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2,3-Diphosphoglycerate and intracellular pH as interdependent determinants
of the physiologic solubility of deoxyhemoglobin S
WN Poillon and BC Kim
Center for Sickle Cell Disease, Howard University, Washington, DC 20059.
We have established that 2,3-diphosphoglycerate (2,3-DPG) content and
intracellular pH exert separate, but interdependent, effects on the
equilibrium solubility (csat) of deoxyhemoglobin S (deoxy-Hb S) that act in
concert to modulate intraerythrocytic polymer formation. In a
nonphysiologic csat assay system, a steep dependence of csat on pH in the
physiologic range 7.0 to 7.6 was shown for both stripped (Hb) and
DPG-saturated deoxy-Hb S (Hb-DPG). The solubility-pH profile for Hb under
near-physiologic buffer conditions also showed that csat increased steeply
in the same pH range (6.8 to 7.6). The effect of 2,3- DPG on csat under
near-physiologic conditions was evaluated separately. At pH 7.20, the pH of
the human red blood cell, csat values for Hb and Hb-DPG were 19.56 +/- 0.14
and 17.95 +/- 0.45 g/dL, respectively, indicating that the solubility of
Hb-DPG is lower than that of Hb by 8.2% +/- 2.3%. Thus, binding of 2,3-DPG
in the beta-cleft promotes the polymerization of deoxy-Hb S, the ultimate
determinant of cell sickling. Furthermore, because of the abnormal Bohr
effect of sickle blood (approximately double that of normal blood), the
intracellular pH of deoxygenated sickle erythrocytes should be
approximately 0.28 pH unit higher than that of oxygenated cells (ie, 7.41 v
7.13). At the higher pH, the corresponding csat for Hb-DPG is 20.22 g/dL,
which is the best estimate of the intrinsic solubility of T-state Hb S
under conditions that approximate closely those of pH, temperature, ionic
strength, and 2,3-DPG saturation in the fully desaturated sickle
erythrocyte.
Volume 76,
Issue 5,
pp. 1028-1036,
09/01/1990
Copyright © 1990 by The American Society of Hematology
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