A physiological model for hepatic metabolism of transferrin-bound iron

Hepatic iron and transferrin uptake following intravenous injection of purified native rat transferrin has been studied in the rat. Livers were removed at varying time intervals postinjection and were fractionated by isopycnic density gradient centrifugation. Neither 59Fe or 125I (labeling transferrin) appeared in the lysosomal or mitochrondrial fractions at any stage up to 14 days. 59Fe first appears in the supernatant zone of the sucrose gradient and with increasing time postinjection passes through regions of increasing density. By 16 h 59Fe became established at a density of 1.10 g/cm3 and it was identified as ferritin. Ferritin persisted labeled with 59Fe for up to 14 days. The study suggests hepatic iron uptake does not involve endocytosis. Iron is incorporated into ferritin of increasing density. This model can be used for the study of iron metabolism in human biopsy samples.