Systemic iron-dependent metabolic pathways

Systemic iron-dependent metabolic pathways encompass the complex, highly regulated network of processes that manage iron absorption, transport, recycling, and storage to maintain homeostasis (Ganz, 2013). Iron is an essential cofactor for numerous proteins involved in oxygen transport, DNA synthesis, and energy metabolism, but its redox activity can also generate damaging reactive oxygen species (Abbaspour et al., 2014). The central regulator of this system is the hepatic hormone hepcidin, which controls the systemic availability of iron by binding to and inducing the internalization of ferroportin, the only known cellular iron exporter (Nemeth & Ganz, 2021). Dysregulation of these pathways leads to significant morbidity, ranging from iron deficiency anemia to iron overload conditions like hereditary hemochromatosis and transfusion-dependent thalassemias (Camaschella et al., 2020). Pharmacological management involves a variety of strategies, including the use of iron chelators to mitigate overload, iron supplements to treat deficiency, and novel therapeutics like hepcidin mimetics or ferroportin inhibitors that target the hepcidin-ferroportin axis (Knutson, 2017). These pathways are critical therapeutic targets because maintaining the delicate balance of iron is vital for both preventing tissue toxicity and ensuring adequate supply for erythropoiesis and cellular function.

Other names

Iron homeostasisSystemic iron metabolismHepcidin-ferroportin axisIron regulatory network

Drugs targeting systemic iron pathways function through several distinct mechanisms: 1) Iron supplementation to replenish stores in deficiency; 2) Iron chelation to bind and excrete excess iron; 3) Hepcidin mimetics to reduce iron export into plasma; 4) Ferroportin inhibitors to block iron release from cells; and 5) Erythropoiesis-stimulating agents that increase iron utilization for red blood cell production.