ABSTRACT
The successive monoelectronic steps of biological oxygen reduction, generally catalyzed by transition metal ions such as copper and iron, produce potentially harmful reactive oxygen-derived species-superoxide, hydrogen peroxide, and hydroxyl radical-and the innocuous water molecule. Lipid peroxidation may already be associated with the initiating process, producing superoxide, which is in turn able to liberate some reduced metals, e.g., Fe2+, from their metalloproteins and also to deesterify fatty acids from their esters. Therefore, peroxides, particularly lipid hydroperoxides, may be generated and may propagate radical generation after their own metal-
catalyzed decomposition, in which metal chelators may share a prominent modulatory role. A competition may take place between these respective processes of stepwise oxygen reduction and the overall mitochondrial respiration, which supplies energy for cellular requirements. Damage to the electron chain of mitochondria, e.g., after ischemia in the brain, probably results from rapid peroxidative reactions following release of free fatty acids (1). Although some underlying mechanisms involving oxygen-derived radicals were not yet understood, the relationship between peroxide toxicity (e.g., that of autoxidized squalene and linoleic acid) and irradiation lethality were hypothesized as early as 1958 (2).
