Fetal haemoglobin (HbF) has a higher oxygen affinity than adult HbA. At physiological pH, the P50 of HbF is approximately 18–20 mmHg versus 26–27 mmHg for HbA. Which molecular feature primarily accounts for this difference?

• A HbF has higher concentration of intracellular carbonic anhydrase, enhancing O2 loading
• B HbF has alpha and gamma chains; gamma chains bind 2,3-BPG less avidly than beta chains ✓
• C HbF binds CO2 more avidly, shifting its O2 dissociation curve leftward
• D HbF exists as a tetramer with 2 alpha + 2 delta chains that resist deoxygenation

Explanation

HbF consists of 2 alpha and 2 gamma chains (α2γ2). The gamma subunit differs from the adult beta subunit at position 143, where serine replaces a histidine residue that is the principal binding site for 2,3-bisphosphoglycerate (2,3-BPG). Because HbF binds 2,3-BPG poorly, it is not as easily shifted to the deoxy (T) state, maintaining high affinity for O2. This is physiologically essential: the fetal P50 of ~18 mmHg ensures O2 transfer from maternal HbA (P50 ~27 mmHg) across the placenta via the Bohr shift.

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

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