Hemoglobin S polymerizes under deoxygenated conditions because of which molecular change compared to normal hemoglobin A?

• A Lysine at position 6 of the alpha-globin chain is replaced by glutamic acid
• B A stop codon mutation leads to a truncated beta-globin chain
• C A splice-site mutation produces an unstable beta-globin that aggregates
• D Glutamic acid at position 6 of the beta-globin chain is replaced by valine, creating a hydrophobic patch ✓

Explanation

Sickle cell disease results from a GAG→GTG point mutation at codon 6 of the HBB gene, substituting valine (nonpolar) for glutamic acid (charged). In the deoxygenated state, the valine at position 6 fits into a hydrophobic pocket on an adjacent beta-chain, triggering HbS polymerization and RBC sickling. This is a gain-of-function structural defect, not a quantitative deficiency.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.