[Regulation of the iron metabolism]

Abstract

Background: The regulation of iron absorption has previously been considered <<an enigma>>. Recent research has given us interesting information on the regulation of the iron metabolism and pathological iron overload; the present article aims at providing an overview of these topics.

Materials and methods: The article is based on a review of literature retrieved from PubMed.

Results: The peptide hepcidin binds to ferroportin on membranes of enterocytes, macrophages and hepatocytes. The complex is internalised and degraded and this results in decreased export of iron to the circulation, and thus a lower level of plasma iron. Hepcidin production is up-regulated in iron overload and down-regulated with iron deficiency. The liver proteins human haemochromatosis protein (HFE), transferrin receptor 2 (TfR2), haemojuvelin (HJV) and bone morphogenetic protein (BNP) are necessary regulators for activation of the hepcidin synthesis. Lack of or mutations in the genes for these proteins, e.g. the HFE mutation C282Y in primary haemochromatosis, reduces the synthesis of hepcidin. Iron regulatory proteins (IRP) may bind to iron responsive elements (IRE) of ferritin-mRNA and transferritin-mRNA and regulate the protein synthesis.

Interpretation: Regulation of uptake, utilization, release and storage of iron occurs at the gene level. Hepcidin is currently considered to be the <<key regulator>> of the iron balance. Intracellular iron balance is maintained by iron regulating proteins. Synthesis of ferritin increases with high iron levels, while synthesis of TfR1 is reduced. The opposite occurs with a low iron level.