1. The main cellular site of iron storage is the liver, specifically in hepatocytes. Iron bound to transferrin is taken up from the blood by hepatocytes due to the binding of transferrin to the transferrin receptor. Free iron (called non-transferrin–bound iron, NTBI) in the plasma can also be absorbed by hepatocytes via the action of DMT1. However, the ferric form predominates in the blood and must first be reduced by ferrireductases prior to DMT1 transport. Upon binding transferrin, the transferrin receptor is internalized via receptor-mediated endocytosis. The acidic environment of the endosome results in the release of ferric iron from transferrin. The ferric iron is reduced in the endosome to the ferrous form via the action of an endosomal ferrireductase, most likely 6-transmembrane epithelial antigen of prostate protein 3 (STEAP3). The ferrous iron is transported out of the endosome via DMT1 action and can then be stored in the hepatocyte bound to ferritin as in intestinal enterocytes. The transferrin-transferrin receptor complexes are recycled back to the surface of the hepatocyte and the transferrin is released to the blood where it can bind more ferric iron in the circulation. Ferrous iron is released from hepatocytes to the circulation through the action of ferroportin. When in the circulation ferrous iron is oxidized to the ferric form by the plasma ferroxidase known as ceruloplasmin. The ferric iron can then be bound by transferrin and delivered to other tissues of the body. Reproduced with permission of the medical biochemistry page, LLC.
Source: Iron and Copper Metabolism, Integrative Medical Biochemistry Examination and Board Review
Citation: King MW. Integrative Medical Biochemistry Examination and Board Review; 2014 Available at: Accessed: December 19, 2017
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