Enzymatic transformation of PGH2 to PGF2α catalyzed by glutathione S-transferases

Abstract Glutathione S-transferases (GSTs) purified from both rat liver cytosol and microsomes catalyzed the direct reduction of PGH 2 to PGF 2α . As much as 40% of the substrate was transformed into a prostanoid whose R f value corresponded to that of PGF 2α . The identification of the reaction product as PGF 2α was confirmed by TLC and reverse-phase HPLC as well as by mass spectral analysis. In the absence of GSTs, PGH 2 was found to be primarily converted to PGE 2 and PGD 2 . Also, PGF 2α formation was completely abolished by decylglutathione, a potent inhibitor of both peroxidase and transferase activity associated with GSTs. These results indicate that the direct reduction of endoperoxide moiety of PGH 2 to form PGF 2α is an enzymatic process. Interestingly, selenium-dependent glutathione peroxidase (Se-GSH-Px) showed very little PGF 2α formation from PGH 2 . However, this enzyme was very active in the reduction of PGG 2 to PGH 2 . In contrast, GSTs were very poor in the conversion of PGG 2 to PGH 2 . Therefore, it is possible that the relative tissue distribution of Se-GSH-Px and GSTs might play an important role in the tissue specific synthesis of PGF 2α .