Physiological non-heme iron uptake pathways

Physiological non-heme iron uptake pathways represent the complex network of proteins and processes responsible for the absorption of inorganic iron from the diet and its distribution to tissues. The primary site of absorption is the duodenum, where ferric iron (Fe3+) is reduced to ferrous iron (Fe2+) by the enzyme duodenal cytochrome B (DCYTB) and then transported across the apical membrane by divalent metal transporter 1 (DMT1) (McKie et al., 2001; Gunshin et al., 1997). Once inside the enterocyte, iron can be stored in ferritin or exported into the bloodstream via ferroportin, the only known mammalian iron exporter (Donovan et al., 2000). This export process is tightly regulated by the hepatic hormone hepcidin, which triggers the internalization and degradation of ferroportin to limit iron availability (Nemeth et al., 2004). In the circulation, iron is carried by transferrin and internalized by cells through transferrin receptor 1 (TfR1)-mediated endocytosis (Klausner et al., 1983). Dysregulation of these pathways leads to significant clinical conditions, such as iron deficiency anemia when uptake is insufficient, or hereditary hemochromatosis when uptake is excessive (Ganz, 2013). Therapeutic strategies targeting these pathways include iron supplementation, chelation therapy, and emerging hepcidin-targeted biologics.

Other names

Non-heme iron absorptionIntestinal iron transportCellular iron acquisitionDietary iron uptake

Provision of iron substrate for transport, chelation of excess iron, and modulation of the hepcidin-ferroportin axis to regulate iron export.