Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):6892-7. doi: 10.1073/pnas.1203051109. Epub 2012 Apr 13.
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.
非酶锰于 1981 年首次被证明在体内具有抵抗超氧毒性的作用，但由于有关 Mn 在体外催化超氧歧化的能力的相互矛盾的报告，随后这一保护作用的化学机制引起了争议。在最近的一次交流中，我们报告说，在生理相关条件下，低浓度的简单 Mn 磷酸盐盐确实会在体外催化超氧歧化。我们现在报告说，在体内最丰富的四种 Mn 配合物中，有两种 Mn 磷酸盐和 Mn 碳酸盐，能够在生理相关的浓度和 pH 值下催化超氧歧化，而 Mn 焦磷酸盐和柠檬酸盐配合物则不能。此外，还详细研究了这些反应的化学机制，并对 Mn 磷酸盐和碳酸盐催化去除超氧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存在的酶超氧化物歧化酶的有效浓度。这一机制为 Mn 如何在细胞系统中对抗超氧应激提供了一个可能的解释。
