Prosser David E, Jones Glenville
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Trends Biochem Sci. 2004 Dec;29(12):664-73. doi: 10.1016/j.tibs.2004.10.005.
Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vitamin D 25-hydroxylase that is involved in the first step of activation. The highly regulated, renal enzyme 25-hydroxyvitamin D-1alpha-hydroxylase contains the component CYP27B1, which completes the activation pathway to the hormonal form 1alpha,25-dihydroxyvitamin D(3). A five-step inactivation pathway from 1alpha,25-(OH)(2)D(3) to calcitroic acid is attributed to a single multifunctional CYP, CYP24A1, which is transcriptionally induced in vitamin D target cells by the action of 1alpha,25-(OH)(2)D(3). On the basis of alignments and crystal structures of other CYPs, homology models of vitamin-D-related CYPs have been generated. Two human forms of rickets caused by mutations of CYP2R1 and CYP27B1, as well as mouse knockout models of CYP27A1, CYP27B1 and CYP24A1, are helping us to establish the full in vivo physiological roles of the vitamin-D-related hydroxylases.
已证实六种细胞色素P450（CYP）同工型可使维生素D发生羟基化。其中四种，即CYP27A1、CYP2R1、CYP3A4和CYP2J3，是参与第一步激活反应的维生素D 25 - 羟化酶的候选酶。高度受调控的肾酶25 - 羟维生素D - 1α - 羟化酶含有CYP27B1成分，它可完成维生素D向激素形式1α,25 - 二羟维生素D（3）的激活途径。从1α,25 - （OH）2D（3）到钙三醇酸的五步失活途径归因于单一的多功能CYP，即CYP24A1，它在维生素D靶细胞中受1α,25 - （OH）2D（3）作用转录诱导产生。基于其他CYP的序列比对和晶体结构，已构建了与维生素D相关的CYP的同源模型。由CYP2R1和CYP27B1突变引起的两种人类佝偻病形式，以及CYP27A1、CYP27B1和CYP24A1的小鼠基因敲除模型，正帮助我们确定与维生素D相关的羟化酶在体内的完整生理作用。
