Effect of ascorbate on the DT-diaphorase-mediated redox cycling of 2-methyl-1,4-naphthoquinone.
Following the two-electron reduction of 2-methyl-1,4-naphthoquinone by rat liver DT-diaphorase (also called NAD(P)H: (quinone acceptor) oxidoreductase, EC 1.6.99.2), the hydroquinone product is slowly autoxidized to the quinone in buffered solutions at pH 7.0. The autoxidation, which generates the superoxide radical (O2-.) and other reactive oxygen species, is the rate-limiting step in the oxidation-reduction (redox) cycling of the quinone. The addition of ascorbate to these reaction mixtures increases the rate of redox cycling. Two mechanisms are proposed to explain this increase: (1) ascorbate reduces the quinone in a one-electron reduction and (2) if Fe(3+)-EDTA is present, ascorbate reduces the metal chelate in a one-electron reduction. Both mechanisms produce O2-. which initiates the free radical chain reaction that results in autoxidation of the hydroquinone. Although ascorbate may be a physiologically important antioxidant under some conditions, the studies reported here show that ascorbate is a prooxidant in the redox cycling of 2-methyl-1,4-naphthoquinone and, as such, could increase the potential toxicity of this quinone.
Jarabak
R
R
Department of Medicine, University of Chicago, Illinois 60637, USA.
Jarabak
J
J
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008962:Models, Theoretical; D009249:NADP; D009285:Naphthoquinones / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D024483:Vitamin K 3
D005296:Ferrous Compounds; D009285:Naphthoquinones; C055526:Fe(II)-EDTA; D009249:NADP; D024483:Vitamin K 3; D004492:Edetic Acid; D013482:Superoxide Dismutase; D008058:Dihydrolipoamide Dehydrogenase; D001205:Ascorbic Acid