What single amino acid substitution causes sickle cell anemia?

Sickle cell anemia is caused by a specific mutation in the hemoglobin gene that results in a single amino acid substitution. In this condition, the amino acid glutamic acid is replaced by valine at the sixth position of the beta-globin chain of hemoglobin. This substitution alters the properties of the hemoglobin molecule, leading to the formation of sickle-shaped red blood cells under low-oxygen conditions. This altered shape can cause blockages in blood vessels, leading to pain and other complications associated with the disease.

This specific change from glutamic acid to valine is crucial because glutamic acid is a relatively hydrophilic (water-attracting) amino acid, whereas valine is hydrophobic (water-repelling). The hydrophobic nature of valine leads to abnormal interactions between hemoglobin molecules, resulting in the sickling of red blood cells. Understanding this molecular basis is essential for grasping the pathophysiology of sickle cell disease and its clinical manifestations.