Approaches to Cooperativity

Abstract

The central problem in the study of hemoglobin is to understand the mechanism of cooperativity, which manifests itself primarily in the sigmoidal saturation characteristic and the Bohr effect. At the outset we recognize that the matter cannot be simple because the iron atoms are separated by distances of 25 to 40 Å, which are much too great for direct (e.g. electromagnetic) interactions to be effective. In this chapter we discuss two general approaches toward the goal of understanding cooperativity in hemoglobin. The first one is thermodynamic in content and is based on a set of equilibrium equations constructed under a particular set of assumptions. In this category are the models proposed by Monod et al., (1965) and by Koshland et al., (1966). A rather different approach—one which seeks to understand cooperativity on the basis of the conformational differences between oxy- and deoxyhemoglobin—was employed by Perutz (1970, 1972).