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.

For a century, the influence of the Bohr effect on the utilization of blood-borne oxygen has been deemed secondary to its influence on the uptake of carbon dioxide by the blood. Here, we show that the opposite is the case. Using a simple two-ligand, two-state formulation, we modeled the simultaneous oxygen and proton binding to hemoglobin, as well as the resulting acid-base changes of the surrounding solution. Blocking of the Bohr effect in this model system results in a dramatic increase in the oxygen affinity, as expressed by the oxygen partial pressure at half saturation, the P50 . It also becomes clear that the P50 and the Bohr factor (a measure of the size of the Bohr effect) are not independent but directly related. Thus, everything else being equal, varying the number of Bohr groups from 0 to 8 per tetramer results in an increase in the Bohr factor from 0 to -0.9 and an increase in P50 from 6 to 46 mmHg at a constant Pco2 of 40 mmHg. Therefore, changes in hemoglobin structure that lead to changes in the Bohr factor will inevitably also change hemoglobin oxygen affinity. NEW & NOTEWORTHY Using a mathematical model, we show that the Bohr effect has a more profound effect on gas exchange than is evident when comparing oxygen equilibrium curves measured in the laboratory at different constant values of Pco2 or pH. Protons preloaded on the Bohr groups, as well as the protons taken up during oxygen unloading, dramatically decrease oxygen affinity of the physiological oxygen equilibrium curve. Therefore, the Bohr effect is instrumental in setting the oxygen affinity.