Intact heme groups undergo exchange between molecules of human hemoglobin under physiological conditions. This phenomenon requires the presence of ferrihemoglobin and is blocked by heme ligands or the prior binding of hemoglobin to haptoglobin. The kinetics of heme exchange between hemoglobins A and F allows a calculation of the rate constants for the dissociation of heme and globin. The rate of exchange of hemes between the non-α chains of ferrihemoglobins A and F is approximately 8 times that between the α chains. Mixtures of ferrihemoglobins and oxyhemoglobins exchange hemes at a rate greater than predicted from the rates of exchange observed in mixtures containing only oxyhemoglobin or ferrihemoglobin.

Ferriheme groups also undergo exchange between hemoglobin not bound to haptoglobin and methemalbumin, although at equilibrium the affinity of human albumin for ferriheme is only about one-fifteenth that of globin. Only primate albumins possess appreciable affinity for ferriheme; albumins from the nonprimate species examined appeared to be incapable of forming methemalbumin. Depletion of hemes from ferrihemoglobin by excess human albumin leads to the accumulation of free, precipitable globin.