1. What is the role of 2, 3-Bisphosphoglycerate (2,3-BPG) in the function of hemoglobin as an...

1. What is the role of 2, 3-Bisphosphoglycerate (2,3-BPG) in the function of hemoglobin as an oxygen carrier molecule? Explain the binding mechanism and effect of 2,3-BPG leading to the reduced oxygen binding affinity for hemoglobin and transitions in the T and R states of hemoglobin.

Expert Solution

Answer 1 :

Haemoglobin is primarily responsible for the delivery of oxygen from lungs to tissue sand transport of Carbon dioxide from tissues to lungs.

2, 3-Bisphosphoglycerate (2,3- BPG) is the most abundant organic phosphate in RBC's. Its molar concentration is approximately equivalent to that of haemoglobin. 2,3-BPG is produced in the erythrocytes from an intermediate of Glycolysis.

2,3-BPG regulates the binding of oxygen to haemoglobin. It specifically binds to deoxyhaemoglobin and decreases the oxygen affinity to haemoglobin. This reduced affinity facilitates release of oxygen in the tissues. One molecule of 2,3-BPG binds with one molecule of deoxyhaemoglobin in the central cavity of the 4 subunits (Haemoglobin is a tetramer).This central pocket has positively charged 2 beta globin chains. Ionic bonds also known salt bridges are formed between these positively charged Beta globin with negatively charged phosphate groups of 2,3-BPG. By cross-linking, the binding 2,3-BPG stabilizes the deoxygenated haemoglobin. This is the T form of haemoglobin. On oxygenation of haemoglobin, 2,3-BPG is expelled from this pocket converting the oxyhaemoglobin to its R form structure.

This small molecule i.e. 2,3-BPG has lot of biomedical significance :
- In Hypoxia, the concentration of 2,3-BPG in RBC's is elevated. This helps in acclimatization to high altitude and also helps in obstructive pulmonary Emphysema.
- 2,3-BPG level are increased in anaemia in order to cope with the high oxygen demand.
- When blood is stored in Citrate dextrose medium in blood banks, concentration of 2,3-BPG reduces. Such blood on transfusion fails to supply oxygen to tissues immediately. Addition of Inosine to stored blood prevents this reduction of 2,3-BPG.
- The binding of 2,3-BPG fetal haemoglobin is very weak and therefore, HbF has higher affinity for oxygen as compared to HBA and this is essential to transfer oxygen from maternal blood to the fetus.

gladiator answered 2 years ago

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