What is the primary amino acid substitution that characterizes Sickle Cell Disease?

Sickle Cell Disease is primarily characterized by the substitution of glutamic acid with valine at the sixth position of the beta-globin chain of hemoglobin. This amino acid change is significant because glutamic acid is a hydrophilic, negatively charged amino acid, while valine is a hydrophobic, neutral amino acid. The presence of valine instead of glutamic acid alters the physicochemical properties of hemoglobin, leading to the polymerization of hemoglobin S (HbS) under low oxygen conditions. This polymerization causes the red blood cells to deform into a sickle shape, which is the hallmark of the disease and leads to various complications such as vaso-occlusive crises, pain, and organ damage. Understanding this specific amino acid substitution is crucial as it directly relates to the pathophysiology of Sickle Cell Disease.