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

Review

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

Robert A Robergs. Comp Biochem Physiol A Mol Integr Physiol. 2019 Sep.

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.

Similar articles

• Competitive cation binding computations of proton balance for reactions of the phosphagen and glycolytic energy systems within skeletal muscle.

  Robergs RA. Robergs RA. PLoS One. 2017 Dec 21;12(12):e0189822. doi: 10.1371/journal.pone.0189822. eCollection 2017. PLoS One. 2017. PMID: 29267370 Free PMC article.

• [The Stewart model. "Modern" approach to the interpretation of the acid-base metabolism].

  Rehm M, Conzen PF, Peter K, Finsterer U. Rehm M, et al. Anaesthesist. 2004 Apr;53(4):347-57. doi: 10.1007/s00101-004-0660-x. Anaesthesist. 2004. PMID: 15088097 Review. German.

• The meaning of acid-base abnormalities in the intensive care unit: part III -- effects of fluid administration.

  Morgan TJ. Morgan TJ. Crit Care. 2005 Apr;9(2):204-11. doi: 10.1186/cc2946. Epub 2004 Sep 3. Crit Care. 2005. PMID: 15774079 Free PMC article. Review.

• Biochemistry of exercise-induced metabolic acidosis.

  Robergs RA, Ghiasvand F, Parker D. Robergs RA, et al. Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R502-16. doi: 10.1152/ajpregu.00114.2004. Am J Physiol Regul Integr Comp Physiol. 2004. PMID: 15308499 Review.

Cited by

• The tortuous path of lactate shuttle discovery: From cinders and boards to the lab and ICU.

  Brooks GA. Brooks GA. J Sport Health Sci. 2020 Sep;9(5):446-460. doi: 10.1016/j.jshs.2020.02.006. Epub 2020 Feb 21. J Sport Health Sci. 2020. PMID: 32444344 Free PMC article. Review.

• The missing hydrogen ion, part-2: Where the evidence leads to.

  Robergs R, O'Malley B, Torrens S, Siegler J. Robergs R, et al. Sports Med Health Sci. 2024 Jan 15;6(1):94-100. doi: 10.1016/j.smhs.2024.01.001. eCollection 2024 Mar. Sports Med Health Sci. 2024. PMID: 38463661 Free PMC article. Review.

• Disuse-Induced Muscle Fatigue: Facts and Assumptions.

  Sergeeva XV, Lvova ID, Sharlo KA. Sergeeva XV, et al. Int J Mol Sci. 2024 May 3;25(9):4984. doi: 10.3390/ijms25094984. Int J Mol Sci. 2024. PMID: 38732203 Free PMC article. Review.

• The "Anaerobic Threshold" Concept Is Not Valid in Physiology and Medicine.

  Brooks GA. Brooks GA. Med Sci Sports Exerc. 2021 May 1;53(5):1093-1096. doi: 10.1249/MSS.0000000000002549. Med Sci Sports Exerc. 2021. PMID: 33844671 Free PMC article. No abstract available.

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

  Robergs R, O'Malley B, Torrens S, Siegler J. Robergs R, et al. Sports Med Health Sci. 2023 Nov 10;5(4):336-343. doi: 10.1016/j.smhs.2023.10.008. eCollection 2023 Dec. Sports Med Health Sci. 2023. PMID: 38314048 Free PMC article. Review.

Publication types

MeSH terms

Substances