Invited review: Quantifying proton exchange from chemical reactions - Implications for the biochemistry of metabolic acidosis.
Level 5 - mechanism / opinion, no new human data
Mechanism-based reasoning and computational biochemical modeling without empirical human trial data.
PubMed 31071454 · doi:10.1016/j.cbpa.2019.04.024
What was done
This review and theoretical modeling paper evaluated pH-dependent competitive cation fractional proton exchange (~H+e) in metabolic reactions. The author developed a computational model of substrate flux in skeletal muscle during intense exercise and combined these flux estimates with stoichiometric data from non-mitochondrial energy catabolism to quantify net proton release and consumption across metabolic pathways.
What was found
Totality of cytosolic energy catabolism was calculated to result in a net proton release of -187.2 mmol/L. Total glycolytic proton exchange contributed -85.0 mmol/L, and ATP hydrolysis contributed -43.1 mmol/L. Lactate production provided the largest metabolic proton buffering effect by consuming protons (+44.5 mmol/L). The calculated ratio of total proton release to lactate accumulation was 4.25.
Why it matters
These calculations detail the chemical sources of proton accumulation during cellular catabolism, providing biochemical evidence that lactate production acts as a proton consumer rather than the primary cause of metabolic acidosis.
Limits
The findings are derived from mathematical and biochemical modeling rather than direct in vivo measurements in human participants. The model relies on assumed skeletal muscle substrate flux conditions and does not capture whole-body systemic physiological interactions.
Cited by
- supports Glycolysis produces lactate rather than lactic acid, and exercise acidosis is caused by protons liberated from ATP hydrolysis.