IMPORTANCE OF FE-2+-ADP AND THE RELATIVE UNIMPORTANCE OF OH IN THE MECHANISM OF MITOMYCIN-C-INDUCED LIPID-PEROXIDATION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 796  (3) , 285-293
Abstract
The mechanism of mitomycin C-induced lipid peroxidation was studied at pH 7.5, using systems containing phospholipid membranes (liposomes) and an Fe3+-ADP complex with purified NADPH-cytochrome P-450 reductase. Both O2- and H2O2 are generated during the aerobic enzyme-catalyzed reaction in the presence of mitomycin C. Hydroxyl radical is formed in the reaction by the reduction of H2O2. This is catalyzed by the Fe2+-ADP complex in a phosphate buffer or to a lesser extent when in a Tris-HCl buffer. The reduction of Fe3+-ADP to Fe2+-ADP is mainly achieved by O2-. The resulting Fe2+-ADP in the presence of O2 forms a perferryl Fe complex which is a powerful stimulator of lipid peroxidation. The formation of such an Fe-O2 complex is strongly inhibited by phosphate ions, which do not interfere with the generation of OH radicals. Since lipid peroxidation occurs in a Tris-HCl buffer (but not in a phosphate buffer), the OH radical is unlikely to be involved in the observed lipid peroxidation process.