UPTAKE OF IRON FROM N-TERMINAL HALF-TRANSFERRIN BY ISOLATED RAT HEPATOCYTES - EVIDENCE OF TRANSFERRIN-RECEPTOR-INDEPENDENT IRON UPTAKE

The aim of the present study was to determine if human N-terminal half -transferrin (N-fragment), prepared by thermolysin cleavage of diferri c transferrin, would bind to the rat hepatocyte transferrin receptor a nd donate iron to the cell. Competition experiments between I-125-labe lled N-fragment and diferric transferrin revealed no receptor binding of the half-transferrin. Still, the N-fragment delivered iron to the c ells in amounts approximately 30-fold above what could be accounted fo r by uptake of the fragment itself. The rate of celluar iron uptake fr om the fragment was comparable to what is seen with the intact transfe rrin. The uptake of I-125-labelled N-fragment was not inhibited by exc ess non-radioactive diferric transferrin. By comparison, the uptake of Fe-59 from the N-fragment was inhibited 70% by excess nonradioactive diferric transferrin. This suggests that iron derived from diferric tr ansferrin competes with the iron derived from the N-fragment for a com mon transport pathway. Although some cellular degradation of the N-fra gment occurred, the extent of degradation was too low to explain the a mount of iron accumulated by the cells. The results show that the hepa tocyte has an effective transferrin-receptor-independent mechanism for accumulation of iron from transferrin.