Cytochrome P-450 under conditions of oxidative stress: role of antioxidant recycling in the protection mechanisms.

Abstract

Free radicals initiate lipid peroxidation of microsomal membranes by rapidly forming lipid hydroperoxides (LOOH) from endogenous polyunsaturated fatty acid residues of phospholipids. Lipid hydroperoxides may in turn propagate lipid peroxidation via the cytochrome P-450-dependent mechanism. Indeed cytochrome P-450 catalyzes the oxidative cleavage of lipid hydroperoxides to a pool of alkoxyl- (LO) and peroxyl-LOO) radicals which induce an additional formation of lipid hydroperoxides. Propagation and termination of lipid peroxidation in the cell are accompanied by a concomitant accumulation of numerous lipid peroxidation products possessing different effects on biomembranes and membrane bound enzymes (Halliwell and Gutteridge, 1985; Kagan, 1988). However, these products originate from hydroperoxides, the primary molecular lipid peroxidation products, which can be reduced to corresponding hydroxy-compounds by peroxidases (Christophersen, 1969; Ursini et al., 1985) thus preventing the formation of various scission products. Lipid peroxidation is considered to be an efficient triggering mechanism of the disassembly of microsomal membranes and cytochrome P-450.