The Molecular Mechanism of Hemoglobin-facilitated Oxygen Diffusion

Abstract

Hemoglobin in solution augments the rate of steady state diffusion of oxygen. The flux of oxygen exceeds the diffusive flux by an amount, the facilitated flux, which is constant for a given hemoglobin concentration and is invariant with changing oxygen tension. The facilitated flux is inversely proportional to the length of the diffusion path. Facilitation decreases with increasing molecular size of the oxygen-binding proteins. From this it is concluded that facilitation results from random displacements of oxyhemoglobin molecules. Translational diffusion is considered to make a far larger contribution than rotatory diffusion. Facilitation is proportional to hemoglobin concentration in dilute solutions which approach ideal behavior and declines at greater protein concentration. It persists in very concentrated hemoglobin solutions (34%) in which the hemoglobin molecules are close packed. Facilitation requires no special property of hemoglobin other than reversible oxygen binding since hemerythrin which is not a heme protein facilitates oxygen diffusion. The reactions occurring during facilitated diffusion are shown to be combination and dissociation of hemoglobin and oxygen. Oxygen displacement or transfer reactions are excluded. The rates of chemical reactions may become rate-limiting. The rate-limiting step is a reaction of oxyhemoglobin. Comparison of the rates of facilitation by several hemoglobins suggests that the rate-limiting step is ligand dissociation. Facilitated carbon monoxide diffusion is minute compared to that of oxygen.