Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase

Darryl C. Zeldin, Jun Kobayashi, J R Falck, Bruce S. Winder, Bruce D. Hammock, James R. Snapper, Jorge H. Capdevila

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

The hydration of cis-epoxyeicosatrienoic acids to the corresponding vic- dihydroxyeicosatrienoic acids by cytosolic epoxide hydrolase demonstrates moderate regioselectivity with rates of hydration highest for the 14,15- epoxide and lower for the 11,12- and 8,9-epoxide (4.5, 1.6, and 1.5 μmol of product/mg of protein/min, respectively). Incubations of the 8,9- and 14,15- epoxides with cytosolic epoxide hydrolase show stereoselective formation of diols (7:3 and 4:1 ratio of antipodes, respectively) and concomitant chiral enrichment of the remaining unmetabolized substrate. In contrast, hydration of the 11,12-epoxide is nonenantioselective. The K(m) value of the enzyme for the 14(R),15(S)-epoxide is 3 μM. Incubations of the enantiomerically pure 8,9- and 14,15-epoxides with lung or liver cytosol, followed by chiral analysis of the resulting diols demonstrate selective cleavage of the oxirane ring at C9 and C15, respectively. On the other hand, cleavage of the 11,12- oxirane ring was less selective. The stereochemical preference of the cytosolic epoxide hydrolase, together with the known chiral composition of the endogenous arachidonate epoxide pools, suggests a functional role for this enzyme in the metabolism of these important compounds.

Original languageEnglish (US)
Pages (from-to)6402-6407
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number9
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zeldin, D. C., Kobayashi, J., Falck, J. R., Winder, B. S., Hammock, B. D., Snapper, J. R., & Capdevila, J. H. (1993). Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. Journal of Biological Chemistry, 268(9), 6402-6407.