TY - JOUR
T1 - Time resolved absorption study of the reaction of hydroxyurea with sickle cell hemoglobin
AU - Kim-Shapiro, Daniel B.
AU - King, S. Bruce
AU - Bonifant, Challice L.
AU - Kolibash, Christopher P.
AU - Ballas, Samir K.
N1 - Funding Information:
We thank Yiren Gu for helpful discussion. This work was supported by Wake Forest University startup funds (DBK-S), the American Heart Association (grant 963031N awarded to SBK) and the National Institutes of Health Comprehensive Sickle Cell Center Grant HL38632 awarded to SKB.
PY - 1998/3/12
Y1 - 1998/3/12
N2 - Hydroxyurea has been mixed with hemoglobin S and the reaction was studied using electronic absorption spectroscopy as a function of time and wavelength. The rate of conversion of oxyhemoglobin S to other species was determined and the nature of the reaction products was studied. We also report the formation of methemoglobin (and other reaction products) when deoxyhemoglobin S is combined with hydroxyurea. The probable increase in the formation of methemoglobin, and other potential reaction products such as nitric oxide-hemoglobin, in patients with sickle cell anemia who are taking hydroxyurea as a therapeutic drug is discussed in terms of the pathophysiology of the disease. It is proposed that methemoglobin and possibly nitric oxide-hemoglobin formation may partially explain beneficial effects observed in these patients before their levels of fetal hemoglobin have increased.
AB - Hydroxyurea has been mixed with hemoglobin S and the reaction was studied using electronic absorption spectroscopy as a function of time and wavelength. The rate of conversion of oxyhemoglobin S to other species was determined and the nature of the reaction products was studied. We also report the formation of methemoglobin (and other reaction products) when deoxyhemoglobin S is combined with hydroxyurea. The probable increase in the formation of methemoglobin, and other potential reaction products such as nitric oxide-hemoglobin, in patients with sickle cell anemia who are taking hydroxyurea as a therapeutic drug is discussed in terms of the pathophysiology of the disease. It is proposed that methemoglobin and possibly nitric oxide-hemoglobin formation may partially explain beneficial effects observed in these patients before their levels of fetal hemoglobin have increased.
KW - Hydroxyurea
KW - Methemoglobin
KW - Nitric oxide
KW - Sickle cell hemoglobin
KW - Time resolved absorption spectroscopy
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U2 - 10.1016/S0304-4165(97)00132-3
DO - 10.1016/S0304-4165(97)00132-3
M3 - Article
C2 - 9545536
AN - SCOPUS:0032510287
SN - 0304-4165
VL - 1380
SP - 64
EP - 74
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 1
ER -