Concerted action of reduced glutathione and superoxide dismutase in preventing redox cycling of dihydroxypyrimidines, and their role in antioxidant defence.
Dialuric Acid, the reduced form of the beta-cell toxin alloxan, and the related fava bean derivatives divicine and isouramil, autoxidize rapidly in neutral solution by a radical mechanism. GSH promotes redox cycling of each compound, with concomitant GSH oxidation and H2O2 production. With superoxide dismutase present, there is a lag period in which little oxidation occurs, followed by rapid oxidation. GSH extends this lag and decreases the subsequent rate of oxidation, so that with superoxide dismutase and a sufficient excess of GSH, coupled oxidation of GSH and each pyrimidine is almost completely suppressed. This mechanism may be a means whereby GSH in combination with superoxide dismutase protects against the cytotoxic effects of these reactive pyrimidines. Superoxide dismutase may also protect cells against oxidative stress in other situations where GSH acts as a radical scavenger, and we propose that the concerted action of GSH and superoxide dismutase constitutes an important antioxidant defence.
Winterbourn
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CC
Department of Pathology, School of Medicine, Christchurch Hospital, New Zealand.
Munday
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R
D000975:Antioxidants / Q000032:analysis*; D001463:Barbiturates / Q000032:analysis*; D055598:Chemical Phenomena; D002621:Chemistry; D005978:Glutathione / Q000032:analysis*; D010084:Oxidation-Reduction; D011744:Pyrimidinones / Q000032:analysis*; D013482:Superoxide Dismutase / Q000032:analysis*
D000975:Antioxidants; D001463:Barbiturates; D011744:Pyrimidinones; C026511:divicine; C032211:isouramil; C004718:dialuric acid; D013482:Superoxide Dismutase; D005978:Glutathione