Hepatic uptake of iron by receptor-mediated and receptor-independent mechanisms

Hepatocytes can accumulate iron from transferrin via receptor- or non-receptor-mediated endocytosis or from non-transferrin iron complexes. The latter is several times more efficient than the transferrin-mediated uptake. Both pathways have some properties in common and mutually influence each other: Whereas on the one hand the non-permeant chelator DTPA as well as a polymer-conjugated desferrioxamine inhibit uptake of iron from transferrin, transferrin (in both forms, diferric or apo) itself inhibits uptake from the Fe(3+)-DTPA complex. At neutral pH, strong stimulation by reductant is observed, as well as inhibition by the prototropic agent chloroquine. This situation is reversed at acidic pH. Weak chelators stimulate uptake of iron from Fe-DTPA in hepatocytes. We conclude that the cell can labilize the chelate complex. The further mechanism of membrane passage is dependent on the environment. All the acquired iron can be found in ferritin.