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Iron metabolism : recent aspects of biochemical tools Volume 2, issue 1, Janvier - Février 1996

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Laboratoire central de biochimie, laboratoire associé de médecine nucléaire, Centre hospitalier universitaire Henri-Mondor, 94010 Créteil.

Parameters classically used to study iron metabolism include measures of sideremia and total iron binding capacity of transferrin. Other biological tools provide a precious help in the investigation of iron disorders. In this setting seric ferritin assays allow to specify the tissue iron content. More recently, the determination of ferritin levels in erythrocystes (these levels are closely related to the amount of iron available for erythropiesis) and soluble transferrin receptors assays have been available in current practice. Moreover, these two last tests are not yet been approved by the reglementory authorities and should be reserved in a second time of the investigation process. Ferritin assays in erythrocytes is especially used for the diagnosis and follow-up in iron overload patients. Soluble transferrin receptor assay is helpfull tool for the diagnosis of iron deficiency and notably when an acute phase syndrom is associated and lead to a difficult interpretation of ferritinemia results. Different proteins which have been recently identified such as mucins, integrins, mobiferrin… highlight the molecular mechanisms of iron absorption by enterocytes. Likewise, the discovery of an identical untranslated sequence in mRNA (IRE : iron responsive element) of both H and L chains of ferritin, in mRNA of delta-ALA synthase and in mRNA of TfR have led to a better understanding of the regulation pathways. A soluble cytoplasmic protein (IRF : iron regulatory factor) binds to IRE in case of cellular iron deprivation ; this binding inhibits delta-ALA synthase and ferritin synthesis as well as transferrin receptors mRNA degradation. TfR synthesis is then enhanced and iron uptake increased. On the contrary, growing iron level induces IRF conformational changes which produces a release of IRF from IRE ; as a consequence, delta-ALA synthase and ferritin are produced again, and cellular iron uptake is reduced. So, we may consider IRF as an intracellular sensor and regular of iron. Such proteins let us hope that we will be able to specify how iron enters the cell and how this mechanism is regulated according to cellular needs. Furthermore the identification of hemachromatosis gene and the protein encoded will help to explain how iron works in human cells.