2,3-Bisphosphoglyceric acid  (2,3-BPG), also known  as 2,3-diphosphoglyceric acid (2,3-DPG).

2,3-BPG is present in human red blood cells at approximately 5 mmol/L. 

RBC’s have a level of 2,3-biphosphoglycerate that is 1000 times as as as the level in all other cells.

It binds with greater affinity to deoxygenated hemoglobin than it does to oxygenated hemoglobin due to conformational differences.

2,3-BPG is an intermediate in the glycolic pathway that binds specifically to deoxyhemoglobin and lowers its affinity for oxygen.

When hemoglobin is exposed to increasing oxygen pressure, the presence of 2,3-BPG low is the fractional oxygen saturation, and the oxygen binding curve is shifted to the right.

2,3-BPG has an estimated size of about 9 A and fits in the deoxygenated hemoglobin conformation (with an 11 angstroms pocket), but not as well in the oxygenated conformation (5 angstroms).

2,3 BPG interacts with deoxygenated hemoglobin beta subunits and so it decreases the affinity for oxygen and allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin.


2,3 BPG enhances the ability of RBCs to release oxygen near tissues that need it most. 

Nearly all patients with anemia, regardless of the cause have increased RBC 2,3-BPG levels: this adaptation greatly increases oxygen delivery.


2,3-BPG is an allosteric effector.


2,3-BPG is formed from 1,3-BPG by the enzyme BPG mutase. 


2,3-BPG  can be broken down by 2,3-BPG phosphatase to form 3-phosphoglycerate. 


The facility with which hemoglobin releases oxygen to the tissues is controlled by erythrocytic 2,3-diphosphoglycerate (2,3-DPG) such that an increase in the concentration of 2,3-DPG decreases oxygen affinity and vice versa. 


The increased oxygen affinity of blood stored in acid-citrate-dextrose (ACD) solution has been shown to be due to the decrease in the concentration of 2,3-DPG which occurs during storage. 


Hypophosphataemia in association with parenteral feeding reduces 2,3-DPG concentration and so increases oxygen affinity. 

Disorders of acid-base balance effect oxygen affinity not only by the direct effect of pH on the oxyhemoglobin dissociation curve but by its control of 2,3-DPG metabolism. 

Anaesthesia alters the position of the oxyhemoglobin dissociation curve.

Its synthesis and breakdown are, therefore, a way around a step of glycolysis, with the net expense of one ATP per molecule of 2,3-BPG generated as the high-energy carboxylic acid-phosphate mixed anhydride bond is cleaved by bisphosphoglycerate mutase.

There is a delicate balance between the need to generate ATP to support energy requirements for cell metabolism and the need to maintain appropriate oxygenation/deoxygenation status of hemoglobin.


When 2,3-BPG binds deoxyhemoglobin, it acts to stabilize the low oxygen affinity state of the oxygen carrier.

It fits into the cavity of the deoxy- conformation.



This position exploits the molecular symmetry and positive polarity by forming salt bridges with lysine and histidine residues in the ß subunits of hemoglobin. 


When oxygen is bound to a heme group, the R state, the 2,3-BPG has a different conformation and does not allow this interaction.


By itself, hemoglobin has sigmoid-like kinetics. 


By binding to deoxyhemoglobin, 2,3-BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues. 

The 2,3-BPG feedback loop that can help prevent tissue hypoxia in conditions where it is most likely to occur. 

In clinical conditions of low tissue oxygen concentration:  such as high altitude, airway obstruction, or congestive heart failure 2,3-BPG levels are higher and causes RBCs to generate more 2,3-BPG, as changes in pH and oxygen modulate the enzymes that make and degrade it.


As 2,3-BPG accumulates, it decreases the affinity of hemoglobin for oxygen, increasing oxygen release from RBCs under circumstances where it is needed most. 


The 2,3-BPG affect on hemoglobin is potentiated by the Bohr effect, in which hemoglobin’s binding affinity for oxygen is also reduced by a lower pH and high concentration of carbon dioxide. 


In pregnancy there is a 30% increase in intracellular 2,3-BPG, lowering the maternal hemoglobin affinity for oxygen, and allowing  more oxygen to be offloaded to the fetus.


The fetus has a low 2,3-BPG, so its hemoglobin has a higher affinity for oxygen, explaining the low pO2 in the uterine arteries, yet the fetal umbilical artery can still get oxygenated from them.


Fetal hemoglobin exhibits a low affinity for 2,3-BPG, resulting in a higher binding affinity for oxygen. 


Fetal hemoglobin has more affinity to oxygen than adult hemoglobin. 


Hyperthyroidism modulates in vivo 2,3-BPG content in erythrocytes by changes in the expression of phosphoglycerate mutase (PGM) and 2,3-BPG synthase, increasing the 2,3-BPG content of erythrocytes.


Erythrocytes increase their intracellular 2,3-BPG concentration by as much as five times within one to two hours in patients with chronic anemia.


The increased 2,3 BPG in RBCs occurs when the oxygen carrying capacity of the blood is diminished, resulting in a rightward shift of the oxygen dissociation curve and more oxygen being released to the tissues.


Low 2,3-BPG occurs with high altitude pulmonary edema at high altitudes.


Normal 2,3 DPG level in RBCs 5 Moles/L.


With hemodialysis mechanical stress on the erythrocytes is believed to cause the 2,3-BPG escape.


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