Download or read book An Investigation of Interactions of Cytochrome B5 with Cytochrome P450s and Mechanisms of Cytochrome B5 on Cytochrome P450 Reactions written by Qiuxia Gao and published by . This book was released on 2007 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cytochromes P 450 and b5 written by David Cooper and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 550 pages. Available in PDF, EPUB and Kindle. Book excerpt: P-450 has in common with our nation that it can call Phila delphia its hometown. Yet there are differences, too. The U. S. A. was born and named in this city. P-450 was first recog nized here -- an odd CO-combining pigment without family or func tion. Japanese workers identified it as an unusual member of the cytochrome family. Finally, in Philadelphia, its biological func tion was established and its growth to a global power initiated. Since discovery of its function as terminal oxidase of the 21-steroid hydroxylase system of adrenocortical microsomes, P-450 has proved to play the same role in a wide variety of other mixed function oxidase systems involved in biosynthesis and catabolism of specific cell or body components as well as in the metabolism of foreign substances entering organisms. P-450-like oxygenating enzymes appear to be fundamental cellular constituents in most forms of aerobic organisms. Activation of molecular oxygen and incorporation of one of its atoms into organic compounds as cata lyzed by P-450 enzymes are reactions of vital importance not only for biosynthesis and degradation of steroid hormones necessary for sustaining life, but also for metabolic activation or inactivation of foreign agents such as drugs, food preservatives and additives, insecticides and carcinogens. Moreover, P-450 linked enzyme sys tems can either be induced or suppressed by these agents with significant biological consequences.
Download or read book Investigation of Surface Interactions Between Cytochrome B5 and Major Cytochrome P450 Isoforms written by Chunsheng Zhao and published by . This book was released on 2012 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytochrome b5 (cyt b5 or holo b5) is known as one of the key components in the microsomal cytochrome P450 (CYP) monooxygenase system that metabolizes structurally diverse endogenous and exogenous compounds. It has been reported to modulate many CYPs activity and the effect is both CYP isoform and substrate dependent. However, to date no consensus has been made on the underlying mechanism. In the present study, the surface interactions between cyt b5 and major hepatic CYP isoforms 3A4, 2C9, 2A6 and 2D6 were investigated. Chemical cross-linking coupled with mass spectrometric analysis was used to identify the potential electrostatic interactions on protein surfaces of cyt b5 and CYPs. Subsequently, the interaction models of cyt b5-CYPs were built using these identified cross-linking sites as constraints. For the first time, holo b5 and apo b5 (cyt b5 devoid of heme) surface interactions with CYPs were compared. The models suggest both of them bind to the same the groove on CYPs with very small difference in their orientations. The closest distances between the heme groups of cyt b5 and each CYP isoform are beyond direct electron transfer distance, indicating that cyt b5 likely modulates these CYP isoforms activity through allosteric effect in addition to the potential electron transfer role. In order to confirm that the residues involved in cross-linking are functionally important for cyt b5-CYP interaction, site-directed mutagenesis of CYP3A4 were carried out with the identified Lys residues on CYP3A4 being substituted with neutral residue Ala. In addition, the importance of Arg446 on CYP3A4 at the interface of the cyt b5-CYP3A4 complex model was also accessed by single-point mutation. Mutation of these residues reduced or abolished cyt b5 binding affinity, suggesting that electrostatic interactions on the interface of the two protein are functionally important and the chemical cross-linking coupled with mass spectrometric analysis serves as a useful tool to study protein-protein interaction.
Download or read book Guide to Cytochromes P450 written by David F. V. Lewis and published by CRC Press. This book was released on 2001-04-12 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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 level or in particular within the pharmaceutical industry. A Guide to Cytochrome P450 Structure and Function acts as an adjunct to the previous book Cytochromes P450: Structure, Function and Mechanism. It reviews the current status of the P450 field in terms of our present knowledge and understanding of the enzymes structure and function, including their multiplicity of forms, diversity of substrates, and selectivity. This is brought together with the latest research topics, including pharmacogenetics, regulation, human DMEs, toxicity screening and molecule modeling, to provide a fast-track approach for those new to the field.
Download or read book Guide to Cytochromes written by David F.V. Lewis and published by CRC Press. This book was released on 1996-07-03 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cytochromes written by David F.V. Lewis and published by Taylor & Francis. This book was released on 2003-09 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cytochrome P450 written by Paul R. Ortiz de Montellano and published by Springer. This book was released on 2015-03-13 with total page 912 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cytochromes P 450 and b5 written by David Cooper and published by Springer. This book was released on 1975-06-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: P-450 has in common with our nation that it can call Phila delphia its hometown. Yet there are differences, too. The U. S. A. was born and named in this city. P-450 was first recog nized here -- an odd CO-combining pigment without family or func tion. Japanese workers identified it as an unusual member of the cytochrome family. Finally, in Philadelphia, its biological func tion was established and its growth to a global power initiated. Since discovery of its function as terminal oxidase of the 21-steroid hydroxylase system of adrenocortical microsomes, P-450 has proved to play the same role in a wide variety of other mixed function oxidase systems involved in biosynthesis and catabolism of specific cell or body components as well as in the metabolism of foreign substances entering organisms. P-450-like oxygenating enzymes appear to be fundamental cellular constituents in most forms of aerobic organisms. Activation of molecular oxygen and incorporation of one of its atoms into organic compounds as cata lyzed by P-450 enzymes are reactions of vital importance not only for biosynthesis and degradation of steroid hormones necessary for sustaining life, but also for metabolic activation or inactivation of foreign agents such as drugs, food preservatives and additives, insecticides and carcinogens. Moreover, P-450 linked enzyme sys tems can either be induced or suppressed by these agents with significant biological consequences.
Download or read book Fifty Years of Cytochrome P450 Research written by Hiroshi Yamazaki and published by Springer. This book was released on 2014-06-23 with total page 403 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book encompasses major progress and future directions in cytochrome P450 (P450) research. Included are contributions by pioneers in the discovery of P450, with chapters on the molecular and functional properties of P450 and cutting-edge applications knowledge from various fields. P450 research has its roots in metabolism, but the true beginning was in 1962 with the publication by Tsuneo Omura and Ryo Sato in The Journal of Biological Chemistry on their discovery of the cytochrome. Following this groundbreaking study, over the last half-century, research has revealed that many forms of P450 exist in animals, plants and microorganisms. P450 research has expanded into many different fields including medicine, agriculture and biotechnology and has drawn the attention of industries for its bioengineering applications, such as drug development and creation of the “blue rose”. Also, research on nuclear receptors, which has grown out of research on the regulatory mechanisms of P450 genes, has become an important area in biology, medical science, pharmacology and clinical medicine—for example, with recent developments in personalized medicines. This book will draw readers into the important and exciting world of P450 and will encourage young students and scientists in P450 research to continue expanding the field via new approaches.
Download or read book Monooxygenase Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450 written by Eugene G. Hrycay and published by Springer. This book was released on 2015-05-22 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cytochrome P450 written by John B. Schenkman and published by Springer Science & Business Media. This book was released on 2013-03-08 with total page 740 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research written by M.R. Waterman and published by Springer Science & Business Media. This book was released on 2013-03-09 with total page 235 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cytochrome P450 Protocols written by Ian R. Phillips and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 473 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Cytochrome P450 Protocols, Ian Phillips and Elizabeth Shephard assemble a comprehensive collection of cutting-edge techniques for the investigation of cytochromes P450. Described in detail by hands-on experimentalists for easy reproducibility, these methods include spectral analysis, purification and enzymatic assays, expression in heterologous systems, and the production and use of antibodies, as well as methods for quantification of gene expression, transfection of hepatocytes, and for the investigation of DNA-protein interactions and genetic polymorphisms. In addition, because of the growing importance of in vitro systems in pharmacological toxicology, the book contains techniques for the culture of rodent and human hepatocytes and human epidermis. Cytochrome P450 induction as a biomarker for environmental pollution and the generation of mice with targeted gene disruptions complete this exhaustive collection of core techniques. Cytochrome P450 Protocols includes in one volume both state-of-the-art and classic methods that have not been superseded but remain extremely useful. The collection provides both novice and experienced researchers across many fields-toxicology, pharmacology, environmental biology, biochemistry, and molecular biology-all the tools needed to elucidate the crucial biological role played by cytochromes P450 in the metabolism of therapeutic drugs, chemical carcinogens, and environmental pollutants.
Download or read book Cytochromes P450 written by Costas Ioannides and published by Royal Society of Chemistry. This book was released on 2008-06-27 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cytochrome P450 written by John B. Schenkman and published by Springer. This book was released on 1993 with total page 784 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book the editors have brought together the widest group of investigators of the cytochrome P450 superfamily in order to present complete and right up-to-date coverage of this important enzyme system. The authors describe and analyze the components of the enzyme system, the reaction mechanisms involved, and the evolution and nomenclature of this superfamily of enzymes. They also describe the hepatic microsomal enzyme in a large number of species, from mammalian to birds and fish, to plants and unicellular organisms. The different P450 forms in different tissues of the mammalian system are also treated. Regulatory factors of P450 expression receive considerable attention, as do studies on the mechanism of interaction of the microsomal monooxygenase system components. Of particular interest to the reader are, for the first time, a compilation of chapters dedicated to forms of cytochrome P450 involved in steroid hormone biosynthesis. This volume presents the most complete survey of the cytochrome P450 field. It will allow recognition and understanding of the very wide implications this enzyme system has on life processes.
Download or read book Cytochromes P 450 and B5 written by David Cooper and published by . This book was released on 1975-06-01 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Drug Discovery and Evaluation Methods in Clinical Pharmacology written by H.Gerhard Vogel and published by Springer Science & Business Media. This book was released on 2010-12-15 with total page 576 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Discovery and Evaluation has become a more and more difficult, expensive and time-consuming process. The effect of a new compound has to be detected by in vitro and in vivo methods of pharmacology. The activity spectrum and the potency compared to existing drugs have to be determined. As these processes can be divided up stepwise we have designed a book series "Drug Discovery and Evaluation" in the form of a recommendation document. The methods to detect drug targets are described in the first volume of this series "Pharmacological Assays" comprising classical methods as well as new technologies. Before going to man, the most suitable compound has to be selected by pharmacokinetic studies and experiments in toxicology. These preclinical methods are described in the second volume „Safety and Pharmacokinetic Assays". Only then are first studies in human beings allowed. Special rules are established for Phase I studies. Clinical pharmacokinetics are performed in parallel with human studies on tolerability and therapeutic effects. Special studies according to various populations and different therapeutic indications are necessary. These items are covered in the third volume: „Methods in Clinical Pharmacology".
