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.