REDOX CYCLING OF MPP+ - EVIDENCE FOR A NEW MECHANISM INVOLVING HYDRIDE TRANSFER WITH XANTHINE-OXIDASE, ALDEHYDE DEHYDROGENASE, AND LIPOAMIDE DEHYDROGENASE

MPP+ is redox active in the presence of cytochrome P450 reductase and induces the formation of O2.- and HO.. In this study, we report the redox cycling capability of MPP+ with additional enzymes and with UV photolysis detected through ESR techniques. The treatment of MPP+ with UV light resulted in the production of HO' trapped as a spin adduct. Two of the enzymes examined in this study, xanthine oxidase and aldehyde dehydrogenase, produced 02'- in the presence of substrate. However, when MPP+ was added to the incubations, the radical trapped by DMPO was HO'. This indicates that MPP+ redox cycles in the presence of these two enzymes or UV light, which produces HO.. Our data also suggest that MPP+ is reduced by lipoamide dehydrogenase. MPP+ stimulated the oxidation of reduced nicotinamide adenine dinucleotide (NADH) by the enzyme at concentrations between 2 mM and 8 mM of MPP+. Higher concentrations of MPP+ inhibited lipoamide dehydrogenase. MPP+ appears to be redox active with a number of redox enzymes. The mechanism involved may be hydride transfer from the enzymes to MPP+, rather than a direct single-electron reduction.