Cytochrome P450 2E1: Its Role in Disease and Drug Metabolism

Cytochrome P450 2E1: Its Role in Disease and Drug Metabolism PDF

Author: Aparajita Dey

Publisher: Springer Science & Business Media

Published: 2013-02-12

Total Pages: 269

ISBN-13: 9400758812

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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.

Cytochromes P450

Cytochromes P450 PDF

Author: Costas Ioannides

Publisher: Royal Society of Chemistry

Published: 2008-06-27

Total Pages: 544

ISBN-13: 1847558429

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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There has been significant progress in research in this area in recent years and current books on this subject are now out of date.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.

Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer

Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer PDF

Author:

Publisher: Academic Press

Published: 2015-07-23

Total Pages: 506

ISBN-13: 0128031204

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Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer, the latest volume in the Advances in Pharmacology series, presents not only the function of cytochrome P450 but also its pharmacological roles in inflammation and cancer. Contains contributions from the best authors in the field Ideal reference for those conducting research in cancer, inflammation, cytochrome P450, metabolism, liver disease, and oxidative stress Provides an essential resource for pharmacologists, immunologists, and biochemists

Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0

Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0 PDF

Author: Patrick M. Dansette

Publisher: MDPI

Published: 2021-08-31

Total Pages: 286

ISBN-13: 3036502564

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This book, "Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity", presents five papers on human cytochrome P450 (CYP) and P450 reductase, three reviews on the role of CYPs in humans and their use as biomarkers, six papers on CYPs in microorganisms, and one study on CYP in insects. The first paper reports the in silico modeling of human CYP3A4 access channels. The second uses structural methods to explain the mechanism-based inactivation of CYP3A4 by mibefradil, 6,7-dihydroxy-bergamottin, and azamulin. The third article compares electron transfer in CYP2C9 and CYP2C19 using structural and biochemical methods, and the fourth uses kinetic methods to study electron transfer to CYP2C8 allelic mutants. The fifth article characterizes electron transfer between the reductase and CYP using in silico and in vitro methods, focusing on the conformations of the reductase. Then, two reviews describe clinical implications in cardiology and oncology and the role of fatty acid metabolism in cardiology and skin diseases. The second review is on the potential use of circulating extracellular vesicles as biomarkers. Five papers analyze the CYPomes of diverse microorganisms: the Bacillus genus, Mycobacteria, the fungi Tremellomycetes, Cyanobacteria, and Streptomyces. The sixth focuses on a specific Mycobacterium CYP, CYP128, and its importance in M. tuberculosis. The subject of the last paper is CYP in Sogatella furcifera, a plant pest, and its resistance to the insecticide sulfoxaflor.

Drug Metabolism in Diseases

Drug Metabolism in Diseases PDF

Author: Wen Xie

Publisher: Academic Press

Published: 2016-09-12

Total Pages: 294

ISBN-13: 0128029633

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Drug Metabolism in Diseases is a comprehensive reference devoted to the current state of research on the impact of various disease states on drug metabolism. The book contains valuable insights into mechanistic effects and examples of how to accurately predict drug metabolism during these different pathophysiological states. Each chapter clearly presents the effects of changes in drug metabolism and drug transporters on pharmacokinetics and disposition. This is a unique and useful approach for all those involved in drug discovery and development, and for clinicians and researchers in drug metabolism, pharmacology, and clinical pharmacology. Written and edited by leaders in drug metabolism from academia and industry Covers important topics, such as pharmacogenomics, drug metabolism in transplant patients, xenobiotic receptors, drug metabolism in geriatric and pediatric populations, and more Highlights topics of importance in drug discovery and development, and for safe and effective drug use in the clinic

Handbook of Pharmacogenomics and Stratified Medicine

Handbook of Pharmacogenomics and Stratified Medicine PDF

Author: Sandosh Padmanabhan

Publisher: Academic Press

Published: 2014-04-28

Total Pages: 1119

ISBN-13: 0123868831

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Handbook of Pharmacogenomics and Stratified Medicine is a comprehensive resource to understand this rapidly advancing field aiming to deliver the right drug at the right dose to the right patient at the right time. It is designed to provide a detailed, but accessible review of the entire field from basic principles to applications in various diseases. The chapters are written by international experts to allow readers from a wide variety of backgrounds, clinical and non-clinical (basic geneticists, pharmacologists, clinicians, trialists, industry personnel, ethicists) to understand the principles underpinning the progress in this area, the successes, failures and the challenges ahead. To be accessible to the widest range of readers, the clinical application section introduces the disease process, existing therapies, followed by pharmacogenomics and stratified medicine details. Medicine is the cornerstone of modern therapeutics prescribed on the basis that its benefit should outweigh its risk. It is well known that people respond differently to medications and in many cases the risk-benefit ratio for a particular drug may be a gray area. The last decade has seen a revolution in genomics both in terms of technological innovation and discovering genetic markers associated with disease. In parallel there has been steady progress in trying to make medicines safer and tailored to the individual. This has occurred across the whole spectrum of medicine, some more than others. In addition there is burgeoning interest from the pharmaceutical industry to leverage pharmacogenomics for more effective and efficient clinical drug development. Provides clinical and non-clinical researchers with practical information normally beyond their usual areas of research or expertise Includes an basic principles section explaining concepts of basic genetics, genetic epidemiology, bioinformatics, pharmacokinetics and pharmacodynamics Covers newer technologies– next generation sequencing, proteomics, metabolomics Provides information on animal models, lymphoblastoid cell lines, stem cells Provides detailed chapters on a wide range of disease conditions, implementation and regulatory issues Includes chapters on the global implications of pharmacogenomics

Cytochrome P450

Cytochrome P450 PDF

Author: Paul R. Ortiz de Montellano

Publisher: Springer Science & Business Media

Published: 2007-02-05

Total Pages: 702

ISBN-13: 0387274472

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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.

Drug Metabolism

Drug Metabolism PDF

Author: Mino R. Caira

Publisher: Springer Science & Business Media

Published: 2006-07-10

Total Pages: 431

ISBN-13: 140204142X

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Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

Transporters and Drug-Metabolizing Enzymes in Drug Toxicity

Transporters and Drug-Metabolizing Enzymes in Drug Toxicity PDF

Author: Albert P. Li

Publisher: John Wiley & Sons

Published: 2021-07-27

Total Pages: 530

ISBN-13: 1119170842

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TRANSPORTERS AND DRUG-METABOLIZING ENZYMES IN DRUG TOXICITY Explore up-to-date coverage on the interaction between drug metabolism enzymes, transporters, and drug toxicity with this leading resources Transporters and Drug-Metabolizing Enzymes in Drug Toxicity delivers a comprehensive and updated review of the relationship between drug metabolism, transporters, and toxicity, providing insights into a major challenge in drug development – accurate assessment of human drug toxicity. Combining two disciplines frequently considered independently of one another, the book combines drug metabolism and toxicology with a focus on the role of biotransformation on drug toxicity and as a major factor for species and individual differences. Mechanism and species differences in drug metabolizing enzymes and transporters are discussed, as are the methods used to investigate the role of drug metabolizing enzymes and transporters in drug toxicity. Finally, the distinguished authors describe promising new experimental approaches to accurately assessing human drug toxicity via the consideration of human-specific drug metabolism in toxicity assays. In addition to topics as diverse as extended clearance models, experimental approaches for the estimation of DILI potential of drug candidates and roles of transporters in renal drug toxicity, readers will also enjoy the inclusion of such subjects as: A thorough overview of and introduction to drug metabolism and transporters and drug toxicity An exploration of drug metabolism enzymes and transporter activities as risk factors of marketed drugs associated with drug-induced fatalities A discussion of human-based in vitro experimental models for the evaluation of metabolism-dependent drug toxicity A treatment of mechanism-based experimental models for the evaluation of BSEP inhibition and DILI An examination of transporters and cochlea toxicity Perfect for scientists, students, and practitioners with interests in metabolism, toxicology, and drug development in the pharmaceutical industry, Transporters and Drug-Metabolizing Enzymes in Drug Toxicity will also earn a place in the libraries of medicinal chemists, pharmacologists, biochemists, toxicologists, and regulators in the pharmaceutical and health industries.