Sickle cell anemia is a form of sickle cell disease, a disorder that affects red blood cells. Normal red blood cells resemble a disc with concave surfaces on both sides that increase the surface area of the cell. If you have sickle cell anemia, you develop abnormally shaped red blood cells that resemble curved sickle blades. These abnormal cells cannot function properly. Inherited mutations play a role in sickle cell anemia by causing abnormal protein folding that drives the progression of the disease.
Genetics
The protein-folding disruption that occurs in sickle cell anemia is due to inherited mutations in the gene that controls the protein hemoglobin, a component of red blood cells. Normally, hemoglobin contains two subunits, alpha and beta, and each complete hemoglobin molecule contains two copies of each subunit. The genetic mutation affects the beta subunit of hemoglobin and leads to a change in the amino acid sequence of the protein. If you inherit one mutant gene, you are a carrier for the sickle cell trait; if you inherit two, you develop sickle cell anemia. The genetic condition is most prevalent in individuals of African or Indian descent, according to Harvard University.
Effect on Protein Shape
The inherited genetic mutation in sickle cell anemia plays a role in the folding and structure of hemoglobin. If you have sickle cell anemia, you have an altered hemoglobin composition: the sixth amino acid of the beta subunit is valine instead of the glutamic acid found in those without the sickle cell trait. Valine and glutamic acid have very distinct chemical properties, and this substitution disturbs the normal chemical interactions that maintain the shape of hemoglobin. As a result, the mutant hemoglobin molecules twist and interact with other mutant hemoglobin to form abnormal aggregations of proteins that disrupt cellular functioning.
Effect on Red Blood Cells
The abnormal folding and protein aggregation that occurs in sickle cell anemia profoundly affects the shape of your red blood cells. The National Heart, Lung and Blood Institute explains that abnormal aggregations of mutant hemoglobin act like scaffolds within the cell, with long protein strands pushing the cell into the characteristic sickle shape. The abnormal sickle cells are unable to function normally and may also block blood flow through your blood vessels, leading to a range of health problems, including stroke or erectile dysfunction, according to the University of Maryland Medical Center.
Treatment
Although no cure is available for sickle cell anemia, exploiting the protein folding disruptions that occur in the disease may be the key to treating this disorder in the future. Harvard University explains that the chemical interactions that bond mutated hemoglobin molecules together are fairly weak. As a result, drugs could target these chemical interactions, disrupting the formation of mutant hemoglobin strands and scaffolds that cause the sickle cell shape.
