Question

People living at high altitude show an increased concentration of 2,3-BPG in red blood cells. What effect will the increased 2,3-BPG have on the oxygen binding curve of Hemoglobin? Draw and compare the Hemoglobin curves for sea=level altitude people and high-altitude people.

Answer 1

Ans. 2,3-bis phosphoglycerate: Mature RBC lacks membrane-bound organelles like nucleus, endoplasmic reticulum, mitochondria, etc. Absence of mitochondria also means that absence of cellular respiration pathways occurring in the organelles, including Citric Acid Cycle (CAC or TCA) and Electron Transport Chain (ETC). ETC is the terminal cellular pathways where O₂ is consumed to produce CO₂ simultaneously with harvesting energy from food in form of electrochemical gradient across mitochondrial inner membrane. So, RBC has glycolysis as the sole means of ATP production (net gain of 2 ATP per glycolysis) but no CAC and ETC.     

1,3-bisphosphoglycertae (1,3-BPG) is a glycolytic intermediate. 1,3-BPG is converted into 2,3-BPG by the enzyme bisphosphoglycertae mutase. The enzyme is exclusively expressed in RBCs and placenta. It exhibits optimum catalysis at pH 7.2, slightly lower than pH 7.4 of artery blood. During gaseous exchange between incoming capillaries and tissues, CO₂ diffuses into blood making it slightly acidic (due to activity of carbonic anhydrase). Simultaneously, 2,3-BPG binds to the beta subunit of HbA hemoglobin causes transition of R-state (HbO₂) into T-state (deoxyHb) by stabilizing T-state. Stabilization of T-sate by 2,3-BPG thus triggers dissociation of O₂ from HbO₂. [2,3-BPG] is around 5 mM in artery blood.

Higher [2,3-BPG], as observed in cases of hypoxia (depletion of O₂), Fe-deficiency anemia, hyperthyroidism and in people living at higher altitudes, cause right shift in HbO₂ dissociation curve leading to greater release of O₂ (thus, increases O₂-utilization coefficient of blood above normal value of 4.6 mL O₂/ dL blood). Lower [2,3-BPG] makes O₂ dislodging from oxyhemoglobin difficult by favoring R-state, thus shifts HbO₂dissociation curve to the left.