Conjugation of 15-keto-prostaglandins by glutathione S-transferases.
Incubation of 15-keto[3H]prostaglandin F2alpha with glutathione (GSH) produced a metabolite of 15-keto-prostaglandin F2alpha which was not extractable from aqueous solution and thus termed 'water-soluble metabolite'. The addition of cytosol of guinea pig liver to the incubation mixture increased the formation of water soluble metabolite of 15-keto-prostaglandin F2alpha 3-fold. The conversion of 15-keto-prostaglandin F2alpha to water soluble metabolite in both the presence and absence of enzyme was linear during 10 min of incubation and required 2.5 mM GSH for maximal activity. Liver and kidney cytosol possess about 70 and 25 times, respectively, as much activity as compared to lung cytosol. Chromatographic analysis of the water soluble metabolite obtained from incubation of either 15-keto[3H]prostaglandin F2alpha and GSH or [3H]GSH and 15-keto-prostaglandin F2alpha showed that the water-soluble metabolite was an adduct of 15-keto-prostaglandin F2alpha and GSH. The addition of prostaglandin A1, a substrate of GSH S-transferases, to the incubation mixture competitively inhibited the formation of the water-soluble metabolite of 15-keto[3H]prostaglandin F2alpha. Presumably, 15-keto-prostaglandin F2alpha and other 15-keto-prostaglandins are converted to GSH conjugates by GSH S-transferases. This indicates that 15-keto-metabolites produced by prostaglandin dehydrogenase may be further metabolized to GSH conjugates.
D000818:Animals; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006168:Guinea Pigs; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology; D011454:Prostaglandins A / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism*
D011453:Prostaglandins; D011454:Prostaglandins A; D011460:Prostaglandins F; D005982:Glutathione Transferase