Regulation of Cytochrome P450 Enzymes by Reversible Oxidation of Thiols to Sulfenic Acids
作者单位：Department of BiochemistryVanderbilt University School of Medicine
会议名称：《中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议》
会议日期：2018年
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术]
基 金：Supported in part by United States NIH grant R01 GM118122
关 键 词：Cytochrome P450 redox control sulfenic acid drug metabolism steroidogenesis heme ligands
摘 要：Cytochrome P450(P450) enzymes are the major catalysts involved in the metabolism of drugs,steroids,chemical carcinogens,and fat-soluble *** they are involved in 95% of oxidation/reduction reactions of *** signature spectroscopic properties and the catalytic activities are related to a conserved cysteine thiolate ligand binding to the proximal side of the heme *** found that the activity of one human P450 enzyme,P450 4 A11,was stimulated by the addition of mild reducing agents,***,and attenuated by H2 *** analyzed the enzyme and did not find disulfides but did find that the cysteine sulfur was oxidized to a sulfenic acid(-SOH),a reversible *** then found numerous drug metabolizing enzymes that contained sulfenic acids,including several mouse and human P450 s with the heme-cysteinyl sulfenic *** sulfenic acid was found in mouse and human liver and kidney samples in situ,suggesting physiological *** dynamics simulations suggest roles for specific amino acids in modulating the oxidation of the *** part of our continuing efforts in characterization of these systems in cells,we have synthesized new heavy isotope-labeled reagents with much faster kinetics than dimedone and iodoacetamide,which can be used to label sulfenic acids and disulfides,using liquid chromatography-mass *** phenomenon represents a potential new means of post-transcriptionally regulating the activities of P450 enzymes,although more in vivo evidence is in order.