Q.27 Synthesis of 2.3-bisphosphoglycerate increases in high altitude because:
1. 2,3-bisphosphoglycerate favours the relaxed state of haemogobin
2. 2,3-bisphosphoglycerate serves as an energy source at high altitudes
3. 2.3-bisphosphoglycerate stabilizes the T-conformation of haemoglobin. thereby decreasing the oxygen
affinity of haemoglobin. making it more available to the peripheral tissues.
4. 2.3-bisphosphoglycerate regulates body temperature
Correct Answer: Option 3
2,3-Bisphosphoglycerate (2,3-BPG) synthesis increases at high altitudes to enhance oxygen delivery to tissues by modulating hemoglobin’s oxygen affinity.
Option Analysis
Option 1: Incorrect
2,3-BPG does not favor the relaxed (R) state of hemoglobin. Instead, it binds to and stabilizes the tense (T) state, which has lower oxygen affinity.
Option 2: Incorrect
2,3-BPG serves no role as an energy source. It is produced via the Rapoport-Luebering shunt in erythrocytes as a glycolysis byproduct, without generating ATP.
Option 3: Correct
At high altitudes, low oxygen partial pressure triggers hyperventilation and alkalosis, left-shifting the oxygen-hemoglobin curve. Increased 2,3-BPG stabilizes hemoglobin’s T-conformation, right-shifting the curve to decrease oxygen affinity, facilitating release to peripheral tissues despite reduced lung uptake.
Option 4: Incorrect
2,3-BPG has no known function in body temperature regulation. Its primary role is allosteric modulation of hemoglobin oxygen binding.
Introduction to 2,3-Bisphosphoglycerate High Altitude Adaptation
At high altitudes, lower atmospheric oxygen prompts the body to boost 2,3-bisphosphoglycerate (2,3-BPG) levels in red blood cells, aiding acclimatization. This molecule, formed in the Rapoport-Luebering shunt, binds deoxyhemoglobin’s central cavity, stabilizing the low-affinity T-state and right-shifting the oxygen dissociation curve.
Mechanism of Action
2,3-BPG decreases hemoglobin’s oxygen affinity by bridging β-chain residues in the T-conformation, unavailable in the R-state. At high altitude, hypoxia upregulates its synthesis within hours via elevated adenosine and AMPK activation of BPG mutase. This ensures tissues receive adequate oxygen despite lower pulmonary saturation.
Physiological Benefits
The adaptation yields a small lung uptake drop but amplifies tissue unloading, maintaining net oxygen delivery. Studies confirm rapid 2,3-BPG elevation at 5,260m, linked to genetic factors like RHCE expression.
| Factor | Effect on Hemoglobin | High Altitude Impact |
|---|---|---|
| T-State Stabilization | ↓ O₂ affinity | ↑ Tissue O₂ release |
| R-State | No binding | Unaffected |
| pH Alkalosis | Left-shift (countered) | Balanced by 2,3-BPG |
| Genetic RHCE | ↑ 2,3-BPG levels | Better acclimatization |
