Intact carbonic acid is a viable protonating agent for biological bases

Daniel Aminov, Dina Pines, Philip M. Kiefer, Snehasis Daschakraborty, James T. Hynes, Ehud Pines

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)20837-20843
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - 15 Oct 2019


  • Biological
  • Blood plasma
  • Carbonic acid
  • Protonation

ASJC Scopus subject areas

  • General


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