| Abstract: | Six glutathione-containing inhibitors of the human NADP-linked 15-hydroxyprostaglandin dehydrogenase have been isolated from placental homogenates. Glutathione disulfide is one of these inhibitors. Although the structures of the other five have not been fully elucidated, all are disulfides. Studies with these compounds and with other mixed disulfides have shown that the glutathione mixed disulfides of beta-mercaptopyruvate, mercaptoacetate, and beta-mercaptolactate are more effective inhibitors of the enzyme than are the glutathione-containing mixed disulfides isolated from placental homogenates. beta-Mercaptolactate is particularly noteworthy because of its low Ki (0.13 microM). The results reported here suggest that the activity of the prostaglandin dehydrogenase may be influenced in vivo by various glutathione mixed disulfides. |
