Intact carbonic acid is a viable protonating agent for biological bases.

Carbonic acid HCO (CA) is a key constituent of the universal CA/bicarbonate/CO 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 pKs 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(CA), pK(T) = -373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pK(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to HO and CO 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), it is more than 1 order of magnitude more abundant than (H) in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H) in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H), 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)'s kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.