Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119899, Russia.
Department of Life Technologies, University of Turku, FIN-20014 Turku, Finland.
Int J Mol Sci. 2022 Aug 22;23(16):9504. doi: 10.3390/ijms23169504.
Membrane pyrophosphatases (mPPases) found in plant vacuoles and some prokaryotes and protists are ancient cation pumps that couple pyrophosphate hydrolysis with the H and/or Na transport out of the cytoplasm. Because this function is reversible, mPPases play a role in maintaining the level of cytoplasmic pyrophosphate, a known regulator of numerous metabolic reactions. mPPases arouse interest because they are among the simplest membrane transporters and have no homologs among known ion pumps. Detailed phylogenetic studies have revealed various subtypes of mPPases and suggested their roles in the evolution of the "sodium" and "proton" bioenergetics. This treatise focuses on the mechanistic aspects of the transport reaction, namely, the coupling step, the role of the chemically produced proton, subunit cooperation, and the relationship between the proton and sodium ion transport. The available data identify H-PPases as the first non-oxidoreductase pump with a "direct-coupling" mechanism, i.e., the transported proton is produced in the coupled chemical reaction. They also support a "billiard" hypothesis, which unifies the H and Na transport mechanisms in mPPase and, probably, other transporters.
植物液泡和一些原核生物及原生生物中的膜焦磷酸酶（mPPases）是古老的阳离子泵，可将焦磷酸水解与细胞质外的 H 和/或 Na 转运偶联。由于该功能是可逆的，mPPases 在维持细胞质中焦磷酸盐水平方面发挥作用，焦磷酸盐是许多代谢反应的已知调节剂。mPPases 引起了人们的兴趣，因为它们是最简单的膜转运蛋白之一，在已知的离子泵中没有同源物。详细的系统发育研究揭示了各种亚型的 mPPases，并提出了它们在“钠”和“质子”生物能量学进化中的作用。本文重点介绍转运反应的机制方面，即偶联步骤、化学产生质子的作用、亚基合作以及质子和钠离子转运之间的关系。现有数据将 H-PPases 确定为具有“直接偶联”机制的首个非氧化还原酶泵，即转运的质子是在偶联化学反应中产生的。它们还支持“弹球”假说，该假说统一了 mPPase 以及可能的其他转运蛋白中的 H 和 Na 转运机制。
