The linkage between oxygenation and subunit dissociation in human hemoglobin.

The use of subunit dissociation as a means of probing intersubunit contact energy changes which accompany cooperative ligand binding has been studied for the case of human hemoglobin. An analysis is presented delineating the information that can be obtained from the linkage relationships between ligand binding and subunit dissociation of hemoglobin tetramers into dimers. The analysis defines (a) the variation of the saturation function, Y, with total protein concentration, (b) the variation of the subunit dissociation constant (x)K(2) with ligand concentration (X) and (c) the correlations between changes in dimer-dimer contact energy and the sequential ligand binding steps. Sensitivity of the linkage function has been explored by numerical simulation. It is shown that subunit dissociation may appreciably affect oxygenation curves under usual conditions of measurement and that relying solely on either (x)K(2) or Y may lead to incorrect picutres of the energetics, whereas the combination defines the system much more exactly.