3-BPG

Meaning: 2,3-Bisphosphoglycerate is a small, highly negatively charged molecule made in red blood cells from a glycolytic intermediate. It binds in the central cavity between the two β subunits of deoxyhemoglobin, where positively charged residues attract its phosphate groups. This stabilizes the tense (T) state, so hemoglobin's affinity for O₂ falls and the curve shifts right. It is a heterotropic allosteric effector, like H⁺ and CO₂. Its level rises in chronic hypoxia, such as at high altitude.

On the MCAT: Passages show oxygen-dissociation curves and ask which way a curve moves with more BPG, high altitude, or fetal hemoglobin. Right shift means higher P50, lower affinity and easier unloading in tissues. Fetal hemoglobin (α₂γ₂) binds BPG weakly, so it has higher O₂ affinity than adult hemoglobin (curve to the left), which favors O₂ transfer from maternal to fetal blood.

Common confusion: 1,3-BPG is a different molecule, a glycolysis intermediate that donates a phosphate to ADP. Also, BPG does not bind at the heme O₂ site, so it is not a competitive inhibitor of O₂ binding; it binds elsewhere and favors the T state. The curve stays sigmoidal, and in the lungs, where PO₂ is high, hemoglobin still loads close to full saturation.