TY - JOUR T1 - Intracellular polymerization of sickle hemoglobin. Effects of cell heterogeneity. AU - Noguchi,C T, AU - Torchia,D A, AU - Schechter,A N, PY - 1983/9/1/pubmed PY - 1983/9/1/medline PY - 1983/9/1/entrez SP - 846 EP - 52 JF - The Journal of clinical investigation JO - J Clin Invest VL - 72 IS - 3 N2 - 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 using 13C nuclear magnetic resonance spectroscopy. The results for each subpopulation are in very good agreement with the theoretical predictions based on the current thermodynamic description for hemoglobin S gelation. We further demonstrate that the erythrocyte density profile for a single individual with sickle cell anemia can be used with the theory to predict the amount of polymer in unfractionated cells. We find that heterogeneity in intracellular hemoglobin concentration causes the critical oxygen saturation for formation of polymer to shift from 84 to greater than 90%; polymer is formed predominantly in the dense cells at the very high oxygen saturation values. The existence of polymer at arterial oxygen saturation values has significance for understanding the pathophysiology of sickle cell anemia. The utility of these techniques for assessing various therapeutic strategies is discussed. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/6886006/Intracellular_polymerization_of_sickle_hemoglobin__Effects_of_cell_heterogeneity_ L2 - https://doi.org/10.1172/JCI111055 DB - PRIME DP - Unbound Medicine ER -