The mechanism of inhibition of cytochrome P450IIE1 by dihydrocapsaicin

Peter M. Gannett, Patrick Iversen, Terence Lawson

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Dihydrocapsaicin (2) is a noncompetitive inhibitor of cytochrome P450IIE1. This was demonstrated by studying the inhibition of p-nitrophenol oxidation. The covalent binding of 2 to cytochrome P450IIE1 was examined by incubating tritiated 2 with rat liver microsomes and gel electrophoresis of the resulting bound cytochrome P450 isozymes. Autoradiograms of these gels displayed a single band at approximately 48 kDa. The mechanism whereby 2 became covalently bonded to cytochrome P450IIE1 was explored by studying the oxidation of 2 by electrochemical, chemical, and enzymatic methods. Oxidation of 2 by all methods generally resulted in the formation of the 5,5′-dimer of 2, 4, which likely forms by dimerization of the phenoxy radical 7. It is suggested that 2 is oxidized to 7 by cytochrome P450IIE1 and 7 then covalently bonds to cytochrome P450IIE1 thereby inactivating it.

Original languageEnglish (US)
Pages (from-to)185-198
Number of pages14
JournalBioorganic Chemistry
Volume18
Issue number2
DOIs
Publication statusPublished - Jun 1990

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this