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Iron Transport Proteins
Iron is distributed throughout the body by transport proteins specialized to both bind strongly to ferric iron during transport, and release their iron atoms where they are needed for physiological functions such as erythropoiesis.
Transferrin
Transferrin
Source: http://www.rcsb.org/pdb/molecules/pdb35_2.jsp
PDB ID: 1H76 Hall DR, Hadden JM, Leonard GA, Bailey S, Neu M, Winn M, Lindley PF, The crystal and molecular structures of diferric porcine and rabbit serum transferrins at resolutions of 2.15 and 2.60 A, respectively Acta Crystallogr D Biol Crystallogr. 2002 Jan;58 (Pt 1):70-80. Figure by David S. Goodsell The Scripps Research Institute.
Synthesized primarily by the liver, and then released into the plasma, transferrin is the body's primary plasma-borne iron transport protein. The role that transferrin plays in respect to iron is in many ways comparable to the role that hemoglobin plays toward oxygen. Both are recyclable, plasma-borne transport proteins that bind to and deliver an element essential to the functioning of virtually every cell in the body — an element that is nonetheless toxic in excess.
In states of rapid iron release and/or redistribution, high transferrin saturation levels can decrease the body's ability to bind to iron released from enterocytes (1). Hypotransferrinemia is a genetic disease in which insufficient transferrin production results in widespread toxicity from exposure to non-transferrin-bound iron (NTBI).
The transferrin molecule has two iron binding sites for ferric iron (Fe+3). Monoferric transferrin carries one iron atom; diferric carries two. When "empty," it is called apotransferrin. Although the rate of iron clearance from transferrin is rapid, the total capacity is limited.
Transferrin receptors
Transferrin receptors
Source: http://www.rcsb.org/pdb/molecules/pdb35_2.jsp
PDB ID: 1H76 Hall DR, Hadden JM, Leonard GA, Bailey S, Neu M, Winn M, Lindley PF, The crystal and molecular structures of diferric porcine and rabbit serum transferrins at resolutions of 2.15 and 2.60 A, respectively. Acta Crystallogr D Biol Crystallogr. 2002 Jan;58(Pt 1):70-80. Figure by David S. Goodsell The Scripps Research Institute.
Cells can control their iron uptake from circulating transferrin (top) by regulating the number of transferrin receptors (bottom) expressed on their surface, for example by iron response elements (IREs), which regulate mRNA transcription of transferrin receptors. Almost all cells have transferrin receptors, but they are found in greatest numbers on hepatocytes, immature erythrocytes, and both malignant and nonmalignant rapidly dividing cells (2,3).
Divalent metal transporter protein (DMT1)
In the duodenal enterocyte, DMT1 is responsible for transporting dietary non-heme iron (Fe2+) unidirectionally across the apical membrane into the cell (4). Divalent metal transporter protein is also involved in the transport of NTBI across cell membranes in both enterocytes and erythroid precursors.
Ferroportin (IREG)
Ferroportin is involved in the export of iron from inside cells. Like DMT1, ferroportin is specific for Fe2+ and functions unidirectionally. In enterocytes, ferroportin — with assistance from hephaestin — exports iron across the basolateral wall and into the plasma (5). The transport of iron may also be aided by the soluble plasma ferroxidase, ceruloplasmin, which performs a similar role as hephaestin. In hepatocytes, ferroportin upregulation can prevent cell damage by facilitating the excretion of excess iron (6). In senescent red blood cells and reticuloendothelial macrophages, ferroportin is directly involved in the export of iron during erythrocyte-iron recycling (7).