Activation of microsomal epoxide hydrolase by interaction with cytochromes p450: Kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function

K. I. Taura, H. Yamada, E. Naito, N. Ariyoshi, M. A. Mori, K. Oguri

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (KD) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable KD values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.

Original languageEnglish
Pages (from-to)275-280
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume402
Issue number2
DOIs
Publication statusPublished - Jun 15 2002
Externally publishedYes

Keywords

  • Benzo(a)pyrene-7,8-oxide
  • Cytochrome P450
  • Microsomal epoxide hydrolase
  • Protein-protein interaction
  • Styrene oxide
  • Surface plasmon resonance

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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