23 Jul WHY WOULD INCREASING THE SYNTHESIS OF FETAL HEMOGLOBIN RESULT IN ALLEVIATING THE SYMPTOMS OF SICKLE CELL ANEMIA?
You recall reading in the medical literature about a dramatic new drug treatment for sickle cell ane Show more You recall reading in the medical literature about a dramatic new drug treatment for sickle cell anemia and you?d like to try it on this patient. The drug is hydroxyurea and is thought to function by stimulating the afflicted person?s synthesis of fetal hemoglobin. Exactly how hydroxyurea stimulated fetal hemoglobin synthesis is unclear but it is believed that hydroxyurea is metabolized to NO which binds to a soluble guanylate cyclase enzyme which then catalyzes the synthesis of a second messenger cyclic GMP (cGMP). The cGMP interacts with transcription factors in a manner that is not completely understood to induce the transcription (and then translation) of the fetal hemoglobin gene. a. 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 increasing the synthesis of fetal hemoglobin result in alleviating the symptoms of sickle cell anemia? b. Medical practioners who used hydroxyurea as a treatment for sickle cell anemia noted that their patients seemed to benefit from the administration of the drug long before the synthesis of fetal hemoglobin had time to take effect. It has recently been determined that hydroxyurea can react directly with the iron ion of oxy- and deoxyHb to form iron nitrosyl hemoglobin (HbNO). Why would this be of benefit to the sickle-cell anemic patient? c. And finally hydroxyurea has been shown to produce NO directly in less than an hour after hydroxyurea administration. It?s also possible that HbNO could produce NO either directly or indirectly. NO is an important second messenger which even in nanomolar amounts stimulates vasodilation. How could NO production help the sickle-cell anemic patient? Show less
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