Novel biological transformations of 15-Ls-hydroperoxy-5,8,11,13-eicosatetraenoic acid.
[1-14C]Arachidonic acid was incubated with homogenates of the fungus, Saprolegnia parasitica. The products consisted of comparable amounts of two epoxy alcohols, 15-Ls-hydroxy-11,12-epoxy-5cis,8cis,13trans- eicosatrienoic acid and 15-hydroxy-13,14-epoxy-5cis,8cis,11cis-eicosatrienoic acid. Results of incubations carried out in the presence of nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid, p-hydroxymercuribenzoate as well as glutathione peroxidase plus reduced glutathione demonstrated that transformation of arachidonic acid into epoxy alcohols occurred with the formation of 15-Ls-hydroperoxy-5cis,8cis,11cis,13trans- eicosatetraenoic acid (15-HPETE) as an intermediate. The pathway involved a lipoxygenase catalyzing the oxygenation of arachidonic acid at the 15L position to produce 15-HPETE, and a hydroperoxide isomerase activity which catalyzed conversion of 15-HPETE into the two epoxy alcohols. Studies with 15-[18O2]HPETE demonstrated that both oxygens of 15-HPETE were retained in the epoxy alcohols. Furthermore, experiments with mixtures of 15-[18O2]-and 15-[16O2]HPETE showed that conversion of 15-HPETE into epoxy alcohols occurred by an intramolecular transfer of hydroperoxide oxygen.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D005658:Fungi / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000378:metabolism*; D010103:Oxygen Isotopes; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D006902:Hydroxymercuribenzoates; D015289:Leukotrienes; D008054:Lipid Peroxides; D010103:Oxygen Isotopes; C030601:4-hydroxymercuribenzoate; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D005979:Glutathione Peroxidase