Superoxide reaction with nucleic acids

Several powerful oxidants are produced during the course of metabolism, in both blood cells and most other cells of the body. These include superoxide (02 ), hydrogen peroxide (H2O2), peroxyl radicals (ROO ), and hydroxyl radicals (OH ). The last is a particularly reactive molecule and can react with proteins, nucleic acids, lipids, and other molecules to alter their structure and produce tissue damage. The reactions listed in Table 52-4 play an important role in forming these oxidants and in disposing of them each of these reactions will now be considered in turn. 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

Vittimin E functions as a lipid antioxidemt both in vitro emd in vivo a number of synthetic tmtioxidants will prevent or cure most of the signs of vitamin E deficiency in experimenttil animeds. Polyunsaturated fatty acids undergo oxidative attack by hydroxyl radicals and superoxide to yield tdkylperoxyl (cdkyl-dioxyl) radicals, which perpetuate a chtun reaction in the Upid - with potentiedly disastrous consequences for cells. Similar oxidative radictd damage cem occur to proteins (especially in a lipid environment) and nucleic acids. 

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