title: Metabolism of 5(6)Oxidoeicosatrienoic acid by ram seminal vesicles. Formation of two stereoisomers of 5-hydroxyprostaglandin I1.
abstract: Cytochrome P-450 can metabolize arachidonic (5,8,11,14-eicosatetraenoic) acid to four epoxides. One of them, cis-5(6)oxido-8,11,14-eicosatrienoic acid, has been reported to possess biological activity. To ascertain whether this epoxide could be a substrate for the enzyme fatty acid cyclooxygenase, synthetic 3H-labeled cis-5(6)-oxido-8,11,14-eicosatrienoic acid was incubated with microsomes of ram seminal vesicles and incubated with microsomes of ram seminal vesicles and the products were separated by reversed phase high performance liquid chromatography. The substrate was enzymatically transformed into products, which were more polar than 5,6-dihydroxy-8,11,14-eicosatrienoic acid. The biosynthesis was strongly inhibited by indomethacin or diclofenac sodium, two inhibitors of fatty acid cyclooxygenase. Two of the major metabolites could be identified by capillary gas chromatography-mass spectrometry as two stereoisomers of 5-hydroxyprostaglandin I1, viz. (5R,6R)-5-hydroxyprostaglandin I1 and (5S,6S)-5-hydroxyprostaglandin I1. The structures were established by comparison with the mass spectra of authentic material and by the retention time on capillary gas chromatography using deuterated internal standards. The two stereoisomers were presumably formed nonenzymatically from the intermediate 5(6)oxidoprostaglandin endoperoxides or from 5(6)oxidoprostaglandin F1 alpha during the isolation procedure.
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D011464:Epoprostenol / Q000378:metabolism* / Q000031:analogs & derivatives; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D012669:Seminal Vesicles / Q000378:metabolism*; D012756:Sheep; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C040763:5-hydroxyprostaglandin I; D005231:Fatty Acids, Unsaturated; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D011464:Epoprostenol; D015126:8,11,14-Eicosatrienoic Acid