What amino acid substitution causes sickle cell anemia?

Sickle cell anemia is a genetic disorder caused by a specific mutation in the hemoglobin gene, leading to the production of abnormal hemoglobin known as hemoglobin S (HbS). This condition arises from the substitution of the amino acid valine for glutamic acid at the sixth position of the β-chain of hemoglobin.

In normal hemoglobin (hemoglobin A), glutamic acid, which is hydrophilic, is positioned at this critical site, contributing to its solubility in blood. However, when valine, a hydrophobic amino acid, is substituted for glutamic acid due to a mutation in the gene encoding the β-chain of hemoglobin, the characteristics of hemoglobin change. Valine’s hydrophobic nature promotes the aggregation of hemoglobin molecules, especially under low oxygen conditions, leading to the characteristic sickle-shaped red blood cells.

This structural change results in the adverse effects associated with sickle cell anemia, including hemolytic anemia, pain episodes, and complications throughout the body caused by reduced blood flow and blood vessel obstruction due to sickling. Understanding this specific amino acid substitution is crucial in elucidating the pathophysiology of the disease and developing treatments.