2,3-Diphosphoglycerate (2,3 DPG)

What is 2,3, DPG? How is it produced in the red blood cell and how does it interact with haemoglobin? What is its relevance in altitude exposure, stored blood and anaemia. (95A1) (1991)

 

Reference: Nunn p.269

 

• 2,3 DPG stands for 2,3-diphosphoglycerate

 

Function of 2,3 DPG

Binds to beta-chain of one tetramer of deoxyhaemoglobin, causes conformational change that reduces O2 affinity (displacing dissociation curve to the right).

=> Increased levels of 2,3 DPG

=> reduced the affinity of haemoglobin

=> Right shift of ODC

 

Production of 2,3 DPG

1,3-Diphosphoglycerate -> 2, 3 DPG

=> by diphosphoglycerate mutase

2,3 DPG -> 3-phosphoglycerate

=> by diphosphoglycerate phosphatase

 

At high pH, 2,3 DPG is increased because activities of DPG mutase is enhanced and DPG phosphatase is diminished.

 

Clinical relevance of 2,3 DPG

Blood storage and transfusion

Red cell 2,3 DPG in stored blood diminishes in storage and is effectively zero after 1-2 weeks

=> rate of decline depends on types of preservative used

After transfusion, red cell 2,3 DPG returns to 50% after 7 hours, and to normal level after 48 hours.

In theory, decreased 2,3 DPG can impair tissue oxygenation.

In reality, changes in P50 usually is less than 0.5kPa (or 3.8mmHg), and effect is quite minimal.

Anaemia

Anaemia results in a raised 2,3 DPG level.

=> Increased P50 to 30mmHg (from 27mmHg)

=> improve oxygen unloading in the tissues (by maintaining pressure gradient).

 

Altitude

Altitude causes an increased red cell concentration of 2,3 DPG.

But, progressive respiratory alkalosis due to altitude will have an opposite effect and much more pronounced.

Thus, ODC still shift to left despite increased 2,3 DPG.

Foetal haemoglobin

Foetal haemoglobin has 2 alpha chains and 2 gamma chains and no beta chains.

=> less sensitive to effect of 2,3 DPG

=> P50 lower

 

Additional notes

Examiner's comment

None.