Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase

Jorge H. Capdevila, Armando Karara, David J. Waxman, Martha V. Martin, J R Falck, F. Peter Guenguerich

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Abstract

Chiral analysis of the rat liver microsomal arachidonic acid epoxygenase metabolites shows enantioselective formation of 8,9-, 11,12-, and 14,15-cis-epoxyeicosatrienoic acids in an approximately 2:1, 4:1, and 2:1 ratio of antipodes, respectively. Animal treatment with the cytochrome P-450 inducer phenobarbital increased the overall enantiofacial selectivity of the microsomal epoxygenase and caused a concomitant inversion in the absolute configurations of its metabolites. These effects of phenobarbital were time-dependent and temporally linked to increases in the concentration of microsomal cytochrome P-450 enzymes. Reconstitution of the epoxygenase reaction utilizing several purified cytochromes P-450 demonstrated that the asymmetry of epoxidation is under cytochrome P-450 enzyme control. These results established that the chirality of the hepatic arachidonic acid epoxygenase is under regulatory control and confirm cytochromes P-450 IIB1 and IIB2 as two of the endogenous epoxygenases induced in vivo by phenobarbital.

Original languageEnglish (US)
Pages (from-to)10865-10871
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number19
StatePublished - Jul 5 1990

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Cytochrome P-450 Enzyme System
Phenobarbital
NSC 153174
Metabolites
Epoxidation
Chirality
Liver
Rats
Animals
Acids
arachidonate epoxygenase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Capdevila, J. H., Karara, A., Waxman, D. J., Martin, M. V., Falck, J. R., & Peter Guenguerich, F. (1990). Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. Journal of Biological Chemistry, 265(19), 10865-10871.

Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. / Capdevila, Jorge H.; Karara, Armando; Waxman, David J.; Martin, Martha V.; Falck, J R; Peter Guenguerich, F.

In: Journal of Biological Chemistry, Vol. 265, No. 19, 05.07.1990, p. 10865-10871.

Research output: Contribution to journalArticle

Capdevila, JH, Karara, A, Waxman, DJ, Martin, MV, Falck, JR & Peter Guenguerich, F 1990, 'Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase', Journal of Biological Chemistry, vol. 265, no. 19, pp. 10865-10871.
Capdevila, Jorge H. ; Karara, Armando ; Waxman, David J. ; Martin, Martha V. ; Falck, J R ; Peter Guenguerich, F. / Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 19. pp. 10865-10871.
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