REDOX CYCLING OF BETA-LAPACHONE AND RELATED O-NAPHTHOQUINONES IN THE PRESENCE OF DIHYDROLIPOAMIDE AND OXYGEN

Lipophilic o-naphthoquinones (beta-lapachone, CG 8-935, CG 9-442, CG 1 0-248, and mansonones A, C, E, and F), catalyze the oxidation of dihyd rolipoamide (DHLA) by oxygen, whereas rho-naphthoquinones (alpha-lapac hone and menadione) are scarcely active. The greatest effects correspo nded to beta-lapachone and its analogues. Quinol production was demons trated by (a) the absorption spectrum of the reduced quinone, and (b) the effect of pH variation on the rate of quinone-catalyzed DHLA oxida tion. Superoxide dismutase (SOD) inhibited the rate of cytochrome c re duction and decreased the apparent rate of oxygen consumption by sever al DHLA/o-naphthoquinone systems. SOD also inhibited the rate of quino l oxidation by oxygen, after quinone reduction by a stoichiometric amo unt of DHLA. Catalase enhanced the effect of SOD, but in its absence c atalase was inactive. It is concluded that quinone-catalyzed oxidation of DHLA implies a free-radical mechanism in which the quinol and supe roxide radicals play an essential role.