Plasma iron transport

Figure 9.7 Iron transport by hepatocytes. Known proteins involved in iron transport across the plasma membrane of hapatocytes are represented. LMW = low molecular weight Trf = transferrin Trf-R = transferrin receptor HFE = hamochromatosis gene product 132m = 62-microglobulin 02-= superoxide OH- = hydroxyl radical FR = ferritin receptor SFT = stimulator of iron transport.

Figure 4.4 Comparison of oxidase-dependent iron transport in mammals and yeast. In mammals, the plasma glycoprotein cerulpolasmin mediates iron oxidation, facilitating iron export from the cells and delivery to other tissues throughout the body. In yeast, Fet3p, an integral membrane protein mediates iron oxidation, resulting in plasma membrane iron transport through the permease Ftrlp. Reprinted from Askwith and Kaplan, 1998. Copyright (1998), with permission from Elsevier Science.

The determination of the structure of the iron transporter, ferric-binding, protein (hFBP)t from Haemophilus influenzae (Bruns et ah, 1997) at 0.16 nm resolution shows that it is a member of the transferrin superfamily, which includes both the transferrins and a number of periplasmic binding proteins (PBP). The PBPs transport a wide variety of nutrients, including sugars, amino acids and ions, across the periplasm from the outer to the inner (plasma) membrane in bacteria (see Chapter 3). Iron binding by transferrins (see below) requires concomitant binding of a carbonate anion, which is located at the N-terminus of a helix. This corresponds to the site at which the anions are specifically bound in the bacterial periplasmic sulfate- and... 

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 8-9 Binds iron in plasma and transports iron to bone Iron deficiency, pregnancy, hypoxia, chronic blood loss, estrogens Chronic infection, cirrhosis, burns, enteropathies, nephrotic syndrome, cortisone, testosterone... 

Iron is transported via transferrin. When body stores of iron are high, ferric iron combines with apoferritin to form ferritin. Ferritin is the protein of iron storage. About 80 percent iron in plasma goes to erythroid marrow. The excretion of iron is minimal. Only little amount of iron is lost by exfoliation of intestinal mucosal cells and trace amount is excreted in urine, sweat and bile. 

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. 

Transferrin, which is the major iron-transport protein, holds two Fe(III) atoms per molecule, and it accounts for nearly all the iron in plasma, where its concentration is usually 2-5x 10-5 M [149]. In cells and tissues, the iron release from transferrin would be controlled by local pH variations in the presence of Fe(III) chelators [149]. Conflicting reports have been published on the ability of superoxide to initiate transferrin-promoted Fenton reactions [154]. 

Binds iron in plasma and transports iron to bone... 

Transferrin an iron-transport protein in the plasma, has a half-life of about 8 days thyroxine-binding protein, 2 days and retinol-binding protein, 0,4 days-Because of the relatively long half-life of albumin, the serum albumin level is not a particularly sensitive indicator of dietary protein status. Therefore, retinol-binding protein and thyroxine-binding protein have been used to assess malnutrition in poorly nourished populatiorrs. Note that these two proteins occur together as a complex in the bloodstream. 

There is some evidence that ceruloplasmin is involved in iron metabolism. It has been suggested that ceruloplasmin and ferritin in plasma work together to reduce the levels of free ferrous ions in plasma. Here, the ceruloplasmin catalyzes the oxidation of Fe (ferrous) to (ferric), the form of the metal that binds to ferritin. Ceruloplasmin acts as an oxidant in this process. This proposed function may reduce damage to membrane lipids possibly inflicted by the small amount of Fe in the circulation. It is thought that ceruloplasmin may be used in the mobilization of iron from intracellular stores. Here, the protein may facilitate the transfer of iron from ferritin to transferrin [Frieden and Hsieh, 1976), A relationship between copper and irtm is suggested by the fact that copper-deficient rats may develop iron deficiency anemia, as revealed by measurements of hemoglobin and hematocrit (Johnson and Dufault, 19S9 Cohen et a ., 1985), Ceruloplasmin may also function in a unique iron transport mechanism, as mentioned in the Iron section. 

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