Haemoglobin F (HbF, α2γ2) has higher oxygen affinity than HbA (α2β2). Which biochemical property of HbF explains its fetal advantage in oxygen extraction from maternal blood?

• A HbF has a more acidic Bohr effect, releasing more oxygen at lower pH
• B HbF contains iron in a higher oxidation state (Fe3+) that binds oxygen more tightly
• C HbF's gamma chains bind 2,3-BPG less avidly than beta chains, maintaining HbF in higher oxygen affinity (R-state), allowing it to extract oxygen from HbA across the placenta ✓
• D HbF has a larger Bohr effect, releasing CO2 more efficiently at the placenta

Explanation

2,3-bisphosphoglycerate (2,3-BPG) stabilises the T-state (deoxyhaemoglobin) by binding in the central cavity between beta chains. HbF's gamma chains have a serine residue at position 143 (instead of histidine in beta chains) that prevents optimal 2,3-BPG binding. Consequently, HbF binds 2,3-BPG poorly, remaining in the R-state (oxyhaemoglobin) at lower oxygen tensions compared to HbA. At the placenta, maternal HbA releases oxygen (shifted to T-state by 2,3-BPG) while fetal HbF, with its higher affinity, extracts it — creating an oxygen tension gradient that drives transfer from mother to fetus. In sickle cell anaemia, elevated fetal HbF reduces sickling.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.