HEPCIDIN
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Figure hepcidin
Hepcidin is assumed to be
the master regulator
of iron homeostasis and is referred to as 'the iron regulatory hormone'.
Lack of or mutation in one of the genes encoding these proteins will result in unlimited release of iron from enterocytes or macrophages, which means that serum iron increases with subsequent iron overload in tissues (see primary haemochromatosis.
(HAMP is the gene that encodes hepcidin.)
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Interplay of key proteins in iron homeostasis
In the duodenal enterocyte, dietary iron is reduced to the ferrous state by duodenal ferric reductase (Dcytb), transported into and through the cell by divalent metal transporter (DMT1), reoxidised to the ferric state by hephaestin (ferrous oxidase) and by way of ferroportin released into the circulation.
Hepatocytes take up iron from the circulation either as free iron or transferrin-bound iron via transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2). TfR1 is widely found and responsible for iron uptake into cells. TfR2 may serve as a sensor of circulating transferrin-bound iron.
At present it is believed that 3 key proteins, HFE, TfR2 and hemojuvelin (HJV) in the liver, are necessary to activate a 4th protein, hepcidin. Hepcidin is secreted into circulation, where it down-regulates the ferroportin-mediated release of iron from enterocytes, macrophages, and hepatocytes. This results in reduced iron absorption and reduced release of iron to erythropoiesis, respectively. The production of hepcidin is down-regulated in iron deficiency and upregulated in iron overload.
(Please see a figure 3 of normal iron stores, low iron stores, and haemochromatosis from an article in Tidsskrift for Norsk legeforening Regulering av jernbalansen )
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Figure Normal iron homeostasis
The four hepatic proteins HFE, HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide) and TfR2 (transferrin receptor 2) are produced at normal levels. Hepcidin is produced according to iron status and regulates export of iron from enterocytes and macrophages.
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