Ligand Binding and Sickle Hemoglobin Polymerization Kinetics: Implication for Therapies
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چکیده
منابع مشابه
Ligand kinetics in hemoglobin Hiroshima.
Hemoglobin Hiroshima is an electrophoretically fast-moving variant with a fourfold increase in oxygen affinity and a decreased Bohr effect. Based on a decreased rate of dissociation of O(2) in the presence of dithionite and an increased rate of binding of CO by the deoxy form, we have concluded that the kinetic basis of the high affinity exhibited by Hb Hiroshima is the concurrence of a faster ...
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To determine the extent to which the broad distribution in intracellular hemoglobin concentrations found in sickle erythrocytes affects the extent of intracellular polymerization of hemoglobin S, we have fractionated these cells by density using discontinuous Stractan gradients. The amount of polymer formed in the subpopulations was experimentally measured as a function of oxygen saturation usi...
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correlated positively and negatively with the percentage of normal and abnormal cells, respectively (Figure 1B-C). Fluorescent labeling of HbF allowed us to discriminate nonF-cells (Figure 1Di-ii) fromF-cells (Figure 1Diii-iv), and analyze their shape as captured in the brightfield images. The images confirmed the prediction that some RBCs with detectable HbF content still sickle (Figure 1Div),...
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The rates of polymerization and depolymerization of identical concentrated deoxygenated hemoglobin S (HbS) solutions following a rapid temperature change were examined by several methods. Two of these methods measured viscosity changes in either gently agitated (AGT) or nonagitated (NAGT) samples. The third method utilized a change in turbidity at 735 nm (SDT). By all three methods, a delay per...
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In the last few years. the understanding of the molecular basis of sickle cell disease has progressed rapidly. It is now possible to describe the structure of the gel of polymerized deoxyhemoglobin S at molecular and atomic levels and to begin to understand the mechanism of formation of this gel from hemoglobin solutions. There are several current hypotheses for the pathophysiology of this dise...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2009
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2008.12.299