Functional characterization of 20 allelic variants of CYP1A2

Miyabi Ito, Yuki Katono, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka

研究成果: Article査読

13 被引用数 (Scopus)

抄録

Genetic variations in cytochrome P450 1A2 (CYP1A2) are associated with interindividual variability in the metabolism and efficacy of many medications. Twenty CYP1A2 variants harboring amino acid substitutions were analyzed for functional changes in enzymatic activity. Recombinant CYP1A2 variant proteins were heterologously expressed in COS-7 cells. Enzyme kinetic analyses were performed with two representative CYP1A2 substrates, phenacetin and 7-ethoxyresorufin. Among the 20 CYP1A2 allelic variants, CYP1A2∗4, CYP1A2∗6, CYP1A2∗8, CYP1A2∗15, CYP1A2∗16, and CYP1A2∗21 were inactive toward both substrates. CYP1A2∗11 showed markedly reduced activity, but the changes in Km were different between the substrates. CYP1A2∗14 and CYP1A2∗20 exhibited increased activity compared to the wild-type enzyme, CYP1A2∗1. This comprehensive in vitro assessment provided insight into the specific metabolic activities of CYP1A2 proteins encoded by variant alleles, which may to be valuable when interpreting the results of in vivo studies.

本文言語English
ページ(範囲)247-252
ページ数6
ジャーナルDrug metabolism and pharmacokinetics
30
3
DOI
出版ステータスPublished - 2015 6月 1

ASJC Scopus subject areas

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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