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

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

Research output: Contribution to journalArticle

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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 Km 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 - Mar 25 1993

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Epoxide Hydrolases
Epoxy Compounds
Hydration
Acids
Ethylene Oxide
NSC 153174
Regioselectivity
Enzymes
Cytosol
Metabolism
Liver
Lung
Substrates
Chemical analysis
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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.

Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. / Zeldin, Darryl C.; Kobayashi, Jun; Falck, John R.; Winder, Bruce S.; Hammock, Bruce D.; Snapper, James R.; Capdevila, Jorge H.

In: Journal of Biological Chemistry, Vol. 268, No. 9, 25.03.1993, p. 6402-6407.

Research output: Contribution to journalArticle

Zeldin, DC, Kobayashi, J, Falck, JR, Winder, BS, Hammock, BD, Snapper, JR & Capdevila, JH 1993, 'Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase', Journal of Biological Chemistry, vol. 268, no. 9, pp. 6402-6407.
Zeldin DC, Kobayashi J, Falck JR, Winder BS, Hammock BD, Snapper JR et al. Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. Journal of Biological Chemistry. 1993 Mar 25;268(9):6402-6407.
Zeldin, Darryl C. ; Kobayashi, Jun ; Falck, John R. ; Winder, Bruce S. ; Hammock, Bruce D. ; Snapper, James R. ; Capdevila, Jorge H. / Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 9. pp. 6402-6407.
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