Polycyclic aromatic hydrocarbon quinones and glutathione thioethers as substrates and inhibitors of the human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase.

The human placental NADP-linked 15-hydroxyprostaglandin dehydrogenase catalyzes oxidoreduction at the 9- and 15-positions of many prostaglandins, but its catalytic efficiency (i.e. kcat/Km) for these reactions is low (Jarabak, J., Luncsford, A., and Berkowitz, D. (1983) Prostaglandins 26, 849-868). In the present study, we demonstrate that both K-region and non-K-region o-quinones of polycyclic aromatic hydrocarbons are excellent substrates for this enzyme. These compounds are reduced with kcat/Km values ranging from 3 to 20 X 10(6) S-1 M-1. The glutathione thioethers of menadione and toluquinone are reduced with similar catalytic efficiencies. Furthermore, these substances and certain other glutathione thioethers are potent inhibitors of prostaglandin B1 oxidation ([I50] = 7 X 10(-8) to 5 X 10(-6) M); while several glutathione thioethers also inhibit polycyclic aromatic hydrocarbon quinone reduction ([I50] = 1.7-6.5 microM). These findings raise the possibility that the potential toxicity of quinones of polycyclic aromatic hyrocarbons and other xenobiotic substances may be altered in the placenta by an oxidoreductase for which prostaglandins are relatively poor substrates. They also suggest that the presence in placental tissue of certain glutathione thioethers could influence the reduction of these quinones and other xenobiotic substances by this enzyme.