In vivo evidence for the functional heterogeneity of transferrin-bound iron. I. Studies in normal rats

Abstract

Functional heterogeneity of iron atoms bound to transferrin as postulated by Fletcher and Huehns was demonstrated by in vivo studies in rats. Serum transferrin was selectively double-labeled by adding 59Fe to 90 per cent saturation of iron binding capacity, incubation with rat reticulocytes to reduce the saturation to 50 per cent or less, and then adding back 55Fe. Rats were killed at various times after intravenous injection of this double-labeled transferrin, and the ratios of 55Fe to 59Fe were measured in plasma, circulating erythrocytes, bone marrow and spleen heme, whole liver and isolated hepatic Kupffer and parenchymal cells, and in small intestinal segments. Selective uptake of erythroblast-oriented 55Fe was observed in red cells and heme from marrow and spleen; storage-oriented 59Fe was selectively removed by liver cells and small intestine. Greater polarization was achieved by using Fe3+-nitrilotriacetic acid instead of ferrous ammonium sulfate and by injecting transferrin selectively double-labeled at less than 50 per cent saturation. These studies confirm the hypothesis of Fletcher and Huehns that the iron atoms of transferrin are functionally different and support the concept that transferrin plays a selective role in the distribution of iron to tissues in the rat.