Transferrin plasma

It seems clear that complexes 28 and 29 both enter cancer cells by transferrin-mediation. Tumor cells are known to have a high density of transferrin receptors, and this provides a route for the uptake of ruthenium (175). In normal blood plasma, transferrin is only one-third saturated with Fe(III) and therefore vacant sites are available for Ru(III) binding. Baker et al. have shown by X-ray crystallography that complex 29 binds to His-253 of apolactoferrin, one of the Fe(III) ligands in the iron binding cleft of the N-lobe, with displacement of a chloride ligand (176). Ruthenium(III) is well known to have a high affinity for solvent-exposed His side chains of proteins (177). Complex... 

Physiologically, body stores are maintained by extracting approximately 10% of the iron provided in a balanced diet and this corresponds to 1.5 mg each day for males and slightly more for females to compensate for pregnancy and menses. The trace element is derived from food by peptic digestion and after reduction the ferrous form crosses the enterocyte to be released at the serosal pole via the ferroportin-hepcidin mechanism to be transported, by plasma transferrin, to developing red cells in the marrow for haemoglobin synthesis. At the end of their life span effete erythrocytes are removed by the reticuloendothelial system in the spleen, bone marrow and the liver. 

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. 

The entrance of iron into the body through the intestinal mucosal cells may involve the transferrin present in those cells44 and the influx of iron may also be regulated by blood plasma transferrin. There is also a nontransferrin pathway.42 55... 

Very little is known about the transport of nickel, manganese and cobalt. Plasma transferrin, conalbumin and citrate have been suggested to serve as carrier ligands. Transferrin is the main transport protein for vanadium in humans, and will transfer vanadium to ferritin. 

In the bloodstream, ferric iron binds tightly to circulating plasma transferrin (TF) to form diferric transferrin (FeTF). Absorption of iron into erythrocytes depends on basolateral membrane receptor-mediated endocytosis of FeTF by transferrin receptor 1 (TfR 1). FeTF binds to TfR 1 on the surface of erythroid precursors. These complexes invaginate in pits on the cell surface to form endosomes. Proton pumps within the endosomes lower pH to promote the release of iron into the cytoplasm from transferrin. Once the cycle is completed,TF and TfR 1 are recycled back to the cell surface. TF and TfR 1 play similar roles in iron absorption at the basolateral membrane of crypt enterocytes (Parkilla et al., 2001 Pietrangelo, 2002). 

Transferrin binds to Al + and is the main protein carrier of Al + in the plasma. Displacement of the 10 times stronger binding Fe + is unnecessary because plasma transferrin is about 50 qM in unoccupied sites. On the basis of values of requisite stability constants, it was suggested that in blood plasma about 89% of Al + is bound to transferrin and 11% to citrate. This distribution is supported by direct measurements by a variety of methods. ... 

Figure 20-4 Proposed function of ceruloplasmin copper (CpCu " ) as a proton (hydrogen ion) recipient from cellular ferrous iron.The resulting oxidation of Fe to the ferric state permits its binding and transport by plasma transferrin. CpCu" is oxidized (regenerated to CpCu ) by reaction with oxygen, oxidized thiol groups, or other oxidizing substances, (Modified from Johnson AM. Ceru/op/osm/n. In Ritchie RF, Navolotskaia 0, editors. Serum proteins in clinical medicine. Vol. I Laboratory section. Scarborough, ME Foundation for Blood Research, 1996 13.01-13.03.)...

Because CSF is mainly an ultrafiltrate of plasma, low molecular weight plasma proteins such as prealbumin, albumin, and transferrin normally predominate. No protein with a molecular weight greater than that of IgG is present in sufficient concentration to be visible on electrophoresis. The electrophoretic pattern of normal CSF after concentrating the fluid has two striking features—a prominent prealbumin band and two transferrin bands. The second of the electrophoretic transferrin bands is the x (tau) protein band, which is produced or transformed intrathecally and, by comparison with plasma transferrin, is deficient in sialic acid content. 

Intestinal absorption of is low, ranging from 0.4% to 2.5%, so fecal output is mainly unabsorbed dietary chromium. Absorption is increased marginally by ascorbic acid, amino adds, oxalate, and other dietary factors. After absorption, chromium binds to plasma transferrin with an affinity similar to that of iron. It then concentrates in human liver, spleen, other soft tissue, and bone. Urine chromium output is around 0.2 to 0.3 U,g/day, the amount excreted being to some extent dependent upon intake. Paradoxically, urine output appears to be relatively increased at low dietary levels. Thus 2% is lost in urine at an intake of lOpg/day, but only 0.5% at an intake of 40pg/day. Both running and resistive exercise increases urine chromium excretion. 

Trinder D, Olynyk JK, Sly WS, Morgan EH. Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Proc Nad Acad Sci USA 2002 99 5622-6. 

Plasma transferrin levels are commonly measured in the evaluation of disorders of iron metabolism (see below). It is customary to measure transferrin concentration... 

Transferrin is one of the proteins responsible for binding and transporting both iron and manganese throughout the body. One study (Vahlquist et al. 1975) reported no correlation between infant cord blood and maternal blood transferrin levels. The same study reported an increase in plasma transferrin from 1.68-H/-0.60 mg/mL in blood from infants at 6 weeks of age, to a peak of 2.60+1-0.21 mg/mL at 10 months, with values stabilizing at these adult levels throughout 16 years of age. The authors did not comment as to the statistical difference, if any, of these values. 

Hosain E, McIntyre PA, Poulose K, Stern HS and Wagner NH (1969) Binding of trace amounts of ionic indium-113m to plasma transferrin. Clin Chim Acta 24 69-75. 

In humans, hemoglobin concentration and hematocrit provide information about iron utilization in erythropoiesis. These parameters, however, can be confounded by inflammation, pregnancy, dehydration, polycythemia, hemoglobinopathies, and by deficiencies of vitamin B12 or folic acid (Gibson 1990). Plasma ferritin reflects body iron stores, but is also confounded by inflammation, liver diseases, leukemia, Hodgkin s disease, or alcohol intake. Transferrin saturation and plasma transferrin receptor are valuable parameters to support the diagnosis of iron deficiency and ineffective erythropoiesis (Thorstensen and... 

Regulation of transcription by iron. A cell s ability to acquire and store iron is a carefully controlled process. Iron obtained from the diet is absorbed in the intestine and released into the circulation, where it is bound by transferrin, the iron transport protein in plasma. When a cell requires iron, the plasma iron-transferrin complex binds to the transferrin receptor in the cell membrane and is internalized into the cell. Once the iron is freed from transferrin, it then binds to ferritin, which is the cellular storage protein for iron. Ferritin has the capacity to store up to 4,000 molecules of iron per ferritin molecule. Both transcriptional and translational controls work to maintain intracellular levels of iron (see Figs. 16.23 and 16.24). When iron levels are low, the iron response element binding protein (IRE-BP) binds to specific looped structures on both the ferritin and transferrin receptor mRNAs. This binding event stabilizes the transferrin receptor mRNA so that it can be translated and the number of transferrin receptors in the cell membrane increased. Consequently, cells will take up more iron, even when plasma transferrin/iron levels are low. The binding of IRE-BP to the ferritin mRNA, however, blocks translation of the mRNA. With low levels of intracellular iron, there is little iron to store and less need for intracellular ferritin. Thus, the IRE-BP can stabilize one mRNA, and block translation from a different mRNA. 

Most of the common immunological techniques (nephelometry, turbidimetry, etc.) can be used to determine the concentration of transferrin directly. Generally, enhanced turbidimetric assays are now used for transferrin measurements on automated analyzers. Transferrin is decreased in disorders involving reduced or altered protein synthesis (e.g., liver disease) and increased in iron deficiency anemia. A rare condition of near complete absence of plasma transferrin (atransferrinemia) has been reported. 

Transferrins or siderophilins are a group of iron binding glycoproteins found in plasma. They can be concentrated by electrophoresis or alcohol precipitation. The electrophoretic mobility of transferrins is that of -globulin after alcohol fractionation of plasma, transferrins are found in fraction IV. Transferrins contain 0.13% iron, and it is estimated that each protein molecule (mol wt 90,000) forms strong ionic bonds with two atoms of iron to yield a salmon pink complex with an absorption maximum at 460-470 mp. 

Ferrous ions transferred into the blood are oxidised to ferric ions and then enter into the molecule of a transport protein under the catalysis of ferro oxidase ceruloplasmin, the main plasma metaUoprotein containing copper. Transferrin ensures the transfer of iron to all tissues. Under normal conditions, about 30% of plasma transferrin is saturated with iron, and the remainder is apotransferrin. The target tissue captures transferrin by specific receptors and iron is immediately available for the synthesis of proteins and other haem metalloproteins or temporarily stored in ferritin. A substantial portion of the transported iron from transferrin is taken away in the bone marrow for the production of erythrocytes. New erythrocytes absorb the whole transferrin molecules. The release of iron from transferrin occurs due to a lower pH compared with the pH in the extracellular space. Apotransferrin is then released from the erythrocytes and iron is built into the... 

Gorinsky, B, Horsburgh, C., Lindley, P, F., Moss, D. S., Parkar, M., and Watson, J. L, (1979) Evidence for the bilobal nature of diferric rabbit plasma transferrin. Nature 281 157-158,... 

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