Transferrin and

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). 

Three forms of folate appear to be transported ia the blood foHc acid, folate loosely bouad to low affinity binder semm proteins (such as albumin, a-macroglobulin, and transferrin), and folate bound to high affinity protein binders. Approximately 5% of total semm folate is being transported by high... 

Aguas, A., Esaguy, N., Sunkel, C.E., Silva, M.T. (1990). Cross-reactivity and sequence homology between the 65 kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect. Immun. 58, 1461-1470. 

F9 embryonal carcinoma cells have a simple set of growth supplements which are required for growth in serum-free medium insulin, transferrin, and fibronectin (Rizzino and Sato, 1978). Fibronectin is a component of the extracellular matrix and facilitates the attachment of the cells to the culture dish. In addition, high density lipoprotein (HDL) has been observed to promote the growth of F9 cells serum-free. 

Gutteridge, J.M.C. (1987). Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular activities of caeruloplasmin, transferrin and lactoferrin. Biochem. J. 245, 415-421. 

Monteiro, H.P. and Winterbourne, C.C. (1988). The superoxide-dependent transfer of iron from ferritin to transferrin and lactoferrin. Biochem. J. 256, 923-928. 

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

Total iron-binding capacity (TIBQ—quantifies the ironbinding capacity of transferrin and is increased in iron-deficiency anemia... 

We will deal here only with proteins of class (ii) that contain diiron centres and reserve the discussion of proteins containing polyiron oxo aggregates (ferritins) until Chapter 6. As for the proteins of class (iii), their discussion is deferred until Chapter 3 concerning siderophore receptors and Chapter 5 concerning the transferrins and their receptors respectively. 

FhuA and FepA will prove to be the reference structures for a large group of bacterial outer-membrane transporters that take up bacterial Fe3+-siderophores, Fe3+ released from host transferrin and lactoferrin, haem, and haem released from haemoglobin and haemopexin. It is assumed that all iron sources are transported... 

The majority of Fur-regulated gene products are involved in iron uptake. Genes for transport and biosynthesis of enterobactin have been studied in E. coli K-12 (Earhart, 1996). It is assumed that this system is found in nearly every E. coli strain. Also the ferrichrome transport system seems to have a very broad distribution. The ferric citrate transport system (fee), however, is only present in some E. coli strains and may be part of a pathogenicity island. The aerobactin and yersiniabactin biosynthesis and transport systems are not found in all E. coli strains and are integrated into pathogenicity islands (Schubert et al., 1999). The ability to utilize haem seems also to be a specific pathogenicity-related adaptation. Haem transport systems are used in the animal or human host, where transferrin and lactoferrin create an iron-poor environment for bacteria. 

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... 

The iron-binding sites have been characterized by crystallographic studies on several transferrins, and in Figure 5.7 (Plate 7) that of the N-lobe of human lactoferrin is presented. The 3+ charge on the ferric ion is matched by the three anionic ligands Asp-63, Tyr-95 and Tyr-188 (the fourth, His-249, is neutral), while the charge on the carbonate anion is almost matched by the positive charge on Arg-124 and the... 

Katz, H. J. (1970). Transferrin and its function in the regulation of iron metabolism, page 539 in Regulation of Hematopoiesis, Vol. 1, Gordon, A. D., Ed. (Appleton-Century-Crofts, New York). 

Matsumoto et al. demonstrated that the removal of iron from diferric transferrin by the tris-hydroxamate siderophore mimic TAGE occurs in two discreet steps (90). The slower step corresponds to iron removal from the more stable C-lobe site on transferrin and the faster step to removal from the N-lobe. The rates of removal are similar to the rates of removal of iron from diferric transferrin by desferrioxamine B (4), signifying similar mechanisms of removal between the two systems (90). 

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