Bisphosphoglycerate

Bisphosphoglycerate, most commonly referring to 2,3-bisphosphoglycerate (2,3-BPG), is a metabolic intermediate produced in erythrocytes. It is derived from glyceraldehyde-3-phosphate through a branch of glycolysis known as the Rapoport-Luebering shunt and acts as an allosteric regulator of hemoglobin.

In red blood cells, 1,3-bisphosphoglycerate is converted to 2,3-bisphosphoglycerate by the enzyme bisphosphoglycerate mutase (BPGM). 2,3-BPG can then be hydrolyzed to 3-phosphoglycerate by 2,3-bisphosphoglycerate phosphatase, allowing glycolysis to continue. Some tissues use BPGM with both mutase and phosphatase activities; in others separate enzymes mediate the steps.

2,3-BPG binds preferentially to deoxygenated hemoglobin and stabilizes the T (tense) state, reducing hemoglobin’s affinity for oxygen. This shifts the hemoglobin oxygen dissociation curve to the right, promoting oxygen release in tissues. Fetal hemoglobin binds 2,3-BPG less effectively, contributing to its higher oxygen affinity.

Physiologically, erythrocyte 2,3-BPG levels increase with chronic hypoxia, anemia, and higher altitude, facilitating tissue oxygen delivery. Levels fall during blood storage and in conditions that favor glycolytic flux away from 2,3-BPG production. Abnormal 2,3-BPG levels can influence oxygen transport and are relevant in transfusion medicine and certain hemoglobinopathies.