Hepcidins

Hepcidins are a family of small cysteine-rich peptides produced by the liver in humans and other animals. They play a crucial role in regulating iron metabolism in the body. Hepcidin is synthesized as a preprohormone and undergoes two cleavage steps before being secreted into the bloodstream, where it can bind to iron-binding proteins such as transferrin.

Hepcidin acts as a key regulator of dietary iron absorption, recycling, and storage, and iron exported from cells. It inhibits iron release from enterocytes, macrophages, and hepatocytes by binding to ferroportin, the only known iron exporter. In addition, hepcidin regulates iron absorption from the gut by reducing the expression of divalent metal transporter 1 (DMT1), which is necessary for iron uptake.

There are two main forms of hepcidin, hepcidin-25 and hepcidin-20. Hepcidin-25 is the most abundant form and has the longest half-life. Hepcidin levels increase in response to elevated iron stores, inflammation, or oxidative stress, and decrease in response to iron deficiency or anemia. Hepcidin is also involved in the development of anemia of chronic disease (ACD), a condition characterized by impaired erythropoiesis and iron deficiency in the setting of chronic inflammation.

Mutations in the HAMP gene encoding hepcidin have been implicated in familial hypoferritinemia, a rare disorder characterized by low serum iron and very low transferrin saturation, despite normal iron intake. Understanding the role of hepcidins in iron metabolism has shed light on the pathogenesis of various iron-related disorders, including ACD, iron overload, and genetic disorders affecting hepcidin levels or function.