Abstract
We have previously proposed a role of hydration in the allosteric control of hemoglobin based on the effect of varying concentrations of polyols and polyethers on the human hemoglobin oxygen affinity and on the solution water activity (Colombo, M. F., Rau, D. C., and Parsegian, V. A. (1992) Science 256, 655-659). Here, the original analyses are extended to test the possibility of concomitant solute and water allosteric binding and by introducing the bulk dielectric constant as a variable in our experiments. We present data which indicate that glycine and glucose influence HbA oxygen affinity to the same extent, despite the fact that glycine increases and glucose decreases the bulk dielectric constant of the solution. Furthermore, we derive an equation linking changes in oxygen affinity to changes in differential solute and water binding to test critically the possibility of neutral solute heterotropic binding. Applied to the data, these analyses support our original interpretation that neutral solutes act indirectly on the regulation of allosteric behavior of hemoglobin by varying the chemical potential of water in solution. This leads to a displacement of the equilibrium between Hb conformational states in proportion to their differential hydration.
Highlights
We present data which indicate that glycine and glucose influence HbA oxygen affinity to the same extent, despite the fact that glycine increases and glucose decreases the bulk dielectric constant of the solution
In our former studies of the effect of water activity on Hb O2 binding properties, we have used chemically different solutes like sucrose, stachyose, and polyethylene glycols to distinguish solute from water binding to Hb [1]
By using two different model approaches, the Wyman linkage equation or the Gibbs Duhem equation, we found that 65–721 water molecules are linked to the binding of four oxygen molecules to human Hb under the experimental conditions used
Summary
We present data which indicate that glycine and glucose influence HbA oxygen affinity to the same extent, despite the fact that glycine increases and glucose decreases the bulk dielectric constant of the solution. These analyses support our original interpretation that neutral solutes act indirectly on the regulation of allosteric behavior of hemoglobin by varying the chemical potential of water in solution. This leads to a displacement of the equilibrium between Hb conformational states in proportion to their differential hydration. Besides finding evidences for an indirect effect of solutes through water on the deoxy- to oxy-Hb conformational equilibrium, we have determined quantitatively this solvation effect on Hb allosteric transition in terms of the differential number of water molecules bound between the two extreme conformations of Hb. By using two different model approaches, the Wyman linkage equation or the Gibbs Duhem equation, we found that 65–721 water molecules are linked to the binding of four oxygen molecules to human Hb under the experimental conditions used. In contrast to our proposition, these results were interpreted by the same authors in terms of solute-specific differential binding to Hb, i.e. that sucrose acts as a weak allosteric effector or, alternatively, that the change in the oxygen affinity of Hb is due to the decreased dielectric constant of the water/sucrose solution as compared to pure water
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
