Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney.

Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney.
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DOI:
10.3390/ijms24044251
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发表时间:
2023-02-20
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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碳酸酐酶(CAs),因为它们催化二氧化碳(CO2)和水相互转化为碳酸氢盐(HCO3−)和质子(H+),从而影响pH值,几乎是体内所有生理过程的核心。在肾脏中,可溶性和膜相关的CAs及其与酸碱转运蛋白的协同作用在尿酸分泌中起重要作用,其中最大的成分是特定肾单元段HCO3−的重吸收。在这些转运体中,Na+偶联HCO3 -转运体(NCBTs)和Cl -HCO3 -交换体(AEs)是“溶质连接载流子”4 (SLC4)家族的成员。所有这些转运体传统上都被认为是“HCO3 -”转运体。然而,最近我们的研究小组已经证明,其中两个NCBTs携带CO32 -而不是HCO3 -,并假设所有NCBTs都是如此。在这篇综述中,我们研究了目前关于CAs和SLC4家族“HCO3 -”转运体在肾酸碱生理中的作用的知识,并讨论了我们最近的发现如何影响肾酸分泌,包括HCO3 -重吸收。传统上,研究人员将CAs与产生或消耗溶质(CO2, HCO3−和H+)联系起来,从而确保它们有效地跨细胞膜运输。然而,在NCBTs运输CO32−的情况下,我们假设膜相关CAs的作用不是产生或消耗底物,而是使膜附近纳米结构域的pH变化最小化。
Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO2) and water into bicarbonate (HCO3−) and protons (H+), thereby influencing pH, are near the core of virtually all physiological processes in the body. In the kidneys, soluble and membrane-associated CAs and their synergy with acid–base transporters play important roles in urinary acid secretion, the largest component of which is the reabsorption of HCO3− in specific nephron segments. Among these transporters are the Na+-coupled HCO3− transporters (NCBTs) and the Cl−-HCO3− exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO3−“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO32− rather than HCO3− and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO3−” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO3− reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO2, HCO3−, and H+) and thus ensuring their efficient transport across cell membranes. In the case of CO32− transport by NCBTs, however, we hypothesize that the role of membrane-associated CAs is not the appreciable production or consumption of substrates but the minimization of pH changes in nanodomains near the membrane.
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