Iron uptake in relation to transferrin degradation in the brain and other tissues of rats

The possibility that iron uptake by the brain involves transcytosis of the iron-transferrin complex across the brain capillaries, followed by degradation of the transferrin (Tf) within the brain, was investigated using diferric (I[Fe]Tf)-I-125-Fe-59 and [Fe-59]Tf coupled to I-125-tyramine cellobiose (TC). The radiolabeled catabolic products of proteins labeled with I-125-TC remain in the cells where degradation occurs. The TCTf complex behaved normally with respect to its ability to donate iron to rat reticulocytes in vitro or to the brain, liver, kidneys, and femurs in vivo. In the brain there was little difference in the uptake of I-125 derived from Tf and TCTf, and the amounts were equivalent to only a small fraction of the Fe-59 uptake. Hence, the rate of Tf catabolism in the brain was insufficient to account for the rate of accumulation of iron from plasma Tf. It was concluded that Tf recycles to the plasma after delivering its iron to the brain. The uptake of I-125 from TCTf by the liver and kidneys accounted for 40-50% of the total rate of Tf catabolism. This indicated that they were important but not the only sites of degradation of this protein.