Sickle cell disease is associated with a mutated form of hemoglobin (HbS) that aggregates to produce long rods within erythrocytes. Which of the following best explains how the mutation leads to aggregation of HbS?

Question

Quizplus · Accepted Answer

The mutation in sickle cell disease results in the substitution of valine for glutamic acid at the sixth position of the beta-chain, creating a hydrophobic patch that promotes aggregation.  HbS is the form of hemoglobin that results due to a missense mutation in the b-globin gene that causes sickle cell anemia. The mutation causing sickle cell anemia is a single nucleotide substitution (A-T) in the codon for amino acid 6. The change converts a glutamic acid codon (GAG) to a valine codon (GTG). Whereas, glutamate is an acidic and hydrophilic amino acid, leucine is hydrophobic. The presentation of this hydrophilic amino acid on the surface of the hemoglobin protein when in the deoxy state allows the proteins to aggregate via hydrophobic interactions. This aggregation leads to deformation of the erythrocyte, making it relatively inflexible and unable to traverse the capillary beds.

Sickle Cell Disease Is Associated with a Mutated Form of Hemoglobin