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Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene. [5] Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell.
The misregulation of ferroportin in type 4 hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin. [8] Hemochromatosis type 4A is characterized by impaired iron export in cells.
Export occurs through ferroportin, often aided by hephaestin (Hp) and/or ceruloplasmin (Cp), and repressed by hepcidin. Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level.
Hephaestin, a ferroxidase that can oxidize Fe 2+ to Fe 3+ and is found mainly in the small intestine, helps ferroportin transfer iron across the basolateral end of the intestine cells. In contrast, ferroportin is post-translationally repressed by hepcidin, a 25-amino acid peptide hormone. The body regulates iron levels by regulating each of ...
In HEK 293 cells, Q248H was as predisposed to the activities of hepcidin-25 as wild type ferroportin. [27] Ferroportin Q248H also unregulated the expression of transferrin receptor-1 in the same way as wild type. This indicates the ferroportin Q248H is associated with mild clinical phenotype or causes iron disorder in the presence of other factors.
Hepcidin is a regulator of iron metabolism. It inhibits iron transport by binding to the iron export channel ferroportin which is located in the basolateral plasma membrane of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages), ultimately resulting in ferroportin breakdown in lysosomes.
The exceptions, people who have mutations in the gene for ferroportin, prove the rule: these people have plenty of hepcidin, but their cells lack the proper response to it. So, in people with ferroportin proteins that transport iron out of cells without responding to hepcidin's signals to stop, they have a deficiency in the action of hepcidin ...
Anemia of chronic disease (ACD) [1] [2] or anemia of chronic inflammation [3] is a form of anemia seen in chronic infection, chronic immune activation, and malignancy.These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver.