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Role of Carbonic Anhydrases and Inhibitors in Acid–Base Physiology: Insights from Mathematical Modeling

1
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
2
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
3
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3841; https://doi.org/10.3390/ijms20153841
Received: 26 June 2019 / Revised: 24 July 2019 / Accepted: 25 July 2019 / Published: 6 August 2019
(This article belongs to the Special Issue Protease and Carbonic Anhydrase Inhibitors, II)
Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3) and protons (H+). These enzymes impact numerous physiological processes that occur within and across the many compartments in the body. Within compartments, CAs promote rapid H+ buffering and thus the stability of pH-sensitive processes. Between compartments, CAs promote movements of H+, CO2, HCO3, and related species. This traffic is central to respiration, digestion, and whole-body/cellular pH regulation. Here, we focus on the role of mathematical modeling in understanding how CA enhances buffering as well as gradients that drive fluxes of CO2 and other solutes (facilitated diffusion). We also examine urinary acid secretion and the carriage of CO2 by the respiratory system. We propose that the broad physiological impact of CAs stem from three fundamental actions: promoting H+ buffering, enhancing H+ exchange between buffer systems, and facilitating diffusion. Mathematical modeling can be a powerful tool for: (1) clarifying the complex interdependencies among reaction, diffusion, and protein-mediated components of physiological processes; (2) formulating hypotheses and making predictions to be tested in wet-lab experiments; and (3) inferring data that are impossible to measure. View Full-Text
Keywords: CO2; pH; HCO3; facilitated diffusion; buffering; cell membranes; renal proximal tubules; red blood cells; alveoli; gas exchange CO2; pH; HCO3; facilitated diffusion; buffering; cell membranes; renal proximal tubules; red blood cells; alveoli; gas exchange
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Occhipinti, R.; Boron, W.F. Role of Carbonic Anhydrases and Inhibitors in Acid–Base Physiology: Insights from Mathematical Modeling. Int. J. Mol. Sci. 2019, 20, 3841.

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