Plasma protein transferrin

Oral iron therapy should not be given 24 h before i.m. injections begin and for 5 days after the last i.v. injection not only is continuation unnecessary, but it may promote adverse reactions by saturating the plasma protein (transferrin) binding capacity so that the injected iron gives a higher unbound plasma iron concentration than is safe. 

Internal exchange of iron is accomplished by the plasma protein transferrin. This 76 kDa /Ij-glycoprotein has 2 binding sites for ferric iron. Iron is delivered from transferrin to intracellular sites by means of specific transferrin receptors in the plasma membrane. The iron-transferrin complex binds to the receptor, and the ternary complex is taken up by receptor-mediated endocytosis. Iron subsequently dissociates in the acidic, intracellular vesicular compartment (the endosomes), and the receptor returns the apotransferrin to the cell surface, where it is released into the extracellular environment. Cells regulate their expression of transferrin receptors and intracellular ferritin in response to the iron supply. Apoferritin synthesis is regulated post-transcriptionally by 2 cytoplasmic binding proteins (IRP-1 and lRP-2) and an iron-regulating element on its mRNA (IRE). 

A further prerequisite for an indium complex to be useful for nuclear medicine applications is that it be resistant to exchange with the plasma protein transferrin. Indium binds to transferrin at the Fe binding site with a stability constant (/f ) of lO in the presence of bicarbonate [7]. The formation constants of indium with ethylenediaminetetraacetic acid (EDTA) (log = 25.0) and DTPA (log Ki = 29.0) are such that at infinite dilution equilibrium would favor the formation of indium transferrin [8J. The slow dissociation of indium from these complexes hinders the formation of indium transferrin. 

Table 50-2 summarizes the functions of many of the plasma proteins. The remainder of the material in this chapter presents basic information regarding selected plasma proteins albumin, haptoglobin, transferrin, ceruloplasmin, aj-antitrypsin, aj i roglobulin, the immunoglobulins, and the complement system. The lipoproteins are discussed in Chapter 25. 

Transferrin (Tf) is a plasma protein that plays a centtal role in transporting iron around the body to sites where... 

This receptor-mediated endocytotic pathway has been especially well studied in the uptake of iron from blood plasma. Iron, because of its very low-solubility product (< 1(T17 at pH 7.4), is transported in plasma bound to the iron-binding protein transferrin. Two Fe3+ ions bind to each transferrin molecule. Entry into... 

Another example is uptake of the iron-containing protein, transferrin, which circulates in the blood. It binds to its receptor to form a complex that enters the cell via endocytosis. The iron is then released from the endosome for use in the cell (e.g. haemoglobin formation for erythrocyte production or cytochrome production in proliferating cells). The number of transferrin receptors in the plasma membrane increases in proliferating cells and the number in the liver is increased by cytokines during infection. This results in a lower concentration of iron in the blood which decreases the proliferation of invading pathogens (Chapters 15 and 18). 

Iron ion The protein transferrin binds ferric ions and transports them in the semm aronnd the body. The ions are taken np by cells via a transferrin receptor which is present in the plasma membrane. The receptor binds transferrin and the complex enters the cell where transferrin releases... 

Brunet, M.J., Blade, C., Salvado, M.J., and Arola, L., Fluman apo A-I and rat transferrin are the principal plasma proteins that bind wine catechins, J. Agric. Food Chem., 50, 2708, 2002. 

Major plasma proteins serum albumin, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL), immunoglobulins (hundreds of kinds), fibrinogen, prothrombin, many specialized transport proteins such as transferrin... 

Iron for biosynthesis is transported through the bloodstream by the protein transferrin. The following procedure measures the Fe content of transferrin 10 This analysis requires only about 1 p,g for an accuracy of 2-5%. Human blood usually contains about 45 vol% cells and 55 vol% plasma (liquid). If blood is collected without an anticoagulant, the blood clots, and the liquid that remains is called serum. Serum normally contains about 1 pg of Fe/mL attached to transferrin. 

Putnam, F. W. 1975. Transferrin. In The Plasma Proteins, Vol. I. F. W. Putnam (Editor). Academic Press, New York. 

Boado et al. [28] devised delivery systems based on conjugates of streptavidin and the 0X26 monoclonal antibody directed to the transferrin receptor as a carrier for the transport of ASO. These delivery systems were found to transport peptide nucleic acid antisense molecules, but not ASO, across the BBB. These authors attributed this difference to preferential binding of phosphorothioate oligonucleotide to plasma protein instead of the antibody complex, which reduced their transport. 

The majority of body iron is not chelatable (iron from cytochromes and hemoglobin). There are two major pools of chelatable iron by DFO (19). The first is that delivered from the breakdown of red cells by macrophages. DFO competes with transferrin for iron released from macrophages. DFO will also compete with other plasma proteins for this iron, when transferrin becomes saturated in iron overload. The quantity of chelatable iron from this turnover is 20mg/day in healthy individuals and iron chelated from this pool is excreted in the urine (19). The second major pool of iron available to DFO is derived from the breakdown of ferritin and hemosiderin. The ferritin is catabolized every 72 hours in hepatocytes, predominantly within lysosomes (I). DFO can chelate iron that remains within lysosomes shortly after ferritin catabolism or once this iron reaches a dynamic, transiently chelatable, cytosolic low-molecular-weight iron pool (20). Cellular iron status, the rate of uptake of exogenous iron, and the rate of ferritin catabolism are influent on the level of a labile iron pool (21). Excess ferritin and... 

Ascorbate is also active in the reduction of Fe + in the plasma transport protein, transferrin, to Fe + for storage in ferritin in the Uver or for heme synthesis. It is not clear to what extent this represents specific actions of ascorbate, because other reducing reagents, including glutathione, also enhance heme synthesis, and the NADH-dependent flavoprotein ferriductase is the major factor controlling the transfer of iron between transferrin and ferritin. 

The specific interaction of Cibacron Blue and its derivatives to dinucleotides, mainly to NAD, NADP and ATP offers the possibility of purifing all enzymes which are dependent on these coenzymes. According to Mosbach < - > there are 163 enzymes requiring NAD, 141 enzymes requiring NADP, about 40 enzymes requiring NADP or NAD and 225 enzymes dependent on ATP. Besides these specific interactions non-specific interactions of Cibacron Blue and its derivatives with. proteins can also be applied for separation purposes. The non-specific interaction of Cibacron Blue with human serum albumin, for instance, enables albumin to be removed from transferrin, ceruloplasmin or other plasma proteins in order to purify human... 

---