Rapoport Leubering Cycle or Shunt (Synthesis of 2,3-bisphosphoglycerate)

Rapoport Leubering Cycle or Shunt

(Synthesis of 2,3-bisphosphoglycerate)

• This is a supplementary pathway to glycolysis which is operative in the erythrocytes of man and other mammals.
• Rapoport-Leubering cycle is mainly concerned with the synthesis of 2,3- bisphosphoglycerate (2,3-BPG)in the RBC.
• So, it maintains a high steady-state concentration of 2,3-biphosphoglycerate (2,3-BPG), produced by a diversion in glycolytic pathway.

Steps in Rapoport leubering cycle

• 1,3- Bisphosphoglycerate(1,3-BPG) produced in glycolysis is converted to 2,3-BPC by the enzyme 2,3-bisphosphoglycerate mutase.
• 2,3-BPC is hydrolyzed to 3-phosphoglycerate by bisphosphoglycerate phosphatase.
• It is now believed that bisphosphoglycerate mutase is a bifunctional enzyme with mutase and phosphatase activities catalyzed by two different sites present on the same enzyme.
• About 15-25% of the glucose that gets converted to lactate in erythrocytes goes via 2,3- BPG synthesis.

Fig.  Rapoport-Leubering cycle for the synthesis of 2,3-bisphosphoglycerate (2,3-BPG).

Significance of 2,3-BPG

• Factors which waste energy are not present in RBC
  • Energy demanding endergonic reactions utilizing ATP is not present in mature human red blood cells.
  • ATPase activity which controls ATP/ADP ratio is not active in mature RB Cells.
  • Production of 2,3-BPG allows glycolysis to proceed without the synthesis of ATP.
  • This is advantageous to erythrocytes since glycolysis occurs when the need for ATP is minimal.
  •  Rapoport-Leubering cycle is, therefore, regarded as a shunt pathway of glycolysis to dissipate or waste the energy not needed by erythrocytes.
• Role in haemoglobin(Hb):
  • 2,3-BPC is not a waste molecule in RBC. lt combines with hemoglobin(Hb) and reduces Hb affinity with oxygen.
  • Therefore, in the presence of 2,3-BPG, oxyhemoglobin unloads more oxygen to the tissues.
  • Adult Hb-A1: 2,3-BPG concentration is high, affinity to O2 less and unloading/dissociation is
    more.
  •  Hb-F: 2,3-BPG concentration is low, affinity to O2 is more, and unloading/dissociation is less.
• Role in hypoxia:
  • Increase in erythrocyte 2,3-BPG is observed in hypoxic conditions, high altitude, anemic conditions, etc.
  • In all these cases, 2,3- BPG will enhance the supply of oxygen to the tissues.
• Inherited enzyme deficiency:
  • Glycolysis in the erythrocytes is linked with 2,3-BPG production and oxygen transport.
  • In the deficiency of the enzyme hexokinase, glucose is not phosphorylated, hence the synthesis and concentration of 2,3-BPG are low in RBC.
  • The hemoglobin exhibits high oxygen affinity in hexokinase-defective patients.
  • On the other hand, in patients with pyruvate kinase deficiency, the level of 2,3-BPG in erythrocytes is high, resulting in low oxygen affinity.

References:

• https://en.wikipedia.org/wiki/Luebering%E2%80%93Rapoport_pathway
• https://biocyc.org/HUMAN/NEW-IMAGE?type=PATHWAY&object=PWY-6405
• https://medicoapps.org/m-rapoport-leubering-cycle/
• https://metacyc.org/META/new-image?type=PATHWAY&object=PWY-6405