Intestinal non-heme iron transport system

The intestinal non-heme iron transport system is a coordinated multi-protein pathway located in the duodenal enterocytes that mediates the absorption of inorganic dietary iron (Source: NIH). The process involves several key components: duodenal cytochrome B (DCYTB), which reduces luminal ferric iron (Fe3+) to ferrous iron (Fe2+); divalent metal transporter 1 (DMT1), which imports Fe2+ across the apical membrane; and ferroportin (FPN), the sole exporter that moves iron across the basolateral membrane into the blood (Source: PubMed). This export is facilitated by the ferroxidase hephaestin, which re-oxidizes iron for loading onto systemic transferrin (Source: NIH). The system is the primary regulator of body iron levels, as humans lack an active iron excretion mechanism (Source: PubMed). It is tightly controlled by the liver-derived hormone hepcidin, which binds to and triggers the degradation of ferroportin to inhibit iron entry into the circulation (Source: NIH). Pharmacological intervention in this system includes the use of oral iron salts to treat deficiency, hepcidin mimetics to manage iron overload, and chelators to prevent absorption (Source: NIH). Dysregulation of these transporters is central to the pathogenesis of iron deficiency anemia and hereditary hemochromatosis (Source: PubMed). Additionally, the system's activity is influenced by luminal pH and dietary factors like ascorbic acid, which enhances iron bioavailability (Source: NIH). Safety concerns with targeting this system include gastrointestinal side effects from oral iron and the risk of systemic iron overload.

Other names

Intestinal iron absorption pathwayDuodenal iron transport systemNon-heme iron uptake systemDMT1-Ferroportin axis

Substrate supplementation for DMT1-mediated uptake, hepcidin-mediated degradation of ferroportin, iron chelation to prevent absorption, and enhancement of ferric iron reduction by DCYTB.