Sickle hemoglobin is associated with which amino acid substitution?

Sickle hemoglobin is primarily associated with the substitution of glutamic acid with valine at the sixth position of the beta-globin chain of hemoglobin. This specific amino acid change from glutamic acid, which is hydrophilic, to valine, which is hydrophobic, leads to a significant alteration in the properties of the hemoglobin molecule.

Valine's hydrophobic nature causes hemoglobin molecules to stick together under low oxygen conditions, forming long, rigid structures that distort red blood cells into a sickle shape. This sickling effect is responsible for the various clinical manifestations of sickle cell disease, including pain crises and increased risk of infection.

The correct response highlights the particular amino acid change that underlies the pathophysiology of sickle cell disease, providing critical insight into how a single mutation can lead to significant health implications.