Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis
- 20 December 2010
- journal article
- review article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 64 (4), 281-286
- https://doi.org/10.1136/jcp.2010.079046
Abstract
Iron functionsIron is an essential micronutrient, as it is required for satisfactory erythropoietic function, oxidative metabolism and cellular immune response.Iron physiologyAbsorption of dietary iron (1–2 mg/day) is tightly regulated and just balanced against iron loss because there are no active iron excretory mechanisms. Dietary iron is found in haem (10%) and non-haem (ionic, 90%) forms, and their absorption occurs at the apical surface of duodenal enterocytes via different mechanisms. Iron is exported by ferroportin 1 (the only putative iron exporter) across the basolateral membrane of the enterocyte into the circulation (absorbed iron), where it binds to transferrin and is transported to sites of use and storage. Transferrin-bound iron enters target cells—mainly erythroid cells, but also immune and hepatic cells—via receptor-mediated endocytosis. Senescent erythrocytes are phagocytosed by reticuloendothelial system macrophages, haem is metabolised by haem oxygenase, and the released iron is stored as ferritin. Iron will be later exported from macrophages to transferrin. This internal turnover of iron is essential to meet the requirements of erythropoiesis (20–30 mg/day). As transferrin becomes saturated in iron-overload states, excess iron is transported to the liver, the other main storage organ for iron, carrying the risk of free radical formation and tissue damage.Regulation of iron homoeostasisHepcidin, synthesised by hepatocytes in response to iron concentrations, inflammation, hypoxia and erythropoiesis, is the main iron-regulatory hormone. It binds ferroportin on enterocytes, macrophages and hepatocytes triggering its internalisation and lysosomal degradation. Inappropriate hepcidin secretion may lead to either iron deficiency or iron overload.Keywords
This publication has 52 references indexed in Scilit:
- An update on iron physiologyWorld Journal of Gastroenterology, 2009
- Molecular mechanisms of normal iron homeostasisHematology, 2009
- Forging a field: the golden age of iron biologyBlood, 2008
- Direct interorganellar transfer of iron from endosome to mitochondrionBlood, 2007
- The role of transporters in cellular heme and porphyrin homeostasisPharmacology & Therapeutics, 2007
- Understanding Heme TransportThe New England Journal of Medicine, 2005
- Orchestration of Iron HomeostasisThe New England Journal of Medicine, 2005
- Disorders of Iron MetabolismThe New England Journal of Medicine, 1999
- Reversal of Long-Standing Iron Deficiency Anaemia after Eradication ofHelicobacter pyloriInfectionScandinavian Journal of Gastroenterology, 1997
- Toxic DNA Damage by Hydrogen Peroxide Through the Fenton Reaction in Vivo and in VitroScience, 1988