Iron release from transferrin: synergistic interaction between adenosine triphosphate and an ammonium sulfate fraction of hemolysate.

In previous work we have shown that red cell hemolysates, at neutral pH, will release iron from transferrin; with molecular sieve chromatography, that activity separated into low molecular weight and high molecular weight components, both susceptible to destruction by phosphatases. Thus the possibility that nucleotides might be involved was suggested. We have studied the interaction of adenosine triphosphate (ATP) and an ammonium sulfate fraction of hemolysate with transferrin. ATP, as well as adenosine diphosphate and 2,3-diphosphoglyceric acid, interacts synergistically with the ammonium sulfate hemolysate fraction to promote iron release from transferrin. This activity is not limited to phosphorylated compounds, because citrate shows a similar effect. This activity is not a nonspecific chelating effect, because deferoxamine is without activity. All the synergistic anions labilize transferrin's HCO3. We therefore suggest that they form a non-HCO3 ternary complex with transferrin and iron, and that release of iron from this complex is promoted by a high molecular weight constituent of the hemolysate.