Metabolism of steroids by cytochrome P450 2C9 variants |
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| Authors: | Tomohide Uno Ryosuke Nakano Risa Kitagawa Mai Okada Kengo Kanamaru Shinji Takenaka Yuichi Uno Hiromasa Imaishi |
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| Affiliation: | 1. Biological Chemistry, Faculty of Agriculture, Kobe University, Nada‐ku, Kobe, Hyogo, Japan;2. Environmental Microbiology, Faculty of Agriculture, Kobe University, Nada‐ku, Kobe, Hyogo, Japan;3. Department of Plant Resource Science, Faculty of Agriculture, Kobe University, Nada‐ku, Hyogo, Japan;4. Laboratory of Response to Environmental Materials, Division of Signal Responses, Biosignal Research Center, Kobe University, Nada‐ku, Kobe, Hyogo, Japan |
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| Abstract: | 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 6β‐hydroxylation than CYP2C9.1. CYP2C9.4 showed higher progesterone 6β‐hydroxylation activity than CYP2C9.1. CYP2C9.28 and CYP2C9.48 showed higher progesterone 11α‐hydroxylation activity than CYP2C9.1. CYP2C9.48 showed higher progesterone 16α‐hydroxylation activity than CYP2C9.1. CYP2C9.2, CYP2C9.3, CYP2C9.16 and CYP2C9.30 had higher estrone 16α‐hydroxylation activity than CYP2C9.1. CYP2C9.3 had higher estrone 11α‐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. |
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| Keywords: | CYP2C9 cytochrome P450 monooxygenase polymorphism steroid |
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