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Iron is a component of all living organisms. It plays an important metabolic role, particularly in electron transfer reactions. Much of the iron in the human body is in circulating red cells, which contain 1 mg of iron per 1 mL of packed cells. Iron is stored in the form of ferritin or hemosiderin. Smaller amounts of iron are present in myoglobin and in many enzymes. Because little iron is lost from the body under normal circumstances, the iron content of the body is regulated by modulating iron absorption. Separate pathways exist for the absorption of heme and inorganic iron. The process appears to involve a ferrireductase, a divalent iron transporter DMT-1, hephaestin, and ferroportin. Iron absorption increases in the presence of iron deficiency and it decreases when there is iron overload. The central regulator or iron homeostasis is the hepatic antimicrobial peptide hepcidin. Ferroportin serves as the receptor for hepcidin and is destroyed when the complex is formed. This impairs transport from intestinal mucosal cells and from macrophages into the plasma, and serves to lower iron absorption and plasma iron levels and to increase macrophage iron. Once ferric iron enters the plasma, it is bound by transferrin, which after forming a complex with the transferrin receptor, transports the metal into cells. The transferrin receptor is internalized together with bound transferrin and iron, and the iron is released inside the cell into an acidified vacuole. The transferrin receptor then recycles to the cell surface.

Many of the proteins involved in iron homeostasis are regulated by the abundance of iron through binding of one of the iron-regulatory proteins (IRPs) to iron-responsive elements (IREs) located within stem loop structures of the corresponding messenger ribonucleic acids (mRNAs). IRP-1 is cytoplasmic aconitase that binds to the IRE when it is not complexed with iron and does not bind when iron is present; IRP-2, a closely related protein, is destabilized by the presence of iron. When IRPs bind to IREs at the 5′ end of the mRNA, they prevent translation; when they bind at the 3′ end, they stabilize the message.

Iron deficiency and iron-deficiency anemia are common nutritional and hematologic disorders. In infants and young children iron deficiency is most commonly caused by insufficient dietary iron. Rarely, it can result from mutations in TMPRSS6, a gene encoding a membrane protease that serves normally as a downregulator of hepcidin transcription. In young women, iron deficiency is most often the result of blood loss in menstruation or as a result of loss during pregnancy and childbirth. In older adults, bleeding may be from the gastrointestinal tract, as from hemorrhoids, peptic ulcer, hiatus hernia, colon cancer, or angiodysplasia. It may result from uterine leiomyomas or carcinoma, or a renal tumor. Pulmonary blood loss may be etiologic through chronic hemoptysis caused by infection or malignancy, or as a result of idiopathic pulmonary hemosiderosis. However, bloody sputum may be swallowed, and pulmonary bleeding may be mistaken for gastrointestinal bleeding. ...

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