An allosteric model of hemoglobin: I, kinetics

Abstract

The allosteric model of Monod, Wyman & Changeux (1965; the Monod model) has been used to analyze the kinetics of ligand binding to mammalian hemoglobins. Combination velocity constants and dissociation velocity constants for the T and R forms were evaluated from the early measurements by Roughton & Gibson of the oxygen and carbon monoxide binding to sheep hemoglobin at pH 9.1 and more recent measurements of oxygen binding to human hemoglobin at pH 7. The difference in ligand affinities between the T and R forms, which is a factor of several hundred, is taken up almost equally by the combination and dissociation rates. The allosteric model is shown to be particularly suitable for explaining the flash photodissociation of carboxyhemoglobin. The monotonic decrease of the fraction of quickly reacting form with increasing flash intensity shown by Antonini, Chiancone & Brunori (1967) and the flow-flash experiments of Gibson & Parkhurst (1968) are both in excellent agreement with the calculations on the Monod model, with no adjustable parameters except for the fit to the equilibrium curves. In flow experiments, both the forward progess curves and the reverse dissociation curves after mixing with dithionite are very well described by the Monod model. Finally, Gibson's recent flow experiments on human hemoglobin at pH 7 have been shown to be consistent with the parameters of the Monod model which can describe the other kinetic experiments. From all this, we conclude that the kinetic experiments discussed can be fitted by the simple Monod allosteric model to well within the range of experimental errors, and that the kinetic data now available are not inconsistent with this model.