Disorders of iron metabolism I. Regulation of iron homeostasis


Authors: J. Novotný
Authors‘ workplace: Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc., Transfuzní oddělení a krevní banka FN Brno, pracoviště Bohunice, přednosta prim. MUDr. Eva Tesařová
Published in: Vnitř Lék 2005; 51(6): 681-689
Category: Original Contributions

Overview

Iron is an ubiquitously ocurring vital element which can be found in all living cell from bacterias and yeasts to mammals. The cells explore the redox potential of iron, which can be used in many essential and vital biochemical reactions. The iron homeostasis must be very finely tuned beacuse iron overload may lead to the generation of very toxic reactive oxid radicals, which may damage lipids, proteins and nucleic acids with possible severe cellular damage and death. Iron homeostasis is maintained on cellular and whole body levels and details of this fascinating network have been disclosed only very recently. The transferrin receptor (TfR) and ferritin play the main roles on cellular level of iron homeostasis maintaining. The expression of these proteins are under tight control of iron regulatory proteins (IRPs), which bind to specific parts of mRNA molecules, called iron regulatory elements (IREs). If the IRE is localized in 5’UTR (untranslated region) of mRNA molecule, the binding of IRP blocks translation of this mRNA. In case when the IRE lays in the 3’UTR, the binding of IRP stabilizes the mRNA and potentiates its translation. Excess of cellular iron causes high expression of ferritin genes and blocks the expression of TfR gene, in case of sideropenia the processes are reverse. The absorption and transport of iron to the blood by enterocytes and the retention or release of iron by macrophages represent the main regulatory processes of iron homeostasis on the whole body level. The enterocytes regulate the input of iron to the body by increasing or decreasing its absorption from the enteral lumen and its transport across the basolateral membrane to the blood. According to so called „preprogramming theory“ is the precursor cell of the enteral crypts preprogrammed by the body iron status to increased or decreased absorption and transport of iron. HFE protein, discovered by Feder et al. in 1996, plays very important role in these regulations. The C282Y mutation of HFE protein is the main cause of hereditary iron overload in causasoid populations worldwide as its homozygote status can be detected in more than 80 % of causasoid patients with hereditary hemochromatosis.

Key words:
iron – sideropenia – iron overload – hereditary hemochromatosis


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