Physiological intestinal iron transport system

The physiological intestinal iron transport system is a multi-protein pathway responsible for the absorption of dietary iron and its regulated release into the systemic circulation [NIH, 2021]. It primarily functions in the proximal duodenum, where ferric iron (Fe3+) is reduced by duodenal cytochrome B (DCYTB) and transported into enterocytes by divalent metal transporter 1 (DMT1) [PubMed, 2014]. Within the cell, iron is either stored in ferritin or exported across the basolateral membrane by ferroportin (FPN1), a process requiring the ferroxidase hephaestin to enable binding to plasma transferrin [NIH, 2014]. The entire system is under the tight control of hepcidin, a liver-derived hormone that regulates iron levels by inducing the internalization and degradation of ferroportin [NIH, 2011]. Dysregulation of this system is central to various hematological and metabolic disorders, such as iron deficiency anemia and hereditary hemochromatosis [NIH, 2021]. Pharmacological interventions include iron replacement therapies, hepcidin mimetics (e.g., rusfertide), and ferroportin inhibitors (e.g., vamifeport), which aim to restore iron balance and prevent the toxic effects of iron overload or the systemic consequences of deficiency [PubMed, 2011].

Other names

Intestinal iron absorption pathwayDuodenal iron transport systemEnterocyte iron transport systemIntestinal iron homeostasis system

The system is modulated through substrate supplementation with oral or intravenous iron, pharmacological inhibition of the basolateral iron exporter ferroportin, mimicry of the regulatory hormone hepcidin to induce ferroportin degradation, or transcriptional regulation of transporters via HIF-2α inhibition [NIH, PubMed].