Studies on three reductases which have polycyclic aromatic hydrocarbon quinones as substrates.
Unlike rodent tissues, the major quinone reductase in centrifuged homogenates of human liver and placenta is a carbonyl reductase rather than a DT-diaphorase. When reduction of polycyclic aromatic hydrocarbons is compared, there are differences between the human placental carbonyl reductase, rat liver DT-diaphorase, and Clostridium DT-diaphorase. In a buffer containing 1% albumin and 10 microM quinone, 9,10-phenanthrenequinone is reduced most rapidly by the carbonyl reductase, 2-methyl-1,4-naphthoquinone is reduced most rapidly by the rat enzyme, and 3,6-pyrenequinone is reduced most rapidly by the Clostridium enzyme. In the presence of O2, redox cycling occurs with all of the quinones that are enzyme substrates, but the rate of cycling does not necessarily correlate with that of quinone reduction. Since glutathionyl adducts of certain quinones can undergo redox cycling mediated by the human carbonyl reductase or rat DT-diaphorase, it is unlikely that the conjugation of one of these quinones with glutathione is sufficient to protect against quinone-mediated oxidative stress in cells which contain either of these enzymes. The observation that superoxide dismutase and a dismutase "mimic," 3-carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl, inhibit the redox cycling of 9,10-phenanthrenequinone suggests a mechanism whereby cells could be protected against oxidative stress caused by certain quinones.
Jarabak
J
J
Department of Medicine, University of Chicago, Illinois 60637.
Harvey
R G
RG
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D002498:Centrifugation; D003013:Clostridium / Q000201:enzymology; D001728:Dicumarol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011083:Polycyclic Compounds / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000494:pharmacology
D011083:Polycyclic Compounds; D009243:NAD; D009249:NADP; D012431:Rutin; D001728:Dicumarol; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D016660:NAD(P)H Dehydrogenase (Quinone)