Chaudhari A, Anderson M W, Eling T E
Biochim Biophys Acta. 1978 Oct 25;531(1):56-64. doi: 10.1016/0005-2760(78)90181-9.
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.
15-酮基[³H]前列腺素F2α与谷胱甘肽(GSH)一起温育,产生了一种15-酮基前列腺素F2α的代谢产物,该产物不能从水溶液中萃取出来,因此被称为“水溶性代谢产物”。向温育混合物中加入豚鼠肝脏的胞质溶胶,可使15-酮基前列腺素F2α的水溶性代谢产物的生成增加3倍。在有无酶存在的情况下,15-酮基前列腺素F2α向水溶性代谢产物的转化在温育10分钟期间呈线性,且最大活性需要2.5 mM GSH。肝脏和肾脏胞质溶胶的活性分别约为肺胞质溶胶的70倍和25倍。对由15-酮基[³H]前列腺素F2α与GSH温育或[³H]GSH与15-酮基前列腺素F2α温育所得到的水溶性代谢产物进行色谱分析表明,该水溶性代谢产物是15-酮基前列腺素F2α与GSH的加合物。向温育混合物中加入GSH S-转移酶的底物前列腺素A1,可竞争性抑制15-酮基[³H]前列腺素F2α的水溶性代谢产物的形成。据推测,15-酮基前列腺素F2α和其他15-酮基前列腺素可被GSH S-转移酶转化为GSH缀合物。这表明前列腺素脱氢酶产生的15-酮基代谢产物可能会进一步代谢为GSH缀合物。