Iron storage proteins

The very large number of known iron enzymes makes an exhaustive treatment of their chemistry unrealistic for a book such as this one. We arbitrarily decided to include only a few examples starting with heme proteins, followed by non-heme oxo-bridged proteins, iron storage proteins, and finally iron sulfur proteins. In all cases a very small segment is dedicated to the discussion of model compounds the reader is advised to review the references given in the text for further details. 

Ferritin is a globular iron-storage protein that stores iron as FeJ+. To leave the ferritin, Fe3+ must first be reduced to Fe2+. Ferritin has two types of channels through which the Fe"+ could leave a three-fold channel and a four-fold channel. The three-fold channel is lined with the amino acids aspartate (Asp) and glutamate (Glu) and the four-fold channel is lined with the amino acid leucine (Leu). Through which channel is the Fe + more likely to leave the ferritin protein Explain your answer. 

Schematic representation of ferritin, the iron storage protein, (a) The protein contains 24 neariy identical polypeptides, (b) A ribbon stmcture of one of the polypeptide chains.

C20-0105. The iron storage protein ferritin usuaiiy is neither empty of iron nor fiiied to capacity. Why is this situation advantageous for an organism ... 

Peters, S.W., Jones, B.M., Jacobs, A. and Wagstaff, M. (1985). Free iron and lipid peroxidation in the plasma of patients with iron overload. In Proteins of Iron Storage and Transport (eds. G. Spik, J. Montreuil, R.R. Crichton and J. Mazurier) pp. 321-324. Elsevier Science Publishers, New York. 

Figure 6.13 shows the Mossbauer spectra of ferritin [51], which is an iron-storage protein consisting of an iron-rich core with a diameter around 8 nm with a structure similar to that of ferrihydrite and which is surrounded by a shell of organic material. At 4.2 K essentially all particles contribute to a magnetically split component, but at higher temperatures the spectra show the typical superposition of a doublet and a sextet with a temperature dependent area ratio. At 70 K the sextet has disappeared since all particles have fast superparamagnetic relaxation at this temperature. 

Serum ferritin Less than 1 0-20 mcg/L (22-44 pmol/L) Ferritin is the protein-iron complex found in macrophages used for iron storage low in iron-deficiency anemia. 

Serum ferritin A complex protein formed in the intestine, containing about 23% iron, the amount of ferritin found in serum is directly related to iron storage in the body. 

Finally, animal, plant and microbial tissues have been shown to contain the iron storage protein ferritin. The animal protein has been extensively studied, but the mechanism of iron binding has not been completely resolved (29). Animal tissues contain, in addition, a type of granule comprised of iron hydroxide, polysaccharide and protein. The latter, called hemosiderin, may represent a depository of excess iron (30). Interestingly, a protein with properties parallel to those of ferritin has been found in a mold. Here the function of the molecule can be examined with the powerful tools of biochemical genetics (31). 

The core of the iron storage protein ferritin consists of a hydrated ferric oxide-phosphate complex. Various models have been proposed which feature Fe111 06 oct., Fe111 O4 tet. or Fe111 O4 tet. Fe111 06 oct. complexing the first listed is preferred by Gray (99) on the basis of the electronic absorption spectrum. The protein very closely related to ferritin which occurs in the mold Phycomyces blakesleeanus contains... 

In the absence of a demonstrable yeast iron-storage protein (ferritin), we have to recognize that, despite our substantial advances in understanding iron uptake in yeast, we know practically nothing about intracellular iron metabolism - except that is for iron transport into, and out of, mitochondria. 

It has been suggested (Bozzi et ah, 1997 Grant et ah, 1998) that Dps and E. inocua ferritin represent examples of a family of ancestral dodecameric protein which had as function to trap, but not to mineralize, metal ions, and that the ability to oxidize and mineralize iron efficiently and to form fourfold interactions came later. The hollow-cored dodecameric motif exemplified by Dps and E. inocua ferritin has clearly been adapted to a number of functions, since in addition to DNA binding and iron storage, other family members include a novel pilin, a bromoperoxidase and several other proteins of unknown function (Grant et ah, 1998). 

The iron storage protein ferritin is a small 20 kDa a-helical protein that spontaneously assembles into a hollow ball-like homo-24-mer. The outer diameter of the sphere is circa 12 nm and the inner diameter, or core diameter, is circa 8 nm. A smaller version, known as miniferritin or Dps protein (Dps = DNA protecting... 

Friedreich s ataxia is caused by an intronic triplet repeat expansion. Friedreich s ataxia is an autosomal recessive disorder characterized by progressive ataxia, nystagmus, distal sensory polyneuropathy and corticospinal tract degeneration. It is caused by an unstable expanded GAA repeat in intron 1 of the frataxin gene on chromosome 9ql3. This diminishes expression of frataxin, a mitochondrial iron-storage protein that participates in free radical metabolism [71]. 

Ferritin is a globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both prokaryotes and eukaryotes. Ferritin is used for immunolabeling at the electron microscope level because of its distinctive shape of the crystals and their electron density. 

Iron is stored in these proteins in the ferric form, but is taken up as Fe2+, which is oxidized by ferroxidase sites (a more detailed account of iron incorporation into ferritins is given later in this chapter). As we point out in Chapter 13, ferritins are members of the much larger diiron protein family. After oxidation, the Fe3+ migrates to the interior cavity of the protein to form an amorphous ferric phosphate core. Whereas the ferritins in bacteria appear to fulfil the classical role of iron-storage proteins, the physiological role of bacterioferritins is less clear. In E. coli it seems unlikely that bacterioferritin plays a major role in iron storage. 

There are many other proteins that contain iron in a form that is neither in haem nor in iron-sulfur clusters. We have already encountered the iron storage and transport proteins, ferritin and transferrin (see Chapter 8). We propose to discuss here two other classes of iron-containing proteins, those with mononuclear non-haem iron centres and those with dinuclear non-haem iron centres. 

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. 

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