Polycyclic aromatic hydrocarbon quinones may be either substrates for or irreversible inhibitors of the human placental NAD-linked 15-hydroxyprostaglandin dehydrogenase.
Under aerobic conditions, 9,10-phenanthrenequinone and 5,6-chyrsenequinone undergo oxidation-reduction cycling in the presence of NADH and the NAD-linked 15-hydroxyprostaglandin dehydrogenase. This results in the formation of potentially hazardous semiquinones, the superoxide anion, and H2O2. Superoxide dismutase inhibits this cycling by destroying the free radical chain propagator, the superoxide anion. Four other polycyclic aromatic hydrocarbon quinones are not substrates of the enzyme and they cause it to undergo a time-dependent inactivation. This presumably results from alkylation of the enzyme. Glutathione fully protects the enzyme against inactivation by 1,2-naphthoquinone but is only partially effective against 7,8-benzo[a]pyrenequinone. These results suggest that in tissues which contain the NAD-linked 15-hydroxyprostaglandin dehydrogenase some polycyclic aromatic hydrocarbon quinones might produce deleterious effects by undergoing redox cycling. Others might cause such effects by irreversibly inhibiting the enzyme which catalyzes the first step in prostaglandin catabolism.
Jarabak
J
J
Department of Medicine, University of Chicago, Illinois 60637.
D000527:Alprostadil / Q000037:antagonists & inhibitors; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D010084:Oxidation-Reduction / Q000187:drug effects; D010920:Placenta / Q000201:enzymology*; D011083:Polycyclic Compounds / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000737:chemistry
D011083:Polycyclic Compounds; D011809:Quinones; D013481:Superoxides; D006861:Hydrogen Peroxide; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D013482:Superoxide Dismutase; D000527:Alprostadil