title: Erythroblast iron metabolism in sideroblastic and sideropenic states.
abstract: Iron appears to exert self-regulatory control over erythroblast iron uptake, iron storage and its incorporation into haem. It does this via iron regulatory proteins (IRPs) which bind reversibly to the iron responsive elements (IREs) on the mRNA of transferrin receptor (TfR), erythroid 5-aminolaevulinic acid synthase (ALA-S2) and ferritin. Iron deficiency leads to the binding of IRP to IRE. This binding inhibits the translation of mRNA for ALA-S2 and ferritin but stabilizes mRNA for TfR expression. Sideroblastic erythropoiesis is highly ineffective and characterized by mitochondrial iron loading. The study of X-linked sideroblastic anaemia has shown that the entry of iron into the mitochondria is poorly controlled and able to occur when protoporphyrin production is reduced, as is seen with the ALA-S2 mutations, or when it is increased as has been seen with ABC7 transporter mutations. Sideropenia characterises both iron deficiency anaemia (IDA) and the anaemia of chronic disease (ACD). Erythroblasts in ACD seem doubly equipped to protect their iron supply with their ability to increase the efficiency of transferrin-iron uptake as well as to activate the IRP/IRE system to increase surface TfR production. This increase in efficiency restricts the need to increase surface TfR production and maintains serum soluble TfR (sTfR) values within the normal range in iron replete ACD. The coexistence of iron deficiency with chronic disease, however, is associated with an increase in both the efficiency and number and a highly significant rise in sTfR values.
authors.affiliation: University Department of Haematology, The Western Infirmary, Glasgow, UK.
authors.forename: Lorna A
authors.initials: LA
authors.lastname: McLintock
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fitzsimons
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood*; D000756:Anemia, Sideroblastic / Q000097:blood*; D001692:Biological Transport; D004900:Erythroblasts / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*
chemical_list: D007501:Iron