Interactive sigmoidal O2 dissociation curve: Hill equation, P50, Bohr effect, cooperativity, and allosteric regulation of hemoglobin
Hemoglobin (Hb) is a tetrameric protein with four heme groups, each capable of binding one O2 molecule. As each O2 binds, conformational changes increase the affinity for subsequent O2 molecules — a phenomenon called cooperative binding. This produces the characteristic sigmoidal O2 dissociation curve, described by the Hill equation: Y = pO2^n / (P50^n + pO2^n), where Y is fractional saturation, P50 is the pO2 at 50% saturation, and n is the Hill coefficient measuring cooperativity.
The Bohr effect: decreased pH (increased H+) and increased CO2 shift the curve rightward, reducing O2 affinity and promoting O2 release in metabolically active tissues. Temperature increases also shift the curve right. 2,3-DPG (diphosphoglycerate), produced by red blood cells, binds deoxyhemoglobin and stabilizes the T-state, shifting the curve right. Fetal hemoglobin (HbF) has lower 2,3-DPG affinity, giving it higher O2 affinity (left shift) to extract O2 from maternal blood. Myoglobin, a monomeric protein, shows hyperbolic binding (n=1) with very high O2 affinity.
P50 is a key clinical parameter: normal adult P50 ≈ 26.6 mmHg. Right shift (higher P50) occurs in anemia, high altitude adaptation, increased 2,3-DPG, acidosis, and hyperthermia — facilitating O2 unloading to tissues. Left shift (lower P50) occurs in carbon monoxide poisoning, methemoglobinemia, hypothermia, alkalosis, and fetal blood — increasing O2 affinity but potentially impairing tissue delivery. Pulse oximetry uses the sigmoidal relationship to noninvasively estimate arterial O2 saturation.
Start with the Normal Adult preset to see the standard sigmoidal curve. Note the P50 value (≈26.6 mmHg) and Hill coefficient (≈2.8). When paused, moving sliders updates the control values first; press Run to apply them and start the pulse animation. Adjust pH downward to observe the Bohr effect — the curve shifts right. Switch to the Fetal Hb preset to compare its left-shifted curve. The Myoglobin preset shows a hyperbolic curve (n=1) without cooperativity and does not use hemoglobin-specific Bohr/2,3-DPG regulation in this model. The Hill Plot uses consistent log10 axes, so the slope corresponds to the Hill coefficient.