Figure 1.

Transport of dietary iron. Ferrous iron can enter the enterocyte cell in the form of haem. The exact method of haem uptake is yet to be elucidated, but Haem Carrier Protein 1 (HCP1) has been suggested to fill this role. Non-haem ferrous iron can enter the enterocyte cell in the form of ferritin via receptor mediated endocytosis, although a specific receptor is yet to be identified (Theil, 2004; Kalgaonkar and Lönnerdal, 2009). The main route of iron uptake in the duodenum is of “free” ferric iron, via a transferrin-independent mechanism. Iron is first reduced into a soluble form via a ferric reductase enzyme at the brush border of duodenal enterocytes. Transport into the enterocyte is then facilitated by the divalent metal transport 1 (DMT1). Once inside the enterocyte cell ferrous iron can be utilized for intracellular processes such as haem and Fe-S cluster biosynthesis, or stored in the molecule ferritin. Export primarily occurs, which is facilitated by ferroportin, at this stage iron is oxidized back to its ferric form by hephaestin. Most ferric iron passes through the fenestrated capillary endothelium of the intestine before being bound by the glycoprotein transferrin, where it is circulated within the plasma. Here transferrin bound iron can pass via transcytosis (Williams et al., 1984) across the capillary endothelium and into the interstitial fluid where it is delivered to tissues via transferrin receptor 1 (TfR1) mediated uptake (under normal physiological conditions). In cases of iron overload a pool of non-transferrin bound iron (NTBI) is formed, in which case iron uptake into most mammalian cells can also occur via NTBI uptake (Brissot et al., 2012).