Relation between structure, co-operativity and spectra in a model of hemoglobin action

Abstract

A quantitative understanding of co-operativity in hemoglobin must include a description of where and how the free energy of co-operation is stored in the molecule. Experiments to date have not succeeded in associating this energy with a particular bond. One extreme possibility is that the free energy is stored as small amounts of strain energy in many bonds, so that all bonds are almost normal. A linear distributed energy model can be constructed when the strain energies of bonds are sufficiently small. This model relates quantitatively small structural changes at the heme group, upon ligation, to the free energy of cooperation, although the energy of co-operation is not chiefly stored at the heme group in this model. It is in accord with the non-co-operativity of the oxidation of hemoglobin 2+ → aquo-methemoglobin 3+ at pH 6, and describes the magnitude of changes observed in the Soret band when the quaternary structure is changed. It accounts for the scale of the motions in the heme region due to changes in the quaternary structure, and provides a framework for discussion of spectral and structural changes for affinity affectors which are not located near the heme group. The general model should be of use for discussing other cases of the control of local chemical properties by proteins.