Abstract

1. Nine forms of recombinant cytochrome P450 (P450 or CYP) enzymes were used to study roles of individual P450 enzymes in the oxidation of flavone and some other flavonoids, 4′-hydroxyflavone and 4′-, 3′-, and 2′-methoxyflavones, by human liver microsomes using LC-MS/MS analysis.

2. As has been reported previously , 4′-, 3′-, and 2′-methoxyflavones were preferentially O-demethylated by human liver P450 enzymes to form 4′-, 3′-, and 2′-hydroxylated flavones and also 3′,4′-dihydroxyflavone from the former two substrates.

3. In comparisons of product formation by oxidation of these methoxylated flavones, CYP2A6 was found to be a major enzyme catalysing flavone 4′- and 3′-hydroxylations by human liver microsomes but did not play significant roles in 2′-hydroxylation of flavone, O-demethylations of three methoxylated flavones, and the oxidation of 4′-hydroxyflavone to 3′,4′-dihydroxyflavone.

4. The effects of anti-CYP2A6 IgG and chemical P450 inhibitors suggested that different P450 enzymes, as well as CYP2A6, catalysed oxidation of these flavonoids at different positions by liver microsomes.

5. These studies suggest that CYP2A6 catalyses flavone 4′- and 3′-hydroxylations in human liver microsomes and that other P450 enzymes have different roles in oxidizing these flavonoids.

摘要

1. 九种形式的重组细胞色素 P450（P450 或 CYP）酶用于研究单个 P450 酶在黄酮和一些其他类黄酮、4'-羟基黄酮和 4 ' -、3'-和2'-甲氧基黄酮氧化中的作用，通过人肝微粒体使用 LC-MS/MS 分析。

2. 如前所述，4 ' -、3'-和2'-甲氧基黄酮优先被人肝 P450 酶O-去甲基化以形成 4 ' -、3'-和2'-羟基化黄酮以及 3' ， 4'-二羟基黄酮来自前两种底物。

3. 在比较这些甲氧基化黄酮氧化形成的产物时，发现 CYP2A6 是人肝微粒体催化黄酮 4'-和3'-羟基化的主要酶，但在黄酮、O-的2'-羟基化中没有显着作用。三种甲氧基化黄酮的去甲基化，以及 4'-羟基黄酮氧化成 3 ' ， 4'-二羟基黄酮。

4. 抗 CYP2A6 IgG 和化学 P450 抑制剂的作用表明，不同的 P450 酶以及 CYP2A6 在肝微粒体的不同位置催化这些黄酮类化合物的氧化。

5. 这些研究表明 CYP2A6 催化人肝微粒体中的黄酮 4 ' - 和 3 ' - 羟基化，并且其他 P450 酶在氧化这些黄酮类化合物中具有不同的作用。