The reduction of alpha-tocopherolquinone by human NAD(P)H: Quinone oxidoreductase: The role of alpha-tocopherolhydroquinone as a cellular antioxidant

alpha-Tocopherolquinone (TQ), a product of alpha-tocopherol oxidation, can function as an antioxidant after reduction to alpha-tocopherolhydroquinone (TQH(2)). We examined the ability of human NAD(P)H:quinone oxidoreductase (NQO1) to catalyze the reduction of TQ to TQH(2) in cell-free and cellular systems. In reactions with purified human NQO1, TQ was reduced to TQH(2). Kinetic parameters for the reduction of TQ by NQO1 (K-m = 370 mu M; k(cat) = 5.6 X 10(3 min-1); k(cat/)K(m) = 15 min(-1) . mu M-1) indicate that NQO1 can efficiently reduce TQ to TQH(2). A comparison of the rate of reduction of TQ and coenzyme Q(10) by NQO1 showed that TQ is reduced more efficiently than coenzyme Q(10). Experiments with either Chinese hamster ovary (CHO) cells stably transfected with human NQO1 or CHO cell sonicates demonstrated a correlation between NQO1 activity and TQ reduction to TQH(2). CHO cells with elevated NQO1 generated and maintained higher levels of TQH(2) after treatment with TQ relative to NQO1-deficient CHO cells, TQH(2) generated from NQO1-mediated reduction of TQ prevented cumene hydroperoxide-induced lipid peroxidation in rat liver microsomes. In addition, cumene hydroperoxide-induced lipid peroxidation was inhibited more efficiently by TQ in CHO cell lines with elevated NQO1 activity. These data demonstrate that NQO1 can reduce TQ to TQH(2) and that TQH(2) can function as an efficient antioxidant. This work suggests that one of the physiological functions of NQO1 may be to regenerate antioxidant forms of alpha-tocopherol.