Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.
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 (Haeggström, J., Rådmark, 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.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D017572:Leukotriene A4; D008099:Liver / Q000201:enzymology*; D051379:Mice; D013237:Stereoisomerism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D017572:Leukotriene A4; C048698:5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid; D004851:Epoxide Hydrolases