TY - JOUR
T1 - NADPH-dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols
AU - Capdevila, Jorge H.
AU - Mosset, Paul
AU - Yadagiri, Pendri
AU - Lumin, Sun
AU - Falck, J. R.
N1 - Funding Information:
’ This work was supported by USPHS Grants GM 31278 and 33541 and the Robert A. Welch Foundation (I-782). ZThe chemical syntheses and spectral data of the oxygenated standards appear as a Miniprint Supplement. 3 To whom correspondence should be addressed. ’ Abbreviations used: EET, epoxyeicosatrienoic acid; DHET, vie-dihydroxyeicosatrienoic 5-OH-14,15-EET, 5-hydroxy-14,15-epoxy-6(E),8(2),
PY - 1988/2/15
Y1 - 1988/2/15
N2 - The arachidonic acid epoxygenase metabolite 14,15-epoxyeicosatrienoic acid is further metabolized by rat liver microsomal fractions to regioisomeric diepoxides and epoxyalcohols. Diepoxides result from epoxidation at the 5,6-, 8,9-, or 11,12-olefins. Hydroxylation leading to epoxyalcohols with a cis, trans-conjugated dienol occurs at carbons 5, 8, 9, or 12. Structural assignments were established by chromatographic and mass spectral comparisons with synthetic standards. The reaction requires NADPH and is inhibited by typical cytochrome P-450 inhibitors. Analysis of the time course of product formation during arachidonic acid oxidation by rat liver microsomal fractions indicated that all four regioisomeric epoxyeicosatrienoic acids can be further metabolized by the enzyme system.
AB - The arachidonic acid epoxygenase metabolite 14,15-epoxyeicosatrienoic acid is further metabolized by rat liver microsomal fractions to regioisomeric diepoxides and epoxyalcohols. Diepoxides result from epoxidation at the 5,6-, 8,9-, or 11,12-olefins. Hydroxylation leading to epoxyalcohols with a cis, trans-conjugated dienol occurs at carbons 5, 8, 9, or 12. Structural assignments were established by chromatographic and mass spectral comparisons with synthetic standards. The reaction requires NADPH and is inhibited by typical cytochrome P-450 inhibitors. Analysis of the time course of product formation during arachidonic acid oxidation by rat liver microsomal fractions indicated that all four regioisomeric epoxyeicosatrienoic acids can be further metabolized by the enzyme system.
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U2 - 10.1016/0003-9861(88)90111-7
DO - 10.1016/0003-9861(88)90111-7
M3 - Article
C2 - 3341770
AN - SCOPUS:0023882116
SN - 0003-9861
VL - 261
SP - 122
EP - 133
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -