Dihydrolipoamide-Mediated Redox Cycling of Quinones

The nonenzymatic reactions of dihydrolipoamide with a number of low-potential quinones, possessing either a fully or a partially substituted quinone ring at pH 7.0 were accompanied by consumption of oxygen in a significant excess of the quinone concentration, thus establishing their redox cycling. Contrary to this, only partially substituted quinones caused the consumption of oxygen in the presence of reduced glutathione due to reoxidation of reduced quinone-glutathione conjugates. Among compounds tested, 9,10-phenanthrene quinone catalyzed the most rapid consumption of oxygen in the presence of dihydrolipoamide with subsequent formation of lipoamide and H2O2. The rate constant of anaerobic reduction of phenanthrene quinone by dihydrolipoamide was 8.6 ± 1.6 × 103 M−1 s−1 (pH 7.0, 0.1 M phosphate, 20% ethanol, 25°C). The consumption of oxygen and formation of lipoamide were inhibited by superoxide dismutase, indicating that the redox cycling involves the autooxidation of 9,10-dihydroxy phenanthrene, mediated by superoxide. The reaction was accompanied by the reduction of added cytochrome c, which was insignificantly inhibited by superoxide dismutase, and the reductive mobilization of iron from ferritin, activated by superoxide disniutase. These data raise the possibility that dihydrolipoamide, usually regarded as an antioxidant, under certain conditions may exert moderate prooxidant activity, initiating the formation of radicals and activated forms of oxygen.