Copper + zinc and manganese superoxide dismutases inhibit deoxyribose degradation by the superoxide-driven Fenton reaction at two different stages. Implications for the redox states of copper and manganese.
When OH. radicals are formed in a superoxide-driven Fenton reaction, in which O2.- is generated enzymically, deoxyribose degradation is effectively inhibited by CuZn- and Mn-superoxide dismutases. The products of this reaction are H2O2 and a Fe3+-EDTA chelate. The mixing of H2O2 and a Fe3+-EDTA chelate also generates OH. radicals able to degrade deoxyribose with the release of thiobarbituric acid-reactive material. This reaction too is inhibited by CuZn- and Mn-superoxide dismutases, suggesting that most of the OH. is formed by a non-enzymic O2.--dependent reduction of the Fe3+-EDTA chelate. Since the reaction between the Fe3+-EDTA chelate and H2O2 leads to a superoxide dismutase-inhibitable formation of OH. radicals, it could suggest a much wider protective role for the superoxide dismutase enzymes in biological systems. Urate produced during the reaction of xanthine oxidase and hypoxanthine limits deoxyribose degradation as well as the effectiveness of the superoxide dismutase enzymes to inhibit damage to deoxyribose by H2O2 and the Fe3+-EDTA chelate. Some of this damage may result from an O2.--independent pathway to OH. formation in which urate reduces the ferric complex.
D002413:Cations, Divalent / Q000494:pharmacology; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D003855:Deoxyribose / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D014527:Uric Acid / Q000494:pharmacology
D002413:Cations, Divalent; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D013481:Superoxides; D014527:Uric Acid; D008345:Manganese; D003855:Deoxyribose; D003300:Copper; D004492:Edetic Acid; D013482:Superoxide Dismutase; C019179:Fe(III)-EDTA