Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially desaturates trans-retinol to 3,4-dehydroretinol
作者:Kevin M. Johnson、Thanh T.N. Phan、Matthew E. Albertolle、F. Peter Guengerich
DOI:10.1074/jbc.m116.773937
日期:2017.8
Recently, zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway. We show by proteomic analysis that P450 27C1 is localized to human skin, with two proteins of different sizes present, one being a cleavage
最近,斑马鱼和人类细胞色素P450(P450)27C1酶已被证明是类维生素A 3,4-去饱和酶。该酶在哺乳动物P450中是不常见的,因为主要的氧化反应是去饱和反应,而羟化反应只是一个次要途径。我们通过蛋白质组学分析显示P450 27C1定位于人类皮肤,存在两种不同大小的蛋白质,一种是全长形式的裂解产物。P450 27C1以100:3:2的比例将全反式视黄醇氧化为3,4-脱氢视黄醇,4-羟基(OH)视黄醇和3-OH视黄醇。3-OH和4-OH视黄醇都不是去饱和的中间体。在稳态下未观察到动力学爆发;底物结合速率和产物释放速率均不受限制。在存在底物的情况下,肾上腺素对铁的P450 27C1还原速度快了3倍,比总周转速度快了约5倍。用3,3-,4,4-和3,3,4,4-氘视黄醇观察到的动力学同位素效应为1.5-2.3(对kcat / Km)。由于代谢转换,C-4的氘化使3-羟基化增加4倍,而对4-羟