Identification of an unusual cyclooxygenase metabolite of arachidonic acid in rabbit renal medulla.
A renal medulla 100,000g pellet metabolized arachidonic acid, C20:4, to the previously described prostaglandins prostaglandin E2, 6-ketoprostaglandin F1 alpha, thromboxane B2, 12-hydroxyheptadecatrienoic acid, and 11-hydroxyeicosatetraenoic acid. In addition, under conditions of low enzyme to substrate ratios, the renal medulla also produced an unusual metabolite from arachidonic acid. This metabolite was inhibited by indomethacin, and thus suggested that it was a product of the cyclooxygenase. Addition of GSH to the incubation inhibited its formation, while p-hydroxymercuribenzoate enhanced its formation. This compound was identified by HPLC purification, uv absorption, and gas chromatography-mass spectroscopy. The compound was 9,15-dioxo,11-hydroxyprosta-5,13-dienoic acid.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D005978:Glutathione / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; C026346:15-ketoprostaglandin E2; D013929:Thromboxane B2; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; C025559:12-hydroxy-4,8,10-heptadecatrienoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D005978:Glutathione; D015232:Dinoprostone; D007213:Indomethacin