Free radicals and environmental toxins.
Some chemicals that contaminate our environment exert their toxic effects by virtue of their ability to form free radicals. In the absence of sufficient quenching reactions, these reactive radicals can attack biomolecules, resulting in their oxidative degradation. Biological membranes which contain polyunsaturated fatty acids are most susceptible to oxidative degradation (lipid peroxidation), although oxidation of DNA may have more severe biological consequences. Free radicals species can be generated by at least two mechanisms in vivo. The first, of which carbon tetrachloride (CCl4) is the classic example, is the biotransformation of the chemical to a free radical species. Metabolism of CCl4 to the trichloromethyl radical by the hepatic mixed-function oxidase system results in the initiation of lipid peroxidation, protein-lipid cross linkages, and trichloromethyl adducts with DNA, protein, and lipid. The second mechanism for forming free radicals involves their reduction to less stable free radical intermediates which are oxidized by molecular oxygen to give superoxide (O2-.). In the presence of transition metals, such as iron, O2-. can be converted to other oxygen radical species, such as the hydroxyl radical (.OH), an extremely powerful oxidant capable of cleaving DNA, oxidizing protein, and initiating lipid peroxidation. Under many conditions, lipid peroxidation appears not to be initiated by .OH, but rather by an iron-oxygen complex. Regardless of the identity of the initiating species, transition metals are required for most of the deleterious reactions of oxygen. Superoxide and certain organic radicals have been found to release iron from ferritin.
Mixed Function Oxygenases
Pub Type(s)Journal Article