroid hormone biosynthesis. The components of the enzyme system, the reaction mechanisms involved, and the evolution and nomenclature are analyzed, as is the hepatic microsomal enzyme in a large number of species, illustrating the very wide implications for life processes.