Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney
Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO<sub>2</sub>) and water into bicarbonate (HCO<sub>3</sub><sup>−</sup>) and protons (H<sup>+</sup>), thereby influencing pH, are near the core of virtually all phy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/4251 |
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| author | Seong-Ki Lee Walter F. Boron Rossana Occhipinti |
| author_facet | Seong-Ki Lee Walter F. Boron Rossana Occhipinti |
| author_sort | Seong-Ki Lee |
| collection | DOAJ |
| description | Carbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO<sub>2</sub>) and water into bicarbonate (HCO<sub>3</sub><sup>−</sup>) and protons (H<sup>+</sup>), 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 HCO<sub>3</sub><sup>−</sup> in specific nephron segments. Among these transporters are the Na<sup>+</sup>-coupled HCO<sub>3</sub><sup>−</sup> transporters (NCBTs) and the Cl<sup>−</sup>-HCO<sub>3</sub><sup>−</sup> exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO<sub>3</sub><sup>−</sup>“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO<sub>3</sub><sup>2−</sup> rather than HCO<sub>3</sub><sup>−</sup> and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO<sub>3</sub><sup>−</sup>” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO<sub>3</sub><sup>−</sup> reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO<sub>2</sub>, HCO<sub>3</sub><sup>−</sup>, and H<sup>+</sup>) and thus ensuring their efficient transport across cell membranes. In the case of CO<sub>3</sub><sup>2−</sup> 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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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:39:39Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-66a3bac128be4f91ba85eb3b0685c3df2023-11-16T21:11:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244425110.3390/ijms24044251Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the KidneySeong-Ki Lee0Walter F. Boron1Rossana Occhipinti2Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USACarbonic anhydrases (CAs), because they catalyze the interconversion of carbon dioxide (CO<sub>2</sub>) and water into bicarbonate (HCO<sub>3</sub><sup>−</sup>) and protons (H<sup>+</sup>), 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 HCO<sub>3</sub><sup>−</sup> in specific nephron segments. Among these transporters are the Na<sup>+</sup>-coupled HCO<sub>3</sub><sup>−</sup> transporters (NCBTs) and the Cl<sup>−</sup>-HCO<sub>3</sub><sup>−</sup> exchangers (AEs)—members of the “solute-linked carrier” 4 (SLC4) family. All of these transporters have traditionally been regarded as “HCO<sub>3</sub><sup>−</sup>“ transporters. However, recently our group has demonstrated that two of the NCBTs carry CO<sub>3</sub><sup>2−</sup> rather than HCO<sub>3</sub><sup>−</sup> and has hypothesized that all NCBTs follow suit. In this review, we examine current knowledge on the role of CAs and “HCO<sub>3</sub><sup>−</sup>” transporters of the SLC4 family in renal acid–base physiology and discuss how our recent findings impact renal acid secretion, including HCO<sub>3</sub><sup>−</sup> reabsorption. Traditionally, investigators have associated CAs with producing or consuming solutes (CO<sub>2</sub>, HCO<sub>3</sub><sup>−</sup>, and H<sup>+</sup>) and thus ensuring their efficient transport across cell membranes. In the case of CO<sub>3</sub><sup>2−</sup> 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.https://www.mdpi.com/1422-0067/24/4/4251transporterscarbonatebicarbonateacid–base homeostasiscell membranesrenal tubules |
| spellingShingle | Seong-Ki Lee Walter F. Boron Rossana Occhipinti Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney International Journal of Molecular Sciences transporters carbonate bicarbonate acid–base homeostasis cell membranes renal tubules |
| title | Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney |
| title_full | Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney |
| title_fullStr | Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney |
| title_full_unstemmed | Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney |
| title_short | Potential Novel Role of Membrane-Associated Carbonic Anhydrases in the Kidney |
| title_sort | potential novel role of membrane associated carbonic anhydrases in the kidney |
| topic | transporters carbonate bicarbonate acid–base homeostasis cell membranes renal tubules |
| url | https://www.mdpi.com/1422-0067/24/4/4251 |
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