On the Mechanism of the Biosynthesis of Prostaglandins E1 and F1α

Abstract

The mechanism of the conversion of 8,11,14-eicosatrienoic acid into prostaglandin E1 (PGEl) and prostaglandin F1, (PGFI,) has been studied.Incubation of [13~-~H,3-"C]and [13~-3H ,3J*C]8,11,14-eicosatrienoic acids showed that the hydrogen removed from C-13 during the conversion into PGEl and PGFI, has the L configuration.The conversion of [13~-3H ,3J4C]8, 11,14-eicosatrienoic acid into PGEl is accompanied by a hydrogen isotope effect.No conversion of [ 2 J*C]lSL-hydroperoxy -8(cis), ll(cis) ,13(trans) -eicosatrienoic acid or [2-'*C]lSL-hydroxy-8(cis), ll(cis) , lJ(frans)eicosatrienoic acid into PGEl or PGFI, could be detected.Incubations of [9-3H ,3J4C]8,11 ,14-eicosatrienoic acid revealed that PGF1, is not formed via PGEl in the system used.The mechanistic implications of the results obtained are discussed.It is suggested that 11-peroxy-8,12,14-eicosatrienoic acid is the first intermediate in the conversion.The peroxy acid is cyclized into an endoperoxide, which is eventually transformed into PGEl or PGF,, by independent reactions.