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

• A HbF has a higher Hill coefficient (n), making it more cooperative in oxygen binding
• B HbF's gamma chains have reduced affinity for 2,3-DPG compared to beta chains in HbA, resulting in a left-shifted ODC ✓
• C HbF has a different heme group with higher iron oxidation state enabling tighter O2 binding
• D HbF binds CO2 more efficiently, freeing more sites for O2 binding

Explanation

Adult HbA (α2β2) beta chains bind 2,3-DPG (2,3-bisphosphoglycerate) avidly at specific sites (including His143β and Lys144β of each beta chain). 2,3-DPG stabilizes the deoxy (T-state) configuration of Hb, reducing O2 affinity and right-shifting the oxygen-dissociation curve (P50 ~27 mmHg for HbA). Fetal HbF (α2γ2) has gamma chains instead of beta chains; gamma chains have a serine at position 143 (instead of histidine), making them less able to bind 2,3-DPG. With reduced 2,3-DPG binding, HbF remains in the R-state (oxy form) at lower PO2, giving a left-shifted ODC (P50 ~19-20 mmHg) and facilitating O2 transfer from maternal HbA to fetal HbF at the placenta.

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

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