Iron metabolism in the Belgrade rat.

Iron metabolism in the Belgrade rat was examined in the intact animal and in the reticulocyte suspensions. The plasma iron turnover was increased. However, when allowance was made for the effect of the elevated plasma iron concentration, erythroid marrow capacity for iron uptake was at basal levels. Numbers of erythroid cells in marrow and spleen measured by the radioiron dilution technique were increased. Thus iron uptake was not proportionate to the erythroid hyperplasia in the b/b rat, despite a more than adequate plasma iron supply. This relative deficiency in iron uptake was reflected in a severe microcytosis and elevated red cell protoporphyrin. Reticulocyte incubation studies demonstrated an unimpaired uptake of the transferrin-iron-receptor complex but a marked reduction in iron accumulation. The diferric transferrin molecule, when it did give up iron within the cell, released both of its iron atoms so that only apotransferrin was returned to the media. In contrast to the nearly complete release of iron within the normal reticulocyte, the major portion of iron taken up by the Belgrade reticulocyte was returned to the plasma. The release mechanism that can be impaired in iron-deficient reticulocytes by EDTA or cadmium was shown to be affected by lower concentrations of these substances in the Belgrade reticulocyte. It is concluded that the Belgrade rat has an abnormality of iron release within the absorptive vacuole that is responsible for a state of intracellular iron deficiency, involving the erythron and other body tissues.