Transferrin receptor expression in normal and iron overloaded liver.

Hepatocytes take up transferrin-bound iron by two mechanisms. One pathway consists in the binding of transferrin to high affinity receptor sites. This process results in receptor-mediated endocytosis and is highly efficient and saturable. The other mechanism involves low affinity, non-specific and non-saturable internalization of transferrin-bound iron, probably through pinocytosis, adsorptive endocytosis or low affinity binding sites. At low transferrin saturation, the first mechanism is quantitatively most important, at high transferrin saturation the latter mechanism becomes more significant. A mechanism whereby transferrin-bound iron is not endocytosed but reduced at and translocated through the plasma membrane has also been invoked and challenges the concept of (receptor-mediated) endocytosis of transferrin. However, this hypothesis remains to be confirmed.