Transferrin iron absorption/transport

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

Dosing for iron should be divided equally into two to three doses daily. An empty stomach (1 hour before or 2 hours after a meal) is preferred for maximal absorption. After absorption, iron binds to transferrin in the plasma and is transported to the muscles (for myoglobin), liver (for storage), or bone marrow (for red cell production). Iron is not actively excreted from the body but is lost through other measures already described.7 Some studies suggest that iron absorption may be... 

Transferrin Iron transport in plasma and into cells hpx mice (Huggenvik et al, 1989 Bernstein, 1987 Craven et al, 1987 Goya et al, 1972) Hypotransferinemia (Goya et al., 1972) microcytic anaemia increased iron absorption parenchymal iron overload... 

Transferrin receptor-2 Iron transport into hepatocytes Hereditary haemochromatosis (Camaschella et ah, 2000) increased iron absorption parenchymal iron overload... 

Absorption, transport, and storage of iron. Intestinal epithelial cells actively absorb inorganic iron and heme iron (H). Ferrous iron that is absorbed or released from absorbed heme iron in the intestine (1) is actively transported into the blood or complexed with apoferritin (AF) and stored as ferritin (F). In the blood, iron is transported by transferrin (Tf) to erythroid precursors in the bone marrow for synthesis of hemoglobin (Hgb) (2) or to hepatocytes for storage as ferritin (3). The transferrin-iron complexes bind to transferrin receptors (TfR) in erythroid precursors and hepatocytes and are internalized. After release of the iron, the TfR-Tf complex is recycled to the plasma membrane and Tf is released. Macrophages that phagocytize senescent erythrocytes (RBC) reclaim the iron from the RBC hemoglobin and either export it or store it as ferritin (4). Hepatocytes use several mechanisms to... 

Iron is best absorbed in the ferrous form or as heme. It is believed that transferrin, transported into the small intestine from the liver via bile, carries iron into the intestinal mucosal cells. Though about 16 mg of iron enter these cells every day, only 1-2 mg finds its way into the bloodstream. The rest remains bound to an iron storage protein called ferritin and is eventually lost in the feces in the normal sloughing-off process. Iron absorption also depends on its bioavail-... 

Serum transferrin has a more specialized fimction than simply iron sequestration, transporting iron from sonrces of iron in the body (e g. after absorption throngh the... 

The transmembrane transport of iron into eukaryotic cells was not well defined when these studies began. In fact, a eukaryotic iron transporter had not yet been identified. Even within the well-characterized manunalian transferrin-dependent iron transport system, the mechanism of transmembrane iron transport from the endosomal lumen into the cytosol was unknown [6]. It is important to characterize eukaryotic iron transport since disruption of iron homeostasis in humans results in disease. Anemia, due to iron deficiency is a serious health problem [7]. In addition, the common genetic disease hereditary hemochromatosis results, excess iron absorption from the gut which causes iron overload [8]. The excess iron accumulates... 

Figure 13-1 Free representation of some of the elements known to play a role in iron absorption, iron distribution and iron accumulation. The central circle indicates that in ways that are still not fully imderstood these various elements must be integrated into an overall protective function from tissue iron overload toxicity. GH, growth hormone CD8T, subpopulation of T lymphocytes CD8CD28, subpopulation of TCD8+ lymphocytes HFE, non-classical MHC class I gene C282Y and H63D, HFE mutations TfR, transferrin receptor pS61ck, kinase of importance in T cell activation, whose activity is diminished in CD8-I- cells in HH patients [36] DCTl, iron transporter gene.

Iron is normally absorbed in the duodenum and proximal jejunum. Normally. i-lO of dietary iron is absorbed (about OA-I mg day ) but this can be increased if iron. stores are low. Iron must be in the ferrous fomi for absorption, which occurs by active transport. In the plasma, iron is transported bound to transferrin, a P-globulin, There is no mechani.sm for the excretion of iron and the regulation of iron balance is achieved by appropriate chatiges in iron absorption. 

While several models of Cr(III) pharmacokinetics in mammals have been developed (111, 430, 502), little is known about Cr(III) speciation in organisms. Transferrin, a major transport protein for many metal ions (503), is likely to be the main Cr(III) carrier in blood (504). Although iron transport is a primary function of transferrin, the strength of its binding to Cr(HI) is comparable to that for Fe(III) (45, 505) and Cr -transferrin complexes [unlike for the complexes of Mn(II), Cu(n), or Zn(II)] mimic those of Fe(III) in interactions with cell transferrin receptors (506). Preliminary results of X-ray absorption spectroscopic studies suggest that Cr(lll) may occupy the same sites in the transferrin protein as Fe(lll) (507). 

Iron is an essential component of man s biochemistry but, in common with other elements, becomes toxic when in excess (3, ) This arises in part because of the tendency of iron(III) to separate in tissues as very insoluble hydroxide and phosphate salts at the physiological pH and higher unless bound to transferrin, the iron transport protein, or to ferritin, the iron storage protein. Iron absorption via the diet is physiologically controlled, but the body has no regulatory mechanisms for eliminating a toxic excess Introduced by accidental overdose or by multiple transfusions. 

Heme-iron, only present in animal foods, is more bioavailable compared to other sources contained in grains and vegetables. The consumption of animal products enhances iron absorption associated with grains. Another important enhancer of iron absorption is vitamin C because it chelates nonheme-iron under stomach acidic conditions, and keeps it soluble under the relatively neutral pH conditions of the duodenum. Vitamin C reduces ferric iron (Fe+ ) into ferrous iron (Fe+ ) in the stomach. The ferrous form is more efficiently absorbed by the duodenum epithelial cells. Heme-iron enters the epithelial cells complexed to porphyrin myoglobin and hemoglobin. The absorbed iron is stored in ferritin molecules located inside the intestinal cells and transported bound to transferrin. There are known inhibitors of iron absorption, the most important being phytates and fiber. 

Non-heme iron exists in plant products and its bioavailability is compromised by the concurrent ingestion of tannins, phytates, soy, and other plant constituents, that decrease its solubility in the intestinal lumen. Bioavailability of non-heme iron is increased by concurrent ingestion of ascorbic acid and meat products. Nonheme iron is reduced from the ferric to the ferrous form in the intestinal lumen and transported into enterocytes via the divalent metal transporter (DMT-1). Once inside the enterocyte, iron from heme and nonheme sources is similarly transported through the cell and across the basolateral membrane by the ferroportin transporter in conjunction with the ferroxidase hephaestin after which it can be taken up by transferrin into the circulation. The regulation of iron across the basolateral membrane of the enterocyte is considered the most important aspect of iron absorption. 

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