Systemic iron handling pathway

The systemic iron handling pathway is a coordinated physiological process that maintains iron levels within a narrow range to support essential functions like oxygen transport and DNA synthesis while preventing toxicity (Ganz, 2013, World J Gastroenterol). The pathway is primarily regulated by the liver-derived hormone hepcidin, which acts as a negative regulator by binding to ferroportin, the sole cellular iron exporter, leading to its internalization and degradation (Girelli et al., 2016, Blood). This mechanism controls iron absorption from the diet and iron release from storage sites like macrophages and hepatocytes (Ganz, 2013, World J Gastroenterol). Disruptions in this pathway can lead to iron deficiency, often manifesting as anemia, or iron overload disorders such as hereditary hemochromatosis, which can cause organ damage (Camaschella, 2015, N Engl J Med; Pietrangelo, 2010, Gastroenterology). Pharmacological targeting of this pathway includes the use of iron chelators to remove excess iron, hepcidin mimetics to reduce iron levels in polycythemia vera or hemochromatosis, and iron supplements or erythropoiesis-stimulating agents to treat deficiency (Crielaard et al., 2017, Br J Pharmacol). Key molecular components include transferrin for transport, ferritin for storage, and the transferrin receptor for cellular uptake (Camaschella, 2015, N Engl J Med). The pathway also involves sensing mechanisms like the HFE protein and hemojuvelin, which modulate hepcidin expression in response to iron status (Pietrangelo, 2010, Gastroenterology). Therapeutic strategies are increasingly focusing on the hepcidin-ferroportin axis to manage iron-restricted erythropoiesis in chronic inflammatory diseases (Girelli et al., 2016, Blood).

Other names

Iron homeostasisSystemic iron metabolismIron regulatory pathwayIron metabolism pathway

Modulation of iron levels through hepcidin agonism/antagonism, ferroportin inhibition, iron chelation, or direct iron supplementation (Crielaard et al., 2017, Br J Pharmacol).