Intact carbonic acid is a viable protonating agent for biological bases

• Published in: Proceedings of the National Academy of Sciences
• Main Authors: Aminov, Daniel, Pines, Dina, Kiefer, Philip, Daschakraborty, Snehasis, Hynes, James, Pines, Ehud
• Other Authors: Ben-Gurion University of the Negev (BGU), Department of Chemistry and Biochemistry Boulder, University of Colorado Boulder, Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2019
• Subjects: Physical Sciences; carbonic acid; protonation of biological bases; biological buffers; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Carbonic acid
• Online Access: https://hal.sorbonne-universite.fr/hal-02967085; https://hal.sorbonne-universite.fr/hal-02967085/document; https://hal.sorbonne-universite.fr/hal-02967085/file/Aminov%20et%20al.%20-%202019%20-%20Intact%20carbonic%20acid%20is%20a%20viable%20protonating%20agent.pdf; https://doi.org/10.1073/pnas.1909498116

International audience Carbonic acid H2CO3 (CA) is a key constituent of the universal CA/bicarbonate/CO2 buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKas and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pKa(CA), pKa(T) = −373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pKa(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to H2O and CO2 does not impair its ability to act as an ordinary carboxylic acid and to efficiently protonate physiological-like bases. The consequences of this conclusion are far reaching for human physiology and marine biology. While CA is somewhat less reactive than (H+)aq, it is more than 1 order of magnitude more abundant than (H+)aq in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H+)aq in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H+)aq, often considered to be the major protonating agent there. CA should thus function as a major source for fast in vivo acid–base reactivity in the blood plasma, possibly penetrating intact into membranes and significantly helping to compensate for (H+)aq’s kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.