Transferrin diferric

The situation prevailing in the crypt cell at the beginning of its differentiation into an enterocyte and before it has begun to climb towards the villus is shown in the lower panel. The cell s iron requirements are supplied by receptor-mediated diferric transferrin uptake from the basolateral membrane. The TfR in turn is involved in an interaction with the HFE protein, which decreases the affinity of TfR for diferric transferrin. The level of transferrin saturation, or some other factor, determines the amount of iron taken up, and presets the IRP system at a level that corresponds to the iron requirements of the organism. 

Figure 11.1 Schematic representation of iron uptake mechanisms, (a) The transferrin-mediated pathway in animals involves receptor-mediated endocytosis of diferric transferrin (Tf), release of iron at the lower pH of the endocytic vesicle and recycling of apoTf. (b) The mechanism in H. influenzae involves extraction of iron from Tf at outer membrane receptors and transport to the inner membrane permease system by a periplasmic ferric binding protein (Fbp). From Baker, 1997. Reproduced by permission of Nature Publishing Group.

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). 

Figure 7.13 The transferrin to cell cycle HOLO-TF, diferric transferrin TFR, transferrin receptor DMT1, divalent metal transporter. (From Andrews, 2000. Reproduced by permission of Nature Reviews Genetics.)...

Fig. 8. Paramagnetic enhancements to water NMRD profiles for solutions of diferric transferrin at ( ) 278 K, ( ) 293 K, (A) 308 K (35).

The H NMRD profile of the diferric transferrin solution (Fig. 5.5) [3] is also instructive for the case of a macromolecule containing a Fe(III) atom. The profile shows four inflections the first is ascribed to the cos dispersion, the second one to the transition from the dominant ZFS limit to the dominant Zeeman limit (see Section 3.7.1), the following increase is due to the field dependent electron relaxation time (see Section 3.7.2) and finally the coj dispersion appears. The best fit analysis provides the presence of a rhombic ZFS with D = 0.2, E/D = 1 /3, in accordance with EPR spectra [9]. The analysis suggests that two sets of electron relaxation times must be considered, in the range 0.3-1 x 10 9 s. In fact, Eqs. (3.11) and (3.12) are inadequate to describe the field dependence of the electron relaxation over the whole range of frequencies due to the presence of static ZFS [10]. 

Sun, IX., Garcia-Canero, R., Liu, W.,Toole-Simms, W, Crane, F.L., Morrti, DX, Low, H. (1987b). Diferric transferrin stimulates the Na+/H+ antiport of HeLa cells. Biochem. Biophys. Res. Commun. 145,467 473. 

Transferrin is a single-chain glycoprotein which has two similar binding sites for Fem ions situated in interdomain clefts in the N-terminal half (N-lobe) and C-terminal half of the molecule. Diferric transferrin is taken up by cells via receptor-mediated endocytosis. It is possible that transferrin delivers Pt to tumor cells which are known to overexpress such receptors. The combination of 1H-, 15N- and 13C-NMR spectroscopy (15N-cisplatin and 13C-Met-transferrin) has shown that one of the major cisplatin binding sites is Met-256 in the N-lobe which is solvent-accessible [51]. 

Figure 9.27 Receptor-mediated endocytosis of diferric transferrin in erythroid tissue and certain other cell lines. (Reproduced by permission from Dantry-Varsat A, Ciechanover A, Lodish HF. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sri USA 80 2258-2262, 1983.)...

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). 

Fig. 1. Schematic representation of the cycle of iron delivery to cells by transferrin, showing the uptake of diferric transferrin by cell receptors, internalization, release of iron at the lower intracellular pH, and recycling and release of apotransferrin.

Fig. 23. Visible absorption spectra for diferric transferrin complexes utilizing various synergistic anions, showing the variation in mal for the charge transfer band. Anions are 1, nitrilotriacetate 2, carbonate 3, salicylate 4, thioglycolate 5, glycine 6, glyoxy-late and 7, glycolate. From Schlabach and Bates (178), with permission.

Chidambaram, M. V., Barnes, G., and Frieden, E. (1983). Geruloplasmin and the reactions forming diferric transferrin. FEBS Lett. 159, 137-140. 

The Fe +/ + reduction potentials for holo-transferrin have been difficult to determine because of their low values and the need to take account of the dissociation of Fe(II) from diferrous-transferrin. This has been estimated from the association constant for Fe(II) binding to transferrin at pH 7.4, 10 M, which yields reduction potentials < —500 mV at pH 7.4 for the C-terminal and N-termtnal sites of human serum transferrin, and probably more negative potentials at the lower pH present in the endosome where iron is released. ... 

As noted in Section 3, some pathogenic bacteria have transferrin receptors on their outer membranes to acquire diferric transferrin from their host. These outer membrane receptors extract the iron from the transferrin and transport it into the periplasm where it is picked up by the periplasmic ferric binding proteins (Fbp), which carry the iron to a transmembrane protein in the inner membrane that conveys it into the cytoplasm. A considerable amount of chemical and structural information has been gathered for Fbp, which is sometimes referred to as bacterial transferrin in recognition of its similarities with animal transferrin. ... 

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