Functional characterization of 10 CYP4A11 allelic variants to evaluate the effect of genotype on arachidonic acid ω-hydroxylation

Takahiro Saito, Masashi Honda, Masamitsu Takahashi, Chiharu Tsukada, Miyabi Ito, Yuki Katono, Hiroki Hosono, Daisuke Saigusa, Naoto Suzuki, Yoshihisa Tomioka, Noriyasu Hirasawa, Masahiro Hiratsuka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Genetic variations in cytochrome P450 4A11 (CYP4A11) contributes to inter-individual variability in the metabolism of fatty acids such as arachidonic acid. CYP4A11 metabolizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which is important for the regulation of blood pressure. Polymorphisms in CYP4A11 are associated with susceptibility to hypertension. In this study, we evaluated the in vitro ω-hydroxylation of arachidonic acid by 10 CYP4A11 allelic variants, which cause amino acid substitutions in the encoded proteins. CYP4A11 variants were heterologously expressed in COS-7 cells and the kinetic parameters of arachidonic acid ω-hydroxylation were estimated. Among 10 CYP4A11 variants, 5 (CYP4A11-v1, CYP4A11-v2, CYP4A11-v3, CYP4A11-v4, and CYP4A11-v7) showed no or markedly lower activity compared to wild-type CYP4A11. This functional analysis of CYP4A11 variants could provide useful information for the effective prevention and treatment of hypertension.

Original languageEnglish
Pages (from-to)119-122
Number of pages4
JournalDrug metabolism and pharmacokinetics
Volume30
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • 20-HETE
  • Arachidonic acid
  • CYP4A11
  • Cytochrome P450
  • Genetic polymorphisms
  • Hypertension

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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