Polycyclic aromatic hydrocarbon quinone-mediated oxidation reduction cycling catalysed by a human placental 17beta-hydroxysteroid dehydrogenase.
The human placental 17beta-hydroxysteroid dehydrogenase reduces a number of polycyclic aromatic hydrocarbon (PAH) o-quinones; some of the quinones undergo redox cycling at rates that approach or exceed the rate of reduction of estrone by the enzyme. The non-K-region o-quinone, 7,8-benzo[a]pyrenequinone, is the best o-quinone substrate tested. Cycling of all the quinone substrates is inhibited by superoxide dismutase; cycling is also inhibited by 17beta-estradiol and other estrogens. Since 19 alpha-estradiol is a competitive inhibitor of 9,10-phenanthrenequinone by the 17beta-hydroxysteroid dehydrogenase, it is likely that both reactions occur at the same active site on the enzyme. In the presence of the 17beta-hydroxysteroid dehydrogenase, the equilibrium between 17beta-estradiol, estrone, NADP, and NADPH is shifted by 7,8-benzo[a]pyrenequinone because the rapid redox cycling of this quinone results in the oxidation of NADPH. Unlike a number of hydroxysteroid dehydrogenases, the placental 17beta-hydroxysteroid dehydrogenase does not oxidize any of the six PAH trans-dihydrodiols tested.
Jarabak
R
R
Department of Medicine, University of Chicago, Illinois 60637, USA.
Harvey
R G
RG
Jarabak
J
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology*; D011083:Polycyclic Compounds / Q000378:metabolism*; D011247:Pregnancy; D011809:Quinones / Q000378:metabolism*; D013379:Substrate Specificity
D000728:Androgens; D004791:Enzyme Inhibitors; D004967:Estrogens; D011083:Polycyclic Compounds; D011809:Quinones; D015067:17-Hydroxysteroid Dehydrogenases