Le Quesne P W, Abdel-Baky S, Durga A V, Purdy R H
Biochemistry. 1986 Apr 22;25(8):2065-72. doi: 10.1021/bi00356a035.
A mechanism is proposed for mixed-function oxidase-catalyzed formation of the catechol estrogens 2-hydroxy- and 4-hydroxyestradiol from estradiol. This mechanism involves nonaromatic epoxyenones as intermediates. The isomeric 1 alpha,2 alpha-epoxy-17 beta-hydroxyestr-4-en-3-one and 1 beta,2 beta-epoxy-17 beta-hydroxyestr-4-en-3-one (the latter as its 17-acetate) were synthesized from 17 beta-hydroxy-5 alpha-estran-3-one. The isomeric 4 alpha,5 alpha-epoxy-17 beta-hydroxyestr-1-en-3-one and 4 beta,5 beta-epoxy-17 beta-hydroxyestr-1-en-3-one were prepared from 19-nortestosterone. From incubations of [6,7-3H]estradiol with microsomes from MCF-7 human breast cancer cells, which principally catalyze the formation of 2-hydroxyestradiol from estradiol, we were able to isolate a 3H-labeled product with the chromatographic properties of 1 beta, 2 beta-epoxy-17 beta-hydroxyestr-4-en-3-one (as its 17-acetate). The soluble protein fraction of homogenates of rat liver, which is devoid of estrogen 2-/4-hydroxylase activity, has been shown to catalyze the formation of 2- and 4-hydroxyestradiol from the 1 alpha,2 alpha-epoxide and from the 4 alpha,5 alpha- and 4 beta,5 beta-epoxides, respectively. We suggest that these results taken together strongly support a role for epoxyenones as intermediates in the formation of catechol estrogens.
本文提出了一种混合功能氧化酶催化雌二醇生成儿茶酚雌激素2-羟基雌二醇和4-羟基雌二醇的机制。该机制涉及非芳香族环氧烯酮作为中间体。由17β-羟基-5α-雌烷-3-酮合成了异构体1α,2α-环氧-17β-羟基雌-4-烯-3-酮和1β,2β-环氧-17β-羟基雌-4-烯-3-酮（后者为其17-乙酸酯）。由19-去甲睾酮制备了异构体4α,5α-环氧-17β-羟基雌-1-烯-3-酮和4β,5β-环氧-17β-羟基雌-1-烯-3-酮。用[6,7-³H]雌二醇与MCF-7人乳腺癌细胞微粒体进行孵育，该微粒体主要催化雌二醇生成2-羟基雌二醇，我们能够分离出一种具有1β,2β-环氧-17β-羟基雌-4-烯-3-酮（作为其17-乙酸酯）色谱特性的³H标记产物。大鼠肝脏匀浆的可溶性蛋白部分缺乏雌激素2-/4-羟化酶活性，已证明其分别催化1α,2α-环氧化物以及4α,5α-和4β,5β-环氧化物生成2-羟基雌二醇和4-羟基雌二醇。我们认为，综合这些结果有力地支持了环氧烯酮作为儿茶酚雌激素形成过程中的中间体的作用。
