Translocation of different forms of transferrin from blood to bile in the rat

Five different forms of transferrin (rat apo [iron‐free], rat diferric, diferric rat asialo, human diferric, and diferric human asialotransferrin type 3) were used to monitor the passage of this protein and its metal to the bile. Cumulative biliary excretion of the dose over 3 hours was determined. In addition, an excretion profile was constructed from the concentration of tracer in bile samples collected over 10‐minute intervals. The profile obtained with apotransferrin was very similar to that found in an earlier study with albumin, the implication being that the apo form is transferred passively (e.g., by diffusion). Behavior of rat diferric transferrin, however, was consistent with the assumption that this form is transferred both passively and actively (i.e., in vesicles). The three other transferrins were investigated with the intent of broadening the spectrum of ligand affinities for the plasmalemma of hepatocyte. The higher this attraction was, the larger fraction of the dose appeared in bile. When transferrin was targeted to lysosomes, the bile contained several intermediate proteolytic fragments. Double‐labeled ( 125 I, 59 Fe) transferrin was used to measure recovery of iron (Fe) relative to the protein (P) in bile. With rat diferric transferrin, the Fe/P ratio was 0.72. Lower values were recorded with transferrins (human or asialo) that had higher affinities for the plasmalemma and therefore were expected to be transported to a larger extent in vesicles. Of the biliary 59 Fe, 85% to 92% was protein bound. The proportion of the protein‐bound fraction was essentially independent of the magnitude of Fe/P ratios. (H EPATOLOGY 1995; 21:1063–1069.)