In vitro and in vivo studies of iron delivery by human monoferric transferrins

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Abstract
Summary. According to the Fletcher‐Huehns hypothesis there exists a functional difference between the two iron‐binding sites of transferrin. In this study we present the results of an evaluation of this hypothesis in vitro and in vivo with human pure monoferric transferrins obtained by preparative isoelectric focusing in granulated gels. The uptake of iron from monoferric transferrins TfFec and FeNTf by erythroid bone marrow cells, hepatocytes and stimulated T‐lymphocytes in vitro was equal, even when both monoferric transferrins were present together in the incubation medium. Ferrokinetic studies in vivo, performed with both pure monoferric transferrins, showed that transferrin TfFec, as well as transferrin FeNTf, mainly deliver their iron to the erythron. As red cell 59Fe utilization, red cell iron turnover and other ferrokinetic parameters, obtained from this study, were identical too it is evident that both iron‐binding sites of transferrin are functionally homogeneous in vivo, with respect to iron delivery.