Identification of 15-keto-9, 11-peroxidoprosta-5, 13- dienoic acid as a hematin-catalyzed decomposition product of 15-hydroperoxy-9, 11-peroxidoprosta-5, 13-dienoic acid

Abstract

A labile prostaglandin was isolated as one of the products generated from [1-14C] eicosatetraenoic acid incubated with sheep vesicular gland microsomes. The eicosatetraenoic acid metabolite amounted to ca. 16% of the total radiolabeled products. Formation of this new prostaglandin was prevented when heat-denatured microsomes were employed or when incubation mixtures were supplemented with indomethacin or phenol. However, incubation of prostaglandin G2 (PGG2) with hematin in the presence or absence of catalytically active or heat-inactivated microsomes led to production of approximately the same quantity of the new prostaglandin. These results indicated that the new prostaglandin can be formed nonenzymically. The new prostaglandin was conclusively identified by gas liquid chromatography-mass spectrometry analysis as 15-keto-9,11-peroxidoprosta-5,13-dienoic acid (15-keto-PGG2) after chemical conversion to known prostaglandins. The effects of 15-keto-PGG2 and PGG2 were similar on canine lateral saphenous vein; both promoted contraction followed by prolonged relaxation, but 15-keto-PGG2 appeared to be 1/50 as potent as PGG2.