The missing hydrogen ion, part-1: Historical precedents vs. fundamental concepts

The purpose of this review and commentary was to provide an historical and evidence-based account of organic acids and the biochemical and organic chemistry evidence for why cells do not produce metabolites that are acids. The scientific study of acids has a long history dating to the 16th and 17th centuries, and the definition of an acid was proposed in 1884 as a molecule that when in an aqueous solution releases a hydrogen ion (H+). There are three common ionizable functional groups for molecules classified as acids: 1) the carboxyl group, 2) the phosphoryl group and 3) the amine group. The propensity by which a cation will associate or dissociate with a negatively charged atom is quantified by the equilibrium constant (Keq) of the dissociation constant (Kd) of the ionization (Keq = Kd), which for lactic acid (HLa) vs. lactate (La-) is expressed as: Keq = Kd = [H+] [La-]=[HLa] = 4 677.351 4 (ionic strength = 0.01 Mol & sdot;L-1, T = 25 degrees C). The negative log10 of the dissociation pKd reveals the pH at which half of the molecules are ionized, which for HLa = 3.67. Thus, knowing the pKd and the pH of the solution at question will reveal the extent of the ionization vs. acidification of molecules that are classified as acids.