Binding of hepcidin to the only iron export protein
ferroportin (FPN) controls iron efflux in the cell13 causing its internalisation and lysosomal degradation of duodenal enterocytes and macrophages.1,14 This binding requires five N-terminal amino acids on hepcidin molecule, and absence of these amino acids makes another naturally occurring hepcidin-20, which is biologically inactive.2,9 In this way, by negative feedback mechanism, both iron absorption in the intestine and iron release from macrophages into plasma are controlled by circulating hepcidin.1
Recent studies have revealed that this peptide adjusts the immune performance with neutralizing
ferroportin in macrophages, hepatocytes, and enterocytes.
(4) The [Fe.sup.2+] is further exported to the abluminal side by
ferroportin. The exported [Fe.sup.2+] is oxidized to [Fe.sup.3+] by the astrocytic ferroxidase, glycosylphosphatidylinositol (GPI)-anchored cerulopasmin.
Heme oxygenase, transferrin receptor, and
ferroportin, consequently, made it plays a pivotal role in maintaining the body iron balance (20).
Iron and copper are exported from enterocyte by
ferroportin and ATP7A, respectively.
Oates, The role of hepcidin and
ferroportin in iron absorption, Histol Histopathol, 2007.
Chao et al., "Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues
Ferroportin and Ferritin Expression in Obese Mice," Journal of Nutrition and Metabolism, vol.
di Patti et al., "Ferroxidase activity is required for the stability of cell surface
ferroportin in cells expressing GPI-ceruloplasmin," The EMBO Journal, vol.
High intracellular iron levels in M1-like activated macrophages stabilize HIF1[alpha] through low levels of
ferroportin and high levels of H-ferritin, involved in iron export and storage, respectively [54, 55].
Hepcidin (peptide hormone) acts as negative regulator for iron release from cells [32] by binding to
ferroportin producing its internalization and degradation [33].
Two iron transport proteins, divalent metal transporter 1 (DMT1) and
ferroportin 1 (FPN), are expressed in duodenal enterocytes [4, 5].
Recently mutations of other genes encoding iron regulatory proteins, such as hepcidin, hemojuvelin, transferrin receptor 2, and
ferroportin, have been implicated in inherited iron overload syndromes [2].
