Thermal (Or Endothermic) Aggregation of Sickle Cell Hemoglobin (Hb S) During Sickling
The human hemoglobin molecule consists of 4 polypeptide chains, one pair designated the α’s and the other the β’s. Sickle cell hemoglobin (Hb S) differs from the normal by a single amino acid substitution at the 6th position in each β chain. It further appears that there is a hydrophobic pocket in each of the a chains which is complementary to the β-6-Valyl region, allowing deoxygenated sickle cell hemoglobin (Hb S) tetramers to stack by hydrophobic interactions. When oxygenated, the β chains move closer to each other by about 5 angstroms and the stacking crumbles because the goodness of fit is lost, This is unsickling by conformational change. There is another unsickling mechanism which involves an entropy change. In 1957 I reported that Hb S has a negative temperature coefficient of aggregation, i.e., a deoxygenated Hb S solution at 0° gels when warmed to 38° C but liquefies reversibly when replaced in the ice bath. Thus, the sickling phenomenon involves a thermal (or endothermic) aggregation of Hb S. The energy of activation for this reaction (ΔH*) is 17.3 kCal mole-1 and the entropy change amounts to 55 e. u. It appears reasonable to assume that the same entropy change is required to set a molecule of water free from the hydration layer about the hydrophobic residues as is required in the melting of ice.
KeywordsEntropy Change Tobacco Mosaic Virus Hydration Layer Negative Temperature Coefficient Thermal Aggregation
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