A novel cyclooxygenase metabolite of arachidonic acid.

Abstract The 8000 X g pellet of rabbit placenta transformed arachidonic acid into a number of lipoxygenase and cyclooxygenase products of known structure. A metabolite was also produced which was inhibited by indomethacin and required calcium for its formation. This compound had a UV absorption maximum at 227 nm under acidic or neutral conditions and gave a bathochromic shift to 281 nm under alkaline conditions. Reduction of this metabolite with sodium borohydride produced prostaglandin (PG) F2 alpha (as determined by mass spectrometry), while catalytic hydrogenation increased the molecular weight by four mass units, indicating the presence of two double bonds. Based on the mass spectrum of the derivatized metabolite, the structure proved to be 9,15-dioxo-11-hydroxyprosta-5,13-dienoic acid. This compound is produced by the term placenta and does not appear to be formed from PGE2, PGF2 alpha, or PGD2. The compound is suppressed by GSH and NADPH, but its formation is not increased by NAD or NADP. PGH2 and PGG2 are not converted to 9,15-dioxo-11-hydroxyprosta-5,13-dienoic acid under similar in vitro incubation conditions. This therefore represents conversion of arachidonate to 9,15-dioxo-11-hydroxyprosta-5,13-dienoic acid through a Ca2+-dependent, non-PG dehydrogenase pathway.