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

Abstract

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: Keq=Kd=[H+][La−][HLa]= 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.

Keywords

Hydrogen ion / Acid / Acidosis / pH / Equilibrium constant (K_eq) / Ionization / Dissociation constant (K_d)

Authors’ contributions

Robergs conceived the idea and researched the prior research evidence, wrote the manuscript and developed all tables and figures. Siegler, Torrens and O'Malley assisted in researching the prior research evidence, provided interpretations, assisted in the writing of the manuscript and completed proof reading and manuscript editing prior to submission.

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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