• 2,3-Diphosphoglycerate (2,3-DPG) is a special intermediate of glycolysis in erythrocytes which is rapidly consumed under conditions of normal oxygen tension. However, when hypoxia is encountered in peripheral tissues, the concentration of 2,3-DPG can accumulate to significant levels within hours. At these concentrations, 2,3-DPG can bind to hemoglobin and reduce its affinity for oxygen, resulting in a right-ward shift of the Oxygen-Hemoglobin Dissociation Curve discussed in Oxygen Transport. This results in enhanced unloading of oxygen by hemoglobin and thus results in enhanced oxygen transport to tissues encountering long-term hypoxia.

Modulation of the Oxygen-Hemoglobin Dissociation Curve
A variety of environmental factors can shift the Oxygen-Hemoglobin Dissociation Curve. Effects which are associated with increased peripheral tissue metabolism, such as reduced pH, increased CO2, increased temperature, shift the curve to the right, reducing hemoglobin’s affinity for oxygen and thus improving oxygen unloading. Chronic hypoxia increases the blood’s concentration of 2,3-DPG which also shifts the curve to the right. The presence of HbF and carbon monoxide (CO) shift the curve to the left, increasing the oxygen affinity of hemoglobin.