Functional equivalence of the two iron-binding sites of human transferrin.

Abstract

FLETCHER and Huehns1,2 presented evidence that the two iron atoms bound to the serum iron-transport protein, transferrin are not equally available for the synthesis of haemoglobin by immature red blood cells (reticulocytes). They hypothesised that functional differences between the binding sites may serve to regulate the distribution of iron within the body3. Various studies (cited in ref. 4) have been published since, some of which support and some of which contradict this hypothesis. We devised procedures4 to compare the availability of iron at each site of transferrin for reticulocytes in vitro, as well as to compare the availability of iron in diferric and monoferric transferrin. In the homologous system of rabbit reticulocytes and rabbit transferrin, there was no functional difference between the two sites of diferric transferrin or between diferric and monoferric protein. In the heterologous system of rabbit reticulocytes and human transferrin, however, a difference between the sites of diferric transferrin and between diferric and monoferric transferrin was observed. Those studies have now been extended to the homologous system of human reticulocytes and human transferrin. We found no difference in availability of iron at the two sites of human transferrin and only a slight difference in the availability of iron in monoferric and diferric protein.