Free energy couplings between ligand binding and subunit association in hemoglobin are of first order.

The calculations presented in a recent paper [Johnson, M. L. (1986) Biochemistry 25, 791-797] to the effect that the free energy couplings between oxygen binding and subunit association in hemoglobin A can be of either first or second order are examined. The fitting of the experimental data to a system with second-order couplings carried out by Johnson belongs to a tetramer in which, in contradistinction to hemoglobin A, oxygen binding promotes subunit association.