Haemoglobin S (HbS) polymerises on deoxygenation. The single amino acid substitution responsible is:

• A Glu → Lys at position 6 of the beta chain
• B His → Tyr at position 92 of the alpha chain (M-haemoglobin mutation)
• C Glu → Gly at position 26 of the beta chain (HbE)
• D Glu → Val at position 6 of the beta chain ✓

Explanation

Sickle cell disease (HbS) results from a single nucleotide substitution in the HBB gene (GAG→GTG) encoding the beta-globin chain, changing glutamic acid (Glu, negatively charged, hydrophilic) to valine (Val, uncharged, hydrophobic) at position 6. On deoxygenation, the hydrophobic valine at beta6 fits into a hydrophobic complementary site on the EF corner of the adjacent beta-globin chain, initiating HbS polymer formation. Glu→Lys would substitute a negatively charged residue with a positively charged residue but does not cause sickle cell disease. HbM mutations affect the iron redox state. HbE has Glu→Lys at beta26 and causes a mild thalassaemia-like phenotype.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.