Roles of cytochrome P450 2A6 in the oxidation of flavone, 4'-hydroxyflavone, and 4'-, 3'-, and 2'-methoxyflavones by human liver microsomes.
Roles of cytochrome P450 2A6 in the oxidation of flavone, 4'-hydroxyflavone, and 4'-, 3'-, and 2'-methoxyflavones by human liver microsomes.
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DOI：
10.1080/00498254.2021.1950866
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Shimada T
中科院分区：
文献类型：
--
作者：
Nagayoshi H;Murayama N;Takenaka S;Kim V;Kim D;Komori M;Yamazaki H;Guengerich FP;Shimada T
采用LC-MS/MS分析方法，研究了9种重组细胞色素P450酶（P450或CYP 1A 1）在人肝微粒体氧化黄酮和其他黄酮类化合物（4 ′-羟基黄酮和4 ′-、3 ′-和2 ′-甲氧基黄酮）中的作用。如先前所报道的（Nagayoshi等人，Xenobiotica 50，1158-1169，2020），4 ′-、3 ′-和2 ′-甲氧基黄酮优先被人肝P450酶O-脱甲基化，形成4 ′-、3 ′-和2 ′-羟基化黄酮，以及来自前两种底物的3 ′，4 ′-二羟基黄酮。在这些甲氧基化黄酮氧化产物形成的比较中，发现CYP 2A 6是催化人肝微粒体黄酮4 ′-和3 ′-羟基化的主要酶，但在黄酮的2 ′-羟基化、三种甲氧基化黄酮的O-去甲基化和4 ′-羟基黄酮氧化为3 ′，4 ′-二羟基黄酮中没有发挥重要作用。抗CYP 2A 6 IgG和化学P450抑制剂的作用表明，不同的P450酶，以及CYP 2A 6，催化氧化这些黄酮类化合物在不同位置的肝微粒体。这些研究表明，CYP 2A 6催化人肝微粒体中黄酮4 ′-和3 ′-羟基化，其他P450酶在氧化这些黄酮类化合物中具有不同的作用。
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. As has been reported previously (Nagayoshi et al., Xenobiotica 50, 1158-1169, 2020), 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. In comparisons of product formation by oxidation of these methoxylated flavones, CYP2A6 was found to be a major enzyme catalyzing 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. The effects of anti-CYP2A6 IgG and chemical P450 inhibitors suggested that different P450 enzymes, as well as CYP2A6, catalyzed oxidation of these flavonoids at different positions by liver microsomes. These studies suggest that CYP2A6 catalyzes flavone 4´- and 3´-hydroxylations in human liver microsomes and that other P450 enzymes have different roles in oxidizing these flavonoids.
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影响因子：
3.7
作者：
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DOI：
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