What structural change occurs in sickle cell anemia?

In sickle cell anemia, a specific mutation in the gene coding for the beta chain of hemoglobin results in a notable structural change. This mutation involves the substitution of a single amino acid in the hemoglobin protein, where the hydrophilic amino acid glutamic acid is replaced by the hydrophobic amino acid valine at the sixth position of the beta-globin chain. This hydrophilic to hydrophobic switch causes the hemoglobin molecules to stick together in low-oxygen conditions, forming rigid structures that distort red blood cells into a sickle shape, impairing their flexibility and leading to various complications associated with the disease.

The change from a hydrophilic to a hydrophobic amino acid is critical for understanding the pathophysiology of sickle cell anemia because it underlies the abnormal aggregation of hemoglobin that characterizes the disorder. This explains the resultant drastic impact on erythrocyte morphology and function, which is central to the clinical manifestations experienced by individuals with the disease.