Biologically relevant mechanism for catalytic superoxide removal by simple manganese compounds
Biologically relevant mechanism for catalytic superoxide removal by simple manganese compounds
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DOI：
10.1073/pnas.1203051109
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发表时间：
2012-05-01
影响因子：
11.1
通讯作者：
Cabelli, Diane E.
中科院分区：
文献类型：
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作者：
Barnese, Kevin;Gralla, Edith Butler;Cabelli, Diane E.
1981年，非酶锰首次被证明可以在体内提供抗超氧化物毒性的保护，但由于有关Mn在体外催化超氧化物分解的能力的报道相互矛盾，这种保护的化学机制随后变得有争议。在最近的一次交流中，我们报道了在生理相关条件下低浓度的简单锰磷酸盐确实会在体外催化超氧化物歧化。我们现在报告，两个四锰复合物，预计是最丰富的体内，锰磷酸盐和锰碳酸盐，可以催化超氧化物歧化在生理相关的浓度和pH值，而锰焦磷酸盐和柠檬酸盐复合物不能。此外，这些反应的化学机理进行了详细的研究，并通过锰磷酸盐和碳酸盐的催化去除超氧化物的反应速率进行了建模。发现这些化合物的生理相关浓度足以模拟体内发现的酶促超氧化物歧化酶的有效浓度。这种机制提供了一个可能的解释，锰如何对抗超氧化物应激细胞系统。
Nonenzymatic manganese was first shown to provide protection against superoxide toxicity in vivo in 1981, but the chemical mechanism responsible for this protection subsequently became controversial due to conflicting reports concerning the ability of Mn to catalyze superoxide disproportionation in vitro. In a recent communication, we reported that low concentrations of a simple Mn phosphate salt under physiologically relevant conditions will indeed catalyze superoxide disproportionation in vitro. We report now that two of the four Mn complexes that are expected to be most abundant in vivo, Mn phosphate and Mn carbonate, can catalyze superoxide disproportionation at physiologically relevant concentrations and pH, whereas Mn pyrophosphate and citrate complexes cannot. Additionally, the chemical mechanisms of these reactions have been studied in detail, and the rates of reactions of the catalytic removal of superoxide by Mn phosphate and carbonate have been modeled. Physiologically relevant concentrations of these compounds were found to be sufficient to mimic an effective concentration of enzymatic superoxide dismutase found in vivo. This mechanism provides a likely explanation as to how Mn combats superoxide stress in cellular systems.