Intact carbonic acid is a viable protonating agent for biological bases

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 pK_as 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 pK_a(CA), pK_a(T) = −373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pK_a(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.