Describe the Rapoport–Luebering shunt and the significance of 2,3-BPG.

Definition

The Pathway

1,3-bisphosphoglycerate → Bisphosphoglycerate mutase → 2,3-bisphosphoglycerate → 2,3-BPG phosphatase → 3-phosphoglycerate → Rejoins glycolysis

• The ATP normally made at the phosphoglycerate kinase step is sacrificed — the shunt yields no ATP
• About 15–25% of glycolytic flux in the RBC takes this route
• RBC 2,3-BPG concentration is high — roughly equimolar with haemoglobin (about 5 mmol/L)

Function of 2,3-BPG

• Binds to the central cavity of deoxyhaemoglobin, between the two β chains
• Stabilises the T (tense, low affinity) state
• Shifts the oxygen dissociation curve to the right → ↑ P50 → oxygen is unloaded more readily to the tissues
• Without 2,3-BPG, haemoglobin would bind oxygen so tightly that little would be released

Conditions Altering 2,3-BPG

Applied Aspects

• Stored blood loses 2,3-BPG within 1–2 weeks → the transfused cells hold oxygen tightly and release it poorly. Levels recover in 12–24 hours in the recipient. This matters in massive transfusion
• CPD-A anticoagulant contains adenine and dextrose partly to preserve 2,3-BPG and ATP
• Pyruvate kinase deficiency — the block is after the shunt, so 2,3-BPG accumulates → better tissue oxygenation → the anaemia is better tolerated than its severity suggests
• Adaptation to altitude — a rise in 2,3-BPG within hours is one of the earliest compensations