Renal iron metabolism: transferrin iron delivery and the role of iron regulatory proteins.
نویسندگان
چکیده
I n mammalian cells, iron is required for the function of many prosthetic groups, including heme and iron-sulfur clusters. Mammals absorb dietary iron and heme across the apical mucosa of duodenal epithelial cells using a Fe transporter known as divalent metal transporter 1 (DMT-1; also known as solute carrier family 11 member 2, divalent cation transporter 1 (DCT1), and natural resistance associated macrophage protein 2) (1) or a specific heme transporter, heme carrier protein 1 (2). On the basolateral membrane, ferroportin (also known as mental transport protein 1 and iron regulated transporter 1) exports iron to the plasma (3), aided by hephaestin (4), which oxidizes ferrous (Fe ) to ferric (Fe ) iron. Serum transferrin (Tf), a 78-kD glycoprotein that is secreted mainly by the liver, binds one or two Fe atoms. Each Fe binds to four amino acid ligands from Tf and additionally binds a carbonate anion that stabilizes iron binding by providing two oxygen ligands. Carbonate binding completes occupancy of the six coordination positions of Fe and thereby stabilizes binding of Fe to Tf. Tf-bound iron circulates freely in the serum and extravascular spaces, and it serves as a source of iron for cells and tissues that are perfused by the systemic circulation, including liver, heart, muscle, kidney, and bone marrow (5). Excess intracellular iron is stored in ferritin, a heteropolymeric molecule that has a spherical shell structure and is composed of 24 H and L subunits, which can store up to 4500 iron atoms as a mineral core inside the shell (6). Iron can be released from ferritin when cells need more iron either when ferritin is degraded in the lysosome (7) or through a pore in the ferritin shell (8). Most cells modulate iron uptake by regulating the amount of Tf receptor 1 (TfR1) (9) that they express on the plasma membrane. The TfR functions as a dimer, and each 90-kD monomer has a single transmembrane-spanning domain. Upon binding iron-bearing Tf, the TfR-Tf complex is internalized into an early endosome, where acidification facilitates release of Fe from Tf and a reductase reduces Fe to Fe (10), which then can be exported into cytosol by DMT-1 in the late endosomal/lysosomal compartment. A second TfR that is expressed mainly by hepatocytes, TfR2, is not regulated by intracellular iron levels and is unlikely to be important in renal iron metabolism (11).
منابع مشابه
Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression.
Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher ...
متن کاملMicrocytic anemia, erythropoietic protoporphyria and neurodegeneration in mice with targeted deletion of iron regulatory protein 2 Running title: iron-limited erythropoiesis in mice with IRP2 deletion
متن کامل
RED CELLS Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2
Iron-regulatory proteins (IRPs) 1 and 2 posttranscriptionally regulate expression of transferrin receptor (TfR), ferritin, and other iron metabolism proteins. Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues. Despite this misregulation, there are no apparent pathologic consequences in tissues such as the liver and kidney. However...
متن کاملMicrocytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2.
Iron-regulatory proteins (IRPs) 1 and 2 posttranscriptionally regulate expression of transferrin receptor (TfR), ferritin, and other iron metabolism proteins. Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues. Despite this misregulation, there are no apparent pathologic consequences in tissues such as the liver and kidney. However...
متن کاملRelationship between serum levels of chromium and iron with transferrin and albumin levels as carrier proteins in diabetic patients with atherosclerosis
Backgrounds: Type 2 diabetes mellitus is one of the most common metabolic diseases in the world, resulting in complete or partial deficiency or resistance to insulin action. In this study, the association between serum levels of chromium and iron with serum levels of their carriers, transferrin and albumin in diabetic patients with atherosclerosis was investigated. Materials and methods: In ...
متن کاملThe effect of water borne nickel on iron metabolism and heme biosynthesis in common carp (Cyprinus carpio)
Nickel is an essential element for all living organisms such as microorganisms, plants and animals. When nickel concentration exceeds the necessary concentration, could be toxic, and likewise causes adverse effects in living organisms. In this study, following determining nickel LC50-96h for common carp (Cyprinus carpio), nickel sub-lethal treatments including 0 (control), 0.055, 0.275, 0.572, ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of the American Society of Nephrology : JASN
دوره 18 2 شماره
صفحات -
تاریخ انتشار 2007