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 16^th and 17^th 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 (K_eq) of the dissociation constant (K_d) of the ionization (K_eq ​= ​K_d), which for lactic acid (HLa) vs. lactate (La^-) is expressed as: $K_{eq}=K_d=\frac{\left[H^{+}\right]\left[{La}^{-}\right]}{\left[HLa\right]}=$ 4 677.351 4 (ionic strength ​= ​0.01 Mol⋅L^-1, T ​= ​25 ​°C). The negative log₁₀ of the dissociation pK_d reveals the pH at which half of the molecules are ionized, which for HLa ​= ​3.67. Thus, knowing the pK_d and the pH of the solution at question will reveal the extent of the ionization vs. acidification of molecules that are classified as acids.