Physiological iron transport and storage pathways

Physiological iron transport and storage pathways encompass the complex systemic and cellular processes that maintain iron homeostasis, which is essential for oxygen transport, DNA synthesis, and cellular respiration [2, 8]. Key molecular players include transferrin, which transports iron in the blood, and the transferrin receptor, which facilitates cellular uptake via endocytosis [11, 14]. Intracellularly, iron is stored within the protein ferritin to prevent the formation of toxic reactive oxygen species through Fenton chemistry [6, 10]. The export of iron into the circulation is mediated by ferroportin, the only known cellular iron exporter, which is found on enterocytes, macrophages, and hepatocytes [2, 11]. Systemic regulation is primarily governed by the liver-derived hormone hepcidin, which binds to ferroportin and triggers its degradation, effectively reducing iron absorption and recycling [12, 15]. Clinical disorders arise when these pathways are disrupted, leading to conditions such as iron deficiency anemia or iron overload syndromes like hereditary hemochromatosis [8, 15]. Therapeutic interventions include iron salts or intravenous iron for deficiency, and iron chelators like deferoxamine for overload [1, 15]. Modern drug development also focuses on the hepcidin-ferroportin axis, with hepcidin mimetics and antagonists being investigated for treating anemias of chronic disease and iron-loading anemias [2, 15].

Other names

Iron metabolismIron homeostasisSystemic iron regulationIron transport and storage system

Drugs targeting these pathways work by supplementing iron levels in deficiency, chelating excess iron to prevent oxidative damage in overload, or modulating the hepcidin-ferroportin axis to regulate systemic iron distribution [2, 8, 15].