Mechanistic studies on the biosynthesis of 6-ketoprostaglandin F1alpha

Abstract

The isolation, structure and biosynthesis of a novel metabolite of arachidonic acid formed during incubations of rat stomach homogenates is reported. This product was formed from unlabeled, tritium-labeled and deuterium-labeled arachidonic acid and the prostaglandin endoperoxides, G2 and H2, demonstrating its formation via the "prostaglandin endoperoxide synthetase" pathway. Its structure, 6-ketoprostaglandin F1alpha, was based on mass spectral interpretation of several derivatives (undeuterated and deuterated) and confirmed through chemical synthesis. 6-Ketoprostaglandin F1alpha is unique in being formed from a substrate of the "2" series of prostaglandins, i.e. arachidonic acid, yet belonging to the "1" series. A mechanism for its biosynthesis is proposed involving a specific cyclising enzyme which we term, 6(9)-oxycyclase.