Metabolism of steroids by cytochrome P450 2C9 variants

被引：10

作者：

Uno, Tomohide ^{[1
]}

Nakano, Ryosuke ^{[1
]}

Kitagawa, Risa ^{[1
]}

Okada, Mai ^{[1
]}

Kanamaru, Kengo ^{[1
]}

Takenaka, Shinji ^{[2
]}

Uno, Yuichi ^{[3
]}

Imaishi, Hiromasa ^{[4
]}

机构：

[1] Kobe Univ, Fac Agr, Biol Chem, Nada Ku, Kobe, Hyogo, Japan

[2] Kobe Univ, Fac Agr, Environm Microbiol, Nada Ku, Kobe, Hyogo, Japan

[3] Kobe Univ, Fac Agr, Dept Plant Resource Sci, Nada Ku, Kobe, Hyogo, Japan

[4] Kobe Univ, Biosignal Res Ctr, Div Signal Responses, Lab Response Environm Mat,Nada Ku, Kobe, Hyogo, Japan

来源：

BIOPHARMACEUTICS & DRUG DISPOSITION | 2018年 / 39卷 / 08期

基金：

日本学术振兴会;

关键词：

CYP2C9; cytochrome P450; monooxygenase; polymorphism; steroid; VITRO FUNCTIONAL-CHARACTERIZATION; CYP2C9 ALLELIC VARIANTS; HUMAN LIVER-MICROSOMES; IN-VITRO; CHINESE POPULATION; AMINO-ACID; POLYMORPHISM; JAPANESE; P4502C9; 17-ALPHA-ETHINYLESTRADIOL;

D O I：

10.1002/bdd.2153

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild-type CYP2C9 and ten mutants were co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward steroids were examined. CYP2C9.2, CYP2C9.3, CYP2C9.4, CYP2C9.16, CYP2C9.28, CYP2C9.48 and CYP2C9.52 had higher testosterone 6-hydroxylation than CYP2C9.1. CYP2C9.4 showed higher progesterone 6-hydroxylation activity than CYP2C9.1. CYP2C9.28 and CYP2C9.48 showed higher progesterone 11-hydroxylation activity than CYP2C9.1. CYP2C9.48 showed higher progesterone 16-hydroxylation activity than CYP2C9.1. CYP2C9.2, CYP2C9.3, CYP2C9.16 and CYP2C9.30 had higher estrone 16-hydroxylation activity than CYP2C9.1. CYP2C9.3 had higher estrone 11-hydroxylation activity than CYP2C9.1. CYP2C9.39 and CYP2C9.57 showed similar activities to CYP2C9.1. These results indicate that the substrate specificity of CYP2C9.39 and CYP2C9.57 was not changed, but CYP2C9.2, CYP2C9.3, CYP2C9.4, CYP2C9.16, CYP2C9.28, CYP2C9.30, CYP2C9.48 and CYP2C9.52 showed different hydroxylation activities toward steroids compared with CYP2C9.1.

引用

页码：371 / 377

页数：7

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