Fetal haemoglobin (HbF, α2γ2) has higher oxygen affinity than adult HbA (α2β2). The molecular basis of this difference is:

• A Gamma chains of HbF bind 2,3-BPG with less affinity than beta chains of HbA, because gamma chains lack key basic residues at the 2,3-BPG binding site ✓
• B HbF has higher affinity for CO2 in the Haldane effect
• C HbF forms tetramers with higher cooperativity and Hill coefficient
• D Gamma chains have higher heme iron Fe2+ stability preventing methemoglobin formation

Explanation

2,3-BPG binds in the central cavity of deoxyhaemoglobin, specifically interacting with beta chain residues (beta His143, beta His2, beta Lys82, beta N-terminal). This binding stabilises the T-state (deoxy), reducing O2 affinity. Fetal gamma chains have Ser at position 143 (instead of His in beta chains) and lack other basic residues, resulting in weaker 2,3-BPG binding. Because HbF binds less 2,3-BPG, it is less stabilised in the T-state and has higher O2 affinity. This allows HbF to effectively extract O2 from maternal HbA across the placenta. Cooperativity is similar between HbF and HbA. Haldane effect involves CO2 and haemoglobin but is not the basis of HbF/HbA affinity difference.

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

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Written and medically reviewed by the StethoPrep medical team.