Transferrins transferrins

Once in the serum, aluminium can be transported bound to transferrin, and also to albumin and low-molecular ligands such as citrate. However, the transferrrin-aluminium complex will be able to enter cells via the transferrin-transferrin-receptor pathway (see Chapter 8). Within the acidic environment of the endosome, we assume that aluminium would be released from transferrin, but how it exits from this compartment remains unknown. Once in the cytosol of the cell, aluminium is unlikely to be readily incorporated into the iron storage protein ferritin, since this requires redox cycling between Fe2+ and Fe3+ (see Chapter 19). Studies of the subcellular distribution of aluminium in various cell lines and animal models have shown that the majority accumulates in the mitochondria, where it can interfere with calcium homeostasis. Once in the circulation, there seems little doubt that aluminium can cross the blood-brain barrier. 

Li H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev 2002 22(3) 225-250. 

Transferrin. Transferrin produces specific biological functions. It behaves as a substantial inflammatory marker, and its concentration rises in... 

Transferrin Transferrin receptor Tumor cells/tumor, and crossing of blood-brain barrier [60,87,88]... 

A salient feature of the receptor-mediated transferrin-to-cell endocytic cycle in human iron metabolism is the persistence of the transferrin-transferrin receptor... 

Figure 2.8 compares corrected Nernst plots for C-lobe half-transferrin free in solution and bound to the transferrin receptor, at endosomal pH. These data clearly demonstrate that docking iron-loaded C-lobe transferrin at the transferrin receptor at pH 5.8 makes it energetically more favourable to reduce Fe " to Fe by 200 mV. Furthermore, receptor-docking places Fe reduction in a range accessible to NADH or NADPH cofactors, consistent with the hypothesis that reduction is the initial event in iron release from transferrin in the endosome. Fe " is bound by /zTf at least 14 orders of magnitude more weakly than Fe, so that reductive release of iron bound to HTi in the transferrin-transferrin receptor complex is then physiologically and thermodynamically feasible, and the barrier to transport across the endosomal membrane is lifted. The transferrin receptor, therefore, is more than a simple conveyor of... 

Li H, Sun H, Zhong MQ. The role of the transferrin-transferrin-receptor system in drug delivery and targeting. Trends Pharmacol Sci 2002 23 206-209. 

Total-body iron of a 70-kg adult is about 4.2-4A g. The distribution of iron in various body compartments is given in Table 29-1. The key players of iron metabolism include iron-responsive elements of appropriate mRNAs, iron regulatory proteins divalent metal transporter 1, major histocompatibility complex (MHC) class I-like protein designated as HFE protein, d2-microglobulin, transferrin, transferrin receptor, and ferritin. 

The bulk of transferrin iron is delivered to immature erythroid cells for utilization in heme synthesis. Iron in excess of this requirement is stored as ferritin and hemosiderin. Unloading of iron to immature erythroid cells is by receptor-mediated endocytosis. The process begins in the clathrin-coated pits with the binding of diferric transferrin to specific plasma membrane transferrin receptors that are associated with the HFE protein complex. The next step is the internalization of the transferrin-transferrin receptor-HFE protein complex with formation of endosomes. The iron transporter DMTl present in the cell membrane is also internalized into the endosomes. In the endosomes, a proton pump acidifies the complex to pH 5.4, and by altering conformation of proteins, iron is released from transferrin bound to transferrin receptor... 

Because free iron is toxic, it is usually found in the body bound to proteins (see Fig. 44.6). Iron is carried in the blood (as Fe ) by the protein apotransferrin, with which it forms a complex known as transferrin. Transferrin is usually only one-third saturated with iron. The total iron-binding capacity of blood, mainly due to its content of transferrin, is approximately 300 pig/dL. 

Transferrin Transferrin receptor 3.3 X 10 50,000/HepG2 cell Reported in [21]... 

The evidence that ceruloplasmin (Cp) (E.C. 1.12.3,1) is a direct molecular link between copper and iron metabolism is summarized. Copper deficiency results in low plasma Cp and iron, reduced iron mobilization, and eventually anemia, even with high iron storage in the liver. Cp controls the rate of iron uptake by transferrin. Transferrin plays a key role in the availability of iron for the biosynthesis of hemo-globin in the reticulocytes. The ferroxidase activity of Cp results in the reduction of free iron ion generating a conr centration gradient from the iron stores to the capillary system, thus promoting a rapid iron efflux in the reticuloendothelial system. It has been confirmed both in vivo and in the perfused liver that lOr M Cp specifically induces a rapid rise in plasma iron. 

Outline the role of RNA secondary structure in the regulation of iron metabolism in animals. Describe the roles of transferrin, transferrin receptor, ferritin, the iron-response element, and IRE-binding protein. Relate the IRE-binding protein to aconitase and iron sensing. 

Adrenocorticotropic hormone, a-amylase, atrazineAriazines, 2,4-dinitrophenyl lysine, human chorionic gonadotropin, human serum albumin, immunoglobulin G, isoproturon, parathyroid hormone, testosterone, theophylline, thyroid stimulating hormone, thyroxine, transferrin, transferrin, trinitrotoluene... 

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