2,3-Diphosphoglycerate (2,3 DPG)

[Ref: JN5: p269-271]

2,3 DPG stands for 2,3-diphosphoglycerate
* aka bisphosphoglycerate (BPG)

 

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

 

[HH26:p45]

2,3 DPG binds to beta chains in deoxyHb
--> Stablizes deoxyHb
--> Allows Hb to give up O2 more readily
--> Thus decreasing O2 affinity, increasing p50 value

2,3 DPG binds more weakly to HbF
--> HbF has higher O2 affinity

2,3 DPG is extruded from Hb on oxygenation

Production of 2,3 DPG

Rapoport-Luebering shunt

[HH26:p140; JN5:p270]

In RBC, during glycolysis,

Production of 1 ATP may be bypassed by undergoing an alternative pathway
* Rapoport-Luebering shunt [PK1:p238]

1,3-Diphosphoglycerate ----> 2, 3 DPG
* by diphosphoglycerate mutase

2,3 DPG ----> 3-phosphoglycerate
* by diphosphoglycerate phosphatase

NB:

• At high pH, 2,3 DPG is increased because activities of DPG mutase is enhanced and DPG phosphatase is diminished
• Low pO2 promotes synthesis of 2,3 DPG in RBC

 

Clinical relevance of 2,3 DPG

Theoretically, 2,3-DPG level can change p50 from 15-34mmHg

However, research showed that effects in p50 due to 2,3DPG is likely to be of marginal significance in comparison with changes in arterial pO2, pH, tissue perfusion

Blood storage and transfusion

Also see Whole blood storage

In stored blood, RBC 2,3 DPG
* Diminishes in storage
* Effectively zero after 1-2 weeks of storage
* Rate of decline depends on preservative type

After transfusion
--> RBC 2,3 DPG returns to 50% after 7 hours, and to normal levels 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 26.6mmHg)

--> 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 (18-20mmHg)

 

Other notes