THE OXIDATION OF CYTOCHROME-C-OXIDASE VESICLES BY HEMOGLOBIN

Human hemoglobin has been used as a pro-oxidant for artificial unilame llar phospholipid vesicles, containing cytochrome-c oxidase inserted i nto the bilayer. This experimental system was suitable to follow direc tly the kinetics of lipid oxidation and the effects on both the vesicl e membrane permeability and the functional state of cytochrome-c oxida se. Following mixing of vesicles with hemoglobin, an oxygen dependent, peroxyl radical mediated, rapid oxidation (taking a few minutes) of t he lipid was found to occur. On a similar time scale the membrane beca me ion-leaky and cytochrome-c oxidase damaged. The pro-oxidant effects of hemoglobin in various oxidation and ligation states were studied a nd a mechanism, based on a ferric/ferryl redox cycle of the heme-iron is proposed to account for these observations.