The Bohr/Haldane effect: a model-based uncovering of the full extent of its impact on O 2 delivery to and CO 2 removal from tissues.
Level 5 - mechanism / opinion, no new human data
Mechanism-based theoretical and mathematical modeling study with no empirical human data.
PubMed 29745803 · doi:10.1152/japplphysiol.00140.2018
What was done
A theoretical simulation was conducted using a two-ligand, two-state mathematical model to evaluate simultaneous oxygen and proton binding to hemoglobin and associated acid-base changes in surrounding solution. The model evaluated the effect of varying the number of active Bohr groups from 0 to 8 per hemoglobin tetramer at a constant carbon dioxide partial pressure (Pco2) of 40 mmHg to assess the relationship between the Bohr factor and hemoglobin oxygen affinity (P50).
What was found
Varying the number of Bohr groups per hemoglobin tetramer from 0 to 8 increased the Bohr factor from 0 to -0.9 and increased P50 from 6 to 46 mmHg at a constant Pco2 of 40 mmHg. Blocking the Bohr effect in the model increased hemoglobin oxygen affinity (lowering P50), indicating that P50 and the Bohr factor are directly related.
Why it matters
This theoretical work suggests that the Bohr effect is primarily responsible for setting hemoglobin oxygen affinity and facilitating tissue oxygen unloading, challenging the classical view that its primary physiological role is in carbon dioxide removal.
Limits
The findings are derived entirely from a mathematical simulation without new empirical, in vitro, or in vivo biological measurements. The simplified two-state biophysical model does not account for complex physiological factors such as red blood cell transit dynamics, membrane transport kinetics, or allosteric modulators beyond protons and carbon dioxide.
Cited by
- supports An excess of carbon dioxide increases body acidity, which decreases the binding affinity between hemoglobin and oxygen.