Question

The drug hydroxyurea can be used to treat sickle cell anemia, although it is not often used because of undesirable side effects. Hydroxyurea is thought to function by stimulating the afflicted person’s synthesis of fetal hemoglobin. In a clinical study, patients who took hydroxyurea showed a 50% reduction in frequency of hospital admissions for severe pain, and there was also a decrease in the frequency of fever and abnormal chest X-rays. Why would this drug alleviate the symptoms of sickle cell anemia?

Answer 1

Hemoglobin occurs in two forms: deoxy form and oxy form. Deoxyhemoglobin contains glutamic acid (glu) at the sixth position of its β-chain. In sickle cell anemia, this glu is replaced by valine which interacts with the hydrophobic part of another chain. This interaction leads to polymerisation of deoxyhemoglobin and results in sickling of cell. As these cells are unable to pass through the capillaries, it leads to reduced blood flow and death of tissues.

Hydroxyurea increases the fraction of cells containing fetal hemoglobin. In fetal Hb, there exists a γ- chain in which sickle cell hemoglobin(hemoglobin S) is absent. That is, in fetal Hb, such polymerisation does not occur which leads to a normal blood flow.

By increasing the concentration of fetal Hb, hydroxyurea dilutes the defective hemoglobin-S and makes it difficult to polymerisation and reduce the blood flow.