Physiology · Respiratory Physiology (Mechanics, Gas Exchange, PFTs, Regulation)

In the oxygen-haemoglobin dissociation curve, 2,3-bisphosphoglycerate (2,3-BPG) reduces haemoglobin's O₂ affinity by:

  • A Covalently modifying a histidine residue on the alpha subunit, shifting allosteric equilibrium
  • B Competing with CO₂ for the same binding site on the beta subunit N-terminus
  • C Binding to the central cavity of deoxyhaemoglobin and stabilising the T (tense) conformation
  • D Increasing cooperativity between haem groups by altering haem-haem interactions
Correct answer: C. Binding to the central cavity of deoxyhaemoglobin and stabilising the T (tense) conformation

Explanation

2,3-BPG is a polyanion that binds within the central cavity of the deoxy (T-state) haemoglobin tetramer, making electrostatic interactions with positively charged residues on the beta chains (Val-1, His-2, Lys-82, His-143). This preferentially stabilises the T conformation, increasing the energy required for the R (oxy) transition and thereby shifting the O₂-Hb dissociation curve rightward (decreased O₂ affinity, increased P50). Fetal Hb (HbF) with gamma chains has weaker 2,3-BPG binding, explaining its higher O₂ affinity. CO₂ binds as carbamino compounds to N-terminal amino groups, not the same site as 2,3-BPG.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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