Iron in plasma

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. 

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]. 

The bleomycin assay has been applied to assess the levels of available, nontransferrin-bound iron in plasma samples in patients with iron overload disease (Peters et al., 1985), with acute leukaemia before and after drug chemotherapy (Halliwell et al., 1988), as well as patients with rheumatoid arthritis (Winyard et al., 1987). 

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

The level of soluble iron in plasma is raised in cases of iron overload, with iron being bound to proteins, transferrin, and albumin, and with... 

Serotransferrin, two thirds of which is iron-free in normal plasma, may intervene in the defence of organisms against bacteria due to its ability to bind iron so tighly under physiological conditions that the concentration of free ionic iron in plasma and lymph... 

Plasma iron is derived mainly from the breakdown of hemoglobin in the reticuloendothelial system. Transferrin reversibly binds iron very firmly - there are no free iron ions present in plasma as they would be very toxic. Molecules of the transferrin-iron complex combine with receptor sites on erythroblasts and are then internalized, releasing iron into the cytosol. Consequently, the first stage in the measurement of iron in plasma (or serum) is dissociation of... 

Grootveld M, Bell JD, Halliwell B, Aruoma OI, Bomford A, Sadler PJ (1989) Nontransferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J Biol Chem 264 4417-4422 Gyparaki M, Porter JB, Huehns ER, Hider RC (1986) Evaluation in vivo of hydro-xypyrid-4-one iron chelators intended for the treatment of iron overload by the oral route. Biochem Soc Trans 14 1181-1181 Hallaway PE, Eaton JW, Panter SS, Hedlund BE (1989) Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci USA 86 10108-10112... 

Free iron ions are very toxic. So, the iron molecule is always transported in combination with protein 2 atoms of ferric iron are bound to 1 molecule of beta globulin protein called transferring—and the combination forms transferritin. When the level of iron ions exceeds the binding capacity of the transferrin, iron toxemia occurs. Normally, the amount of iron in plasma is sufficient to bind only 1/3 of the transferring—the remaining 2/3 represents the unbound reserve. 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

The concentration of transferrin in plasma is approximately 300 mg/dL. This amount of transferrin can bind 300 pg of iron per deciliter, so that this represents the total iron-binding capacity of plasma. However,... 

Ferritin is another protein that is important in the metabolism of iron. Under normal conditions, it stores iron that can be called upon for use as conditions require. In conditions of excess iron (eg, hemochromatosis), body stores of iron are greatly increased and much more ferritin is present in the tissues, such as the liver and spleen. Ferritin contains approximately 23% iron, and apoferritin (the protein moiety free of iron) has a molecular mass of approximately 440 kDa. Ferritin is composed of 24 subunits of 18.5 kDa, which surround in a micellar form some 3000-4500 ferric atoms. Normally, there is a little ferritin in human plasma. However, in patients with excess iron, the amount of ferritin in plasma is markedly elevated. The amount of ferritin in plasma can be conveniently measured by a sensitive and specific radioimmunoassay and serves as an index of body iron stores. 

There is very little data on ROM production in haemochromatosis in humans. Increases in thiobarbituric acid reactants in plasma were associated with increases in non-transferrin-bound free iron. However, other indices of lipid peroxidation were no different from controls (Peters eta/., 1985). There are no studies of in vivo lipid peroxidation in humans. It is also of interest that levels of antioxidant defences in liver biopsies from patients with haemochromatosis are normal (Selden et /., 1980). 

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.

Figure 8.1 Body iron stores and daily iron exchange. The figure shows a schematic representation of the routes of iron movement in normal adult male subjects. The plasma iron pool is about 4 mg (transferrin-bound iron and non-transferrin-bound iron), although the daily turnover is over 30 mg. The iron in parenchymal tissues is largely haem (in muscle) and ferritin/haemosiderin (in hepatic parenchymal cells). Dotted arrows represent iron loss through loss of epithelial cells in the gut or through blood loss. Numbers are in mg/day. Transferrin-Tf haemosiderin - hs MPS - mononuclear phagocytic system, including macrophages in spleen and Kupffer cells in liver.

The peculiar thing in hereditary haemochromatosis (HH) is that the intestinal mucosal cell behaves essentially like an iron deficient cell. Iron absorption is always high if related to the body s iron needs. In HH subjects with normal plasma ferritin values, both mucosal uptake and mucosal transfer of iron often exceed values found in patients with uncomplicated iron deficiency (Marx, 1979b). In fact the situation with respect to iron absorption in mature intestinal mucosal cells, as depicted in Figure 9.4(b), is identical to that in iron deficiency, except for the difference in plasma iron saturation. It was already known that mucosal cells in HH contain no ferritin, explaining the high mucosal transfer of iron (Francanzani... 

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... 

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