Effect of fructose 1,6-bisphosphate on the iron redox state relating to the generation of reactive oxygen species

Role of fructose 1,6-bisphosphate-mediated iron oxidation in the generation of reactive oxygen species was analyzed. Aconitase the most sensitive enzyme to oxidative stress was inactivated potently by fructose 1,6-bisphosphate in the presence of ferrous ion, and further by ADP and PEP to a lesser extent. The inactivation requires cyanide, suggesting that the superoxide radical is responsible for the inactivation. Addition of ascorbic acid and dithiothreitol prevented aconitase from the inactivation. Fructose 1,6-bisphosphate, ADP and PEP stimulated the oxidation of ferrous ion causing one-electron reduction of oxygen molecule. Superoxide radical formed with iron oxidation participates in the oxidative inactivation of aconitase and the citric acid cycle, resulting in the induction of the Crabtree effect, that is, high glucose-mediated inhibition of oxidative metabolism in mitochondria.