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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.

Biomedicine. --- Biomedicine general. --- Medicine. --- Médecine --- Cytochrome P-450. --- Drugs -- Metabolism. --- Genetic regulation. --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Cytochromes --- Metalloenzymes --- Monooxygenases --- Health Workforce --- Biomedicine, general.

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Adrenal cortex --- Adrenocortical hormones --- Angiotensins --- Cytochrome P-450 --- #ABIB:aeco --- Adrenal cortex hormones --- Adrenal steroids --- Adrenocorticoids --- Corticoids --- Corticosteroids --- Steroid hormones --- Cytochromes --- Metalloenzymes --- Monooxygenases --- Angiotensin --- Neuropeptides --- Oligopeptides --- Peptide hormones --- Adrenal glands --- Hypothalamic-pituitary-adrenal axis --- Diseases --- Diagnosis --- Physiological effect --- Metabolism --- Conferences - Meetings

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This first volume in a projected series contains the proceedings of the first of the Keio University International Symposia for Life Sciences and Medicine under the sponsorship of the Keio University Medical Science Fund. As stated in the address by the President of Keio University at the opening of the 1996 symposium, the fund of Dr. Mitsunada Sakaguchi. The Keio was established by the generous donation University International Symposia for Life Sciences and Medicine constitute one of the core activities of the fund. The objective is to contribute to the international community by developing human resources, promoting scientific knowledge, and encouraging mutual exchange. Every year, the Executive Committee of the Interna­ tional Symposia for Life Sciences and Medicine selects the most interesting topics for the symposium from applications received in response to a call for papers to the Keio medical community. The publication of these proceedings is intended to publicize and distribute information arising from the lively discussions of the most exciting and current issues during the symposium. Weare grateful to Dr. Mitsunada Sakaguchi, who made the symposium possible, the members of the program committee, and the office staff whose support guaran­ teed the success of the symposium. Finally, we thank Springer-Verlag, Tokyo, for their assistance in publishing this work. Akimichi Kaneko, M. D. , Ph. D.

Human biochemistry --- Oxygen --- Homeostasis. --- Oxygenases. --- Cytochrome oxidase --- -Cytochrome P-450 --- -Oxygen --- -Respiration --- -Animal respiration --- Animals --- Breathing --- Ventilation (Physiology) --- Physiology --- Vital signs --- Aerobic exercises --- Breathing exercises --- Chalcogens --- Nonmetals --- Photosynthetic oxygen evolution --- Cytochromes --- Metalloenzymes --- Monooxygenases --- Cytochrome a3 --- Cytochrome c oxidase --- Indophenol oxidase --- Indophenolase --- Respiratory enzyme --- Warburg's respiratory enzyme --- Oxidoreductases --- Autoregulation --- metabolism. --- Congresses --- Metabolism --- -Congresses --- Respiration --- Cytochrome P-450 --- Homeostasis --- Oxygenases --- Congresses. --- metabolism --- congresses. --- -metabolism. --- Metabolism&delete& --- Oxygenase --- Neurosciences. --- Human physiology. --- Cell biology. --- Animal physiology. --- Human Physiology. --- Cell Biology. --- Animal Physiology. --- Cell biology --- Cellular biology --- Biology --- Cells --- Human biology --- Medical sciences --- Human body --- Neural sciences --- Neurological sciences --- Neuroscience --- Nervous system --- Animal physiology --- Anatomy --- Metabolism.

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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.

Antibiotics --- Bacillus --- biosynthetic gene clusters --- comparative analysis --- cytochrome P450 monooxygenase --- Mycobacterium --- P450 diversity percentage --- P450 profiling --- secondary metabolites --- NADPH-cytochrome P450 reductase (CPR) --- microsomal cytochrome P450 (CYP) --- Cytochrome b5 (CYB5) --- protein dynamics --- electron-transfer (ET) --- protein–protein interaction --- cytochromes P450 --- CYP3A4 --- active site access channels --- cavities boundaries --- minimal cost paths --- CYP139A1 --- genome data mining --- host metabolism --- Mycobacterium tuberculosis --- polyketides --- tuberculosis --- cryptococcus --- cryptococcus neoformans --- CYP51 --- fungal pathogens --- genome data-mining --- human pathogens --- CYP diversity analysis --- tremellomycetes --- trichosporon --- mechanism-based inhibitor --- crystal structure --- CYP4 genes --- genetic polymorphisms --- 20-HETE --- fatty acid --- arachidonic acid --- SNPs --- molecular functionality --- metabolism --- lamellar ichthyosis --- Bietti’s crystalline dystrophy --- cytochrome P450 --- isoform --- membrane protein --- protein-membrane interactions --- enzyme substrate specificity --- mutagenesis --- molecular dynamics simulation --- Sogatella furcifera --- sulfoxaflor --- transcriptome --- RNA interference --- CYP2C8 --- polymorphisms --- reactive oxygen species --- paclitaxel --- cytochrome P450 reductase --- electron transfer --- extracellular vesicles --- exosomes --- extrahepatic tissues --- plasma --- circulatory CYPs --- CYP450 --- drug metabolism --- precision Cardio-Oncology --- precision medicine --- systems medicine --- cytochromes P450 monooxygenases --- Cyanobacteria --- gene-cluster diversity percentage --- mathematical formula --- phylogenetic analysis --- Streptomyces --- cytochrome P450 monooxygenases --- terpenes --- P450 blooming --- non-ribosomal peptides --- cytochrome P450 monooxygenenases --- CYP128A1 --- Mycobacterium tuberculosis H37Rv --- molecular dynamic simulations --- azole drugs --- menaquinone

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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 the 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.

Cytochrome P-450 -- Metabolism. --- Cytochrome P-450 -- Toxicology. --- Xenobiotics -- Metabolism. --- Cytochrome P-450 CYP2E1 --- Fatty liver --- Metabolic Phenomena --- Stress, Physiological --- Aryl Hydrocarbon Hydroxylases --- Oxidoreductases, N-Demethylating --- Liver Diseases --- Cytochrome P-450 Enzyme System --- Phenomena and Processes --- Oxidoreductases Acting on CH-NH Group Donors --- Digestive System Diseases --- Physiological Processes --- Mixed Function Oxygenases --- Cytochromes --- Physiological Phenomena --- Diseases --- Oxidoreductases --- Oxygenases --- Enzymes --- Hemeproteins --- Enzymes and Coenzymes --- Proteins --- Chemicals and Drugs --- Amino Acids, Peptides, and Proteins --- Metabolism --- Oxidative Stress --- Fatty Liver --- Human Anatomy & Physiology --- Biology --- Health & Biological Sciences --- Pharmacy, Therapeutics, & Pharmacology --- Animal Biochemistry --- Cytology --- Toxicology --- Pathophysiology --- Cytochrome P-450. --- Medicine. --- Pharmacology. --- Life sciences. --- Biochemistry. --- Biomedicine. --- Pharmacology/Toxicology. --- Life Sciences, general. --- Biochemistry, general. --- Metalloenzymes --- Monooxygenases --- Toxicology. --- Biosciences --- Sciences, Life --- Science --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Chemistry --- Medical sciences --- Composition --- Drug effects --- Medical pharmacology --- Chemotherapy --- Drugs --- Pharmacy --- Physiological effect