J. Biol. Chem., Vol. 261, Issue 14, 6332-6337, May, 1986
Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14- eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase
J Haeggstrom, J Meijer and O Radmark
Mouse liver homogenates transformed leukotriene A4 into a 5,6-dihydroxy-
7,9,11,14-eicosatetraenoic acid. This novel enzymatic metabolite of
leukotriene A4 was characterized by physical means including ultraviolet
spectroscopy, high performance liquid chromatography, and gas
chromatography-mass spectrometry. After subcellular fractionation, the
enzymatic activity was mostly recovered in the 105,000 X g supernatant and
20,000 X g pellet. Heat treatment (80 degrees C, 10 min) or digestion with
a proteolytic enzyme abolished the enzymatic activity in the high speed
supernatant. A purified cytosolic epoxide hydrolase from mouse liver also
transformed leukotriene A4 into a 5,6- dihydroxyeicosatetraenoic acid with
the same physico-chemical characteristics as the compound formed in crude
cytosol, but not into leukotriene B4, a compound previously reported to be
formed in liver cytosol (Haeggstrom, J., Radmark, O., and Fitzpatrick, F.A.
(1985) Biochim. Biophys. Acta 835, 378-384). These findings suggest a role
for leukotriene A4 as an endogenous substrate for cytosolic epoxide
hydrolase, an enzyme earlier characterized by xenobiotic substrates.
Furthermore, they indicate that leukotriene A4 hydrolase in liver cytosol
is a distinct enzyme, separate from previously described forms of epoxide
hydrolases in liver.