Metabolism of steroids by cytochrome P450 2C9 variants.

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Uno T, Nakano R, Kitagawa R, Okada M, Kanamaru K, Takenaka S, Uno Y, Imaishi H

Metabolism of steroids by cytochrome P450 2C9 variants.

Biopharm Drug Dispos. 2018 Sep;39(8):371-377. doi: 10.1002/bdd.2153.

PubMed ID

30098040 [ View in PubMed

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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 6beta-hydroxylation than CYP2C9.1. CYP2C9.4 showed higher progesterone 6beta-hydroxylation activity than CYP2C9.1. CYP2C9.28 and CYP2C9.48 showed higher progesterone 11alpha-hydroxylation activity than CYP2C9.1. CYP2C9.48 showed higher progesterone 16alpha-hydroxylation activity than CYP2C9.1. CYP2C9.2, CYP2C9.3, CYP2C9.16 and CYP2C9.30 had higher estrone 16alpha-hydroxylation activity than CYP2C9.1. CYP2C9.3 had higher estrone 11alpha-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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Estrone	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details