The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant todaytruly an essential publication for researchers in all fields of life sciences. - Human Genomics and Genetics - Structure and Mechanism - Regulation of Expression - Metabolism - Invertibrate P450s
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There has been significant progress in research in this area in recent years and current books on this subject are now out of date.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: 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.
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.
This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.
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.
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 BiologyTM 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.
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.
Cytochromes c are haemoproteins which carry out electron transfer in a wide variety of biological systems, necessitating different kinds of cytochrome c to fulfill different biological roles. The evolutionary relationship between cytochromes c and their host organisms are described, as well as their structural, spectroscopic and redox properties, including both electron-transfer rates and redox potentials. The treatment is aimed at the non-specialist so that both the techniques described and their application to cytochromes c can be understood. All classes of cytochrome c are dealt with to provide a comprehensive account of the field. No other text provides such a broad survey. Similar to the earlier volume "Cytochromes c: Biological Aspects" which deals with the classification, biosynthesis and biological role of cytochromes c, the present book is aimed at research workers and advanced students.
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
