Murakami Keiko, Yoshino Masataka
Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
Biometals. 2015 Aug;28(4):687-91. doi: 10.1007/s10534-015-9856-6. Epub 2015 May 5.
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.
分析了1,6-二磷酸果糖介导的铁氧化在活性氧生成中的作用。乌头酸酶是对氧化应激最敏感的酶，在亚铁离子存在下，1,6-二磷酸果糖能有效使其失活，ADP和PEP在较小程度上进一步增强这种失活作用。这种失活作用需要氰化物，表明超氧阴离子自由基是导致失活的原因。添加抗坏血酸和二硫苏糖醇可防止乌头酸酶失活。1,6-二磷酸果糖、ADP和PEP刺激亚铁离子氧化，导致氧分子单电子还原。铁氧化形成的超氧阴离子自由基参与乌头酸酶的氧化失活和柠檬酸循环，导致克奈特效应的诱导，即高葡萄糖介导的线粒体氧化代谢抑制。
