Research Service, North Florida/South Georgia Veterans Health System, Gainesville, Florida, USA.
Am J Physiol Renal Physiol. 2010 Jan;298(1):F12-21. doi: 10.1152/ajprenal.90723.2008. Epub 2009 Jul 29.
The H(+)-K(+)-ATPases are ion pumps that use the energy of ATP hydrolysis to transport protons (H(+)) in exchange for potassium ions (K(+)). These enzymes consist of a catalytic alpha-subunit and a regulatory beta-subunit. There are two catalytic subunits present in the kidney, the gastric or HKalpha(1) isoform and the colonic or HKalpha(2) isoform. In this review we discuss new information on the physiological function, regulation, and structure of the renal H(+)-K(+)-ATPases. Evaluation of enzymatic functions along the nephron and collecting duct and studies in HKalpha(1) and HKalpha(2) knockout mice suggest that the H(+)-K(+)-ATPases may function to transport ions other than protons and potassium. These reports and recent studies in mice lacking both HKalpha(1) and HKalpha(2) suggest important roles for the renal H(+)-K(+)-ATPases in acid/base balance as well as potassium and sodium homeostasis. Molecular modeling studies based on the crystal structure of a related enzyme have made it possible to evaluate the structures of HKalpha(1) and HKalpha(2) and provide a means to study the specific cation transport properties of H(+)-K(+)-ATPases. Studies to characterize the cation specificity of these enzymes under different physiological conditions are necessary to fully understand the role of the H(+)-K(+) ATPases in renal physiology.
H(+)-K(+)-ATPases 是离子泵，利用 ATP 水解的能量将质子 (H(+)) 逆浓度梯度转运，同时将钾离子 (K(+)) 顺浓度梯度转运。这些酶由一个催化亚基和一个调节亚基组成。肾脏中存在两种催化亚基，胃或 HKalpha(1)同工型和结肠或 HKalpha(2)同工型。在这篇综述中，我们讨论了关于肾脏 H(+)-K(+)-ATPases 的生理功能、调节和结构的新信息。对沿肾单位和集合管的酶功能的评估以及在 HKalpha(1)和 HKalpha(2)基因敲除小鼠中的研究表明，H(+)-K(+)-ATPases 可能具有转运质子和钾以外的离子的功能。这些报告和最近在缺乏 HKalpha(1)和 HKalpha(2)的小鼠中的研究表明，肾脏 H(+)-K(+)-ATPases 在酸碱平衡以及钾和钠稳态中具有重要作用。基于相关酶的晶体结构的分子建模研究使得评估 HKalpha(1)和 HKalpha(2)的结构成为可能，并为研究 H(+)-K(+)-ATPases 的特定阳离子转运特性提供了一种手段。在不同生理条件下表征这些酶的阳离子特异性的研究对于充分了解 H(+)-K(+)ATPases 在肾脏生理学中的作用是必要的。
