Invited review: Quantifying proton exchange from chemical reactions - Implications for the biochemistry of metabolic acidosis

Abstract

Given that the chemistry of lactate production disproves the existence of a lactic acidosis, there is a need to further reveal and explain the importance of the organic and computational chemistry of pH dependent competitive cation fractional (~) proton (H⁺) exchange (~H⁺_e). An additional importance of this knowledge is that it could potentially contradict the assumption of the Stewart approach to the physico-chemical theory of acid-base balance. For example, Stewart proposed that chemical reaction and pH dependent H⁺ dissociation and association do not directly influence the pH of cellular and systemic body fluids. Yet at the time of Stewart's work, there were no data that quantified the H⁺ exchange during chemical reactions, or from pH dependent metabolite H⁺ association or dissociation. Consequently, the purpose of this review and commentary was three-fold; 1) to provide explanation of pH dependent competitive cation ~H⁺_e exchange; 2) develop a model of and calculate new data of substrate flux in skeletal muscle during intense exercise; and 3) then combine substrate flux data with the now known ~H⁺_e from chemical reactions of non-mitochondrial energy catabolism to quantify chemical reaction and metabolic pathway ~H⁺_e. The results of purpose 3 were that ~H⁺ release for the totality of cytosolic energy catabolism = -187.2 mmol·L^-1, where total glycolytic ~H⁺_te = -85.0 mmol·L^-1. ATP hydrolysis had a ~H⁺_te = -43.1 mmol·L^-1. Lactate production provided the largest metabolic ~H⁺ buffering with a ~H⁺_te = 44.5 mmol·L^-1. The total ~H⁺ release to La ratio = 4.25. The review content and research results of this manuscript should direct science towards new approaches to understanding the cause and source of H⁺_e during metabolic acidosis and alkalosis.

Keywords: ATP turnover; Cations; Creatine phosphate; Dissociation constant; Glycolysis.