Kehres David G, Maguire Michael E
Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4965, USA.
FEMS Microbiol Rev. 2003 Jun;27(2-3):263-90. doi: 10.1016/S0168-6445(03)00052-4.
Though an essential trace element, manganese is generally accorded little importance in biology other than as a cofactor for some free radical detoxifying enzymes and in the photosynthetic photosystem II. Only a handful of other Mn2+-dependent enzymes are known. Recent data, primarily in bacteria, suggest that Mn2+-dependent processes may have significantly greater physiological importance. Two major classes of prokaryotic Mn2+ uptake systems have now been described, one homologous to eukaryotic Nramp transporters and one a member of the ABC-type ATPase superfamily. Each is highly selective for Mn2+ over Fe2+ or other transition metal divalent cations, and each can accumulate millimolar amounts of intracellular Mn2+ even when environmental Mn2+ is scarce. In Salmonella enterica serovar Typhimurium, simultaneous mutation of both types of transporter results in avirulence, implying that one or more Mn2+-dependent enzymes is essential for pathogenesis. This review summarizes current literature on Mn2+ transport, primarily in the Bacteria but with relevant comparisons to the Archaea and Eukaryota. Mn2+-dependent enzymes are then discussed along with some speculations as to their role(s) in cellular physiology, again primarily in Bacteria. It is of particular interest that most of the enzymes which interconvert phosphoglycerate, pyruvate, and oxaloacetate intermediates are either strictly Mn2+-dependent or highly stimulated by Mn2+. This suggests that Mn2+ may play an important role in central carbon metabolism. Further studies will be required, however, to determine whether these or other actions of Mn2+ within the cell are the relevant factors in pathogenesis.
尽管锰是一种必需的微量元素，但在生物学中，除了作为某些自由基解毒酶和光合系统II中的辅因子外，它通常被认为重要性不高。已知的依赖锰离子的酶只有少数几种。最近的数据，主要来自细菌，表明依赖锰离子的过程可能具有显著更高的生理重要性。现在已经描述了两类主要的原核生物锰离子摄取系统，一类与真核生物的天然抗性相关巨噬细胞蛋白（Nramp）转运蛋白同源，另一类是ABC型ATP酶超家族的成员。每一类对锰离子的选择性都远高于亚铁离子或其他过渡金属二价阳离子，并且即使在环境中锰离子稀缺时，每一类都能积累毫摩尔量的细胞内锰离子。在鼠伤寒沙门氏菌中，这两类转运蛋白的同时突变会导致无毒力，这意味着一种或多种依赖锰离子的酶对发病机制至关重要。这篇综述总结了目前关于锰离子转运的文献，主要是关于细菌的，但也与古菌和真核生物进行了相关比较。然后讨论了依赖锰离子的酶，并对它们在细胞生理学中的作用进行了一些推测，同样主要是关于细菌的。特别有趣的是，大多数催化磷酸甘油酸、丙酮酸和草酰乙酸中间体相互转化的酶要么严格依赖锰离子，要么受到锰离子的高度刺激。这表明锰离子可能在中心碳代谢中发挥重要作用。然而，还需要进一步的研究来确定细胞内锰离子的这些或其他作用是否是发病机制中的相关因素。
