title: [Iron metabolism: State of the art].
abstract: About 60% of body iron is associated with hemoglobin in circulating red blood cells and daily erythropoiesis requires about 25 to 30mg iron per day. This iron is provided by macrophages through recycling of heme iron following phagocytosis of senescent red blood cells and heme catabolism. Intestinal iron absorption (1 to 2mg per day) only compensates for daily iron losses. Hepcidin, a 25 amino-acid peptide synthesized in hepatocytes, secreted in plasma and rapidly removed in urines, is a negative regulator of both intestinal iron absorption and heme iron recycling by macrophages. Hepcidin synthesis is stimulated by iron or by inflammation (mostly by IL-6) and is repressed by iron deficiency and by all conditions that stimulate bone marrow erythropoiesis such as anemia, bleeding, hemolysis, dyserythropoiesis or erythropoietin injections. A defect in the activation of hepcidin normally triggered by iron excess is the underlying mechanism for all juvenile or adult forms of hemochromatosis whereas a defect in hepcidin repression is responsible for an iron deficiency iron refractory anemia (IRIDA). Reduced hepcidin filtration in renal insufficiency contributes to the associated anemia and stimulation of hepcidin synthesis by inflammation is a major determinant of the anemia of chronic disorders. New therapeutic perspectives are currently underway such as the development of agonists or antagonists of hepcidin or siRNA approaches aiming at reducing hepcidin synthesis. The validation of hepcidin assays in a near future will allow identifying the patients most likely to benefit from intravenous iron therapy.
authors.affiliation: Inserm U773, université Paris Diderot, site Bichat, 16, rue Henri-Huchard, 75018 Paris, France. carole.beaumont@inserm.fr
authors.forename: C
authors.initials: C
authors.lastname: Beaumont
authors.forename: Z
authors.initials: Z
authors.lastname: Karim
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology; D006418:Heme / Q000378:metabolism; D006432:Hemochromatosis / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D051437:Renal Insufficiency / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D006418:Heme; D007501:Iron