Transferrin, iron

Transferrin is essential for movement of iron and without it, as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary atransferrinemia is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy (10). 

Another potential source of iron, at least for hepatocytes, is receptor-independent uptake of iron from transferrin. This appears to involve an iron uptake pathway from transferrin which is neither suppressed in hepatocytes by antibodies to TfR (Trinder et at, 1988), nor by transfection of HuH-7 hepatoma cells with transferrin receptor anti-sense cDNA (Trinder etat, 1996). The same pathway may also be utilized for iron uptake from isolated transferrin N-lobe, which is not recognized by the receptor (Thorstensen et at, 1995). The possible role of TfR2 in this process remains to be established, as does the physiological importance of this pathway in intact liver. Human melanoma cells (Richardson and Baker, 1994) and Chinese hamster cells lacking transferrin receptors but transfected with melanotransferrin (Kennard et at, 1995) use another pathway for transferrin iron uptake, independent of the transferrin receptor, but utilizing iron transfer from transferrin or simple iron chelates to membrane-anchored melanotransferrin, and from there onwards into the cellular interior. 

Transferrin iron uptake via receptor-mediated endocytosis has clearly appeared fairly late in evolution, when we consider that the bilobal iron-binding protein is found only as far back as insects . As we have seen in the preceding chapters, iron-uptake mechanisms involving the synthesis of more or less specific siderophores have evolved together with strategies implying the solubilization of insoluble ferric iron by the combined effects of pH and reduction, and even the development of receptor proteins capable of taking up transferrin-, lactoferrin- or haem-bound iron from specific hosts. 

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 Iron transport into Trfr-/- mice (Levy et al, Impaired erythroid and... 

The aim of treatment of iron overload is to remove all potentially toxic iron from the body. In hereditary haemochromatosis this can be achieved by weekly phlebotomies of 500 ml until the desired serum ferritin concentration (mostly <50 gg/1) or a normal transferrin iron saturation is reached (Brissot et ah, 2000). 

In humans the clearance rate of Hb is higher than that of HpHb (L4, Lll). Murray et al. (M6) found this also to hold for rabbits and, by studying the elimination in nephrectomized animals, they also proved that the difference was not due to urinary loss of Hb. Analysis of the organs proved that the HpHb complex and Hb were assimilated mainly in the liver and were catabolized with an early reappearance of the iron as transferrin iron within 30 minutes. The free Hb accumulated also in the tubular cells of the kidneys. No data have been published suggesting that the spleen is of any appreciable importance in this respect. No typical exponential clearance of the HpHb complex from plasma was observed (L10, Lll) in the first few experiments. Lathem and Worley (L4) found that HpHb disappeared at a simple exponential rate in 5... 

The iron is transferred by the mucosal epithelium to the body and is bound to plasma transferrin in the ferric state. In the plasma, iron takes part in a dynamic transferrin-iron equilibrium and is distributed into vascular and interstitial extravascular compartment. 50 to 60% of transferrin is extravascular. The plasma iron pool in adults is about 3 mg and has an estimated turnover of 20 to 30 mg per 24 hours. Daily and obligatory losses of iron in healthy men are about 1 mg in healthy menstruating women these average 2 mg and in either case are compensated by a net absorption of 1 to 2 mg from the intestine, which enters the mobile pool of transferrin iron. 

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... 

MCV, mean cell volume MCHC, mean cell hemoglobin concentration SI, serum iron TIBC, transferrin iron-binding capacity. 

A system of internal iron exchange exists which is dominated by the iron required for hemoglobin synthesis. For formation of red blood cells, iron stores ean furnish It)—U> ingAl of iron, as compared to 1-1 mg from dietary sources Only ca 10 wl r+ of ingested iron actually is absorbed. Transferrin is essential for movement of iron and without it. as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary. iiransferrinemui is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy. 

Lactofenin, transferrin Iron-binding proteins with effects apparently similar to ETDA... 

Schade reviewed (114) the earlier studies on the role of serum transferrin in iron transport. Various early investigators had observed that the blood serum transferrin rapidly bound iron administered either through the gastrointestinal tract or by intravenous injection. There was a rapid turnover of iron in the blood serum and the degree of saturation of the transferrin was related to the amount of iron administered. In no instances, however, was the blood serum transferrin ever saturated with iron. Jandl et al. (71) have shown that both ovotransferrin and serum transferrin can transport plasma iron into red cells and that the transport is dependent on the concentration of transferrin. Iron taken up by the blood cells could not be eluted by subsequent incubation with iron-free transferrin solutions. More recently Morgan and Laurel (99) reported that iron uptake in reticulocytes is independent of the transferrin concentration. The iron complex of serum transferrin has a higher affinity for immature red cells than does the iron-free protein (72). Both bind specifically to immature red cells and the attachment permits the cells to remove the iron. Once the iron is removed, however, the iron-free transferrin can be replaced by an iron-transferrin complex. 

Fig. 21. Diagrammatic representation of known genetic variations of human transferrin. (Bearn, A. G. and W. C. Parker Some observations on transferrin. Iron Metabolism An International symposium, Aix-en Provence, France, 60 [1963]).

Keywords Aluminum, Iron, Transferrin, Iron regulatory protein, Alzheimer s disease... 

Roberts, S. Bomford, A. Chelation of transferrin iron by desferrioxamine in K562 cells. The partition of iron between ferrioxamine and ferritin. Biochem. J. 254 869-875 1988. 

Transport Ceruloplasmin (copper carrier), transferrin (iron carrier)... 

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