Ionic strength dependence of the polymer solubilities of deoxyhemoglobin S + C and S + A mixtures.
Factors contributing to the clinical differences between sickle cell-hemoglobin C disease (SC) and the benign sickle cell trait (AS) include the higher proportion of hemoglobin (Hb) S and the higher cell Hb concentrations in SC compared with AS red cells. Reports differ, however, about whether Hb C copolymerizes more than Hb A with Hb S when measured by minimum gelling concentrations (MGCs) and polymer solubilities of the deoxy-Hb mixtures. We now show that the MGCs and solubilities of equimolar mixtures of Hb S + Hb C vary much more with the ionic strength (mu) of the solution than those of Hb S + Hb A mixtures. At mu less than or equal to 0.20, but not at mu greater than 0.25, Hb S + Hb C solubilities were significantly lower than those of Hb S + Hb A. These differences which may reflect a greater effect of the beta 6Lys+ in Hb C at lower mu, can account for the reported discrepancies. The solubility differences were similar in the presence or absence of asymmetric hybrids, and since the intratetramerically cross-linked hybrids alpha 2 beta s beta A and alpha 2 beta s beta c had similar solubilities, they did not indicate the usual mechanism, involving greater incorporation of alpha 2 beta s beta c into the polymers. The small solubility differences between the two Hb mixtures at physiologic (red cell) concentrations of Hb and 2,3-diphosphoglycerate probably play a minor role in the clinical differences between SC and AS states.
D019794:2,3-Diphosphoglycerate; D003432:Cross-Linking Reagents; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D005782:Gels; D006441:Hemoglobin A / Q000378:metabolism*; D006443:Hemoglobin A2 / Q000378:metabolism*; D006444:Hemoglobin C / Q000378:metabolism*; D006450:Hemoglobin SC Disease / Q000097:blood; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D009994:Osmolar Concentration; D012995:Solubility
D003432:Cross-Linking Reagents; D004163:Diphosphoglyceric Acids; D005782:Gels; D006451:Hemoglobin, Sickle; D046911:Macromolecular Substances; C038875:deoxyhemoglobin, sickle; D019794:2,3-Diphosphoglycerate; D006444:Hemoglobin C; D006441:Hemoglobin A; D006443:Hemoglobin A2