Cellular Iron Uptake

The Tf-TfR cycle. The plasma protein Tf binds to two ferric iron with high affinity. Once Tf-Fe is recognized by its receptor, TfR, it triggers endocytosis. The internalized vesicles become acidified by the proton pump. As the pH decreases in the endosomes, the structure of Tf-TfR complex changes and ferric iron releases. The newly identified endosomal reductase, STEAP3 converts ferric iron to the ferrous form, which is then transported out of endosomes. The fate of the iron after it leaves the endosomes is less well known. Eventually, iron will be used for metabolic processes, such as heme protein synthesis and iron-sulfur (Fe-S) assembly. The apo-Tf TfR will be recycled to the cell membrane. 

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Li J, Kogan M, Knight SAB, et al. 1999. Yeast mitochondrial protein, Nfslp, coor-dinately regulates iron-sulfur cluster proteins, cellular iron uptake, and iron dis-tribntion. J Biol Chem 274 33025-34. 

Incubation of Pseudomonas putida with anthracene-labeled carbon-base ferrichrome analog Fe(lll) complex 173 resulted in cellular iron uptake and the appearance of anthracene fluorescence in the culture medium identical to the Fe-ferrichrome uptake. Incubation with the alanyl analog 174 failed to show any significant iron uptake or fiuorescence. This is consistent with the tests described above on the unlabeled analogs. Remarkably, other strains such as Pseudomonas fluorescens S680 or WCS3742 also did not show any iron uptake or culture fluorescence. 

Muldtopadyay. C-, Attieh, and Fox, II L. (1998). Kolc of ceruloplasmin in cellular iron Uptake. Serfner 279, 714-717. 

FIGURE 8.17 Schematics of cellular iron uptake and utilisation. Adapted from Richardson et al., 2010.)... 

Singh A, Mohan ML, Isaac AO, Luo X, Petrak J, Vyoral D, Singh N (2009) Prion protein modulates cellular iron uptake a novel function with implications for prion disease pathogenesis. PLoS ONE 4 e4468... 

PiREZ G, Garbossa G, Di Risio C, Vittori D and Nesse a (2001) Disturbance of cellular iron uptake and utilisation by aluminium. J Inorg Biochem 87 21-27. 

Crichton R (2001b) Cellular iron uptake in mammals. In Crichton R, ed. Inorganic Biochemistry of iron Metabolism, 2nd edn, pp. 107-132. John Wiley Sons, Chichester. 

Thorstensen, K. and Romslo, 1. (1990) The role of transferrin in the mechanism of cellular iron uptake. Biochem. J. 271 1-10. 

The rate of synthesis of erythroid ALAS, the first enzyme of the heme biosynthetic pathway, is directly dependent on the cellular iron concentration. Clinically, mutations in the ALAS2 gene are associated with XLSA. Although the cellular iron uptake systems remain completely functional in XLSA patients, this type of side-... 

Eukaryotic phytoplankton do not appear to produce siderophores and there is little evidence for direct cellular uptake of ferric siderophore chelates. Instead there is mounting evidence for the utilization of a high-affinity transport system that accesses ferric complexes via their reduction at the cell surface and subsequent dissociation of the resulting ferrous-ligand complexes. The released ferrous ions bind to iron(ii) receptors on iron transport proteins located on the outer cell membrane, which transport the iron into the cell. This intracellular transport involves the reoxidation of bound iron(ii) to iron(iii) by a copper protein, and thus copper is required for cellular iron uptake. The availability of iron to this transport... 

Acknowledgements. Work on cellular iron uptake and removal in the author s laboratory is supported by grants from the Medical Research Council of Canada and the Heart and Stroke Foundation of Ontario. 

Ferrireductases and ferroxidases Ceruloplasmin (Cp) Duodenal cytochrome b Hephaestin Steap proteins Plasma protein with ferroxidase activity involving in cellular iron export Membrane ferric reductase involving in cellular iron uptake Membrane Cp homolog functioning in enterocyte iron export Ferrireductases required for iron uptake in Tf cycle... 

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