Iron storage proteins, ferrihydrite

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. 

Ferrihydrite is the iron oxide with the most widespread distribution in living organisms. In the form of ferritin, an iron storage protein, it is found in all organisms from bacteria through to man (in heart, spleen and liver). It occurs in plants as phytoferritin (review by Seckback, 1982). Ferritin plays a key role in iron metabolism it maintains... 

Ferricytochrome c, 32 49 NIR MCD spectrum, 36 233-234 Ferrihemoproteins, reduction rates, 36 430-431 Ferrihydrite, 36 422 chemical composition, 36 455 inside apoferritin cavity, 36 459 mineralization in iron storage proteins, 36 161-164... 

Ferritin, the iron storage protein foimd in a variety of living organisms, serves two important functions. It catalyzes the oxidation of the cytotoxic Fe + ions to the less toxic Fe " " ions and it stores the insoluble Fe " " ions within its inner protein cavity in the form of a ferrihydrite-phosphate mineral core ([13, 14], see Chapters 12 and 15). The oxidation of ferrous ions is known as ferroxidase activity and the conversion of the oxidized Fe + ions into a solid state iron core is termed mineralization. The ferritin molecule is composed of 24 subunits, which are arranged to form a... 

Once the iron is inside the sphere, a site of mineral nu-cleation is located—step 2 in the biomineralization process. Although the site(s) of nucleation are not known, the walls are lined with carboxylic acids from aspartate and glutamate residues. These are the probable sites of nucleation. After nucleation, the mineral begins to form. The shape is controlled by the protein shell. Studies of the resulting mineral are consistent with octahedrally coordinated iron(III) ions joined by bridging oxide and/or hydroxide ions. A mineral termed ferrihydrite has a similar postulated structure. Because ferritin is used for iron storage agents, the supramolecular structures described in step 4 of Section III.B are not formed. 

About a quarter of the total body iron is stored in macrophages and hepatocytes as a reserve, which can be readily mobilized for red blood cell formation (erythropoiesis). This storage iron is mostly in the form of ferritin, like bacterioferritin a 24-subunit protein in the form of a spherical protein shell enclosing a cavity within which up to 4500 atoms of iron can be stored, essentially as the mineral ferrihydrite. Despite the water insolubility of ferrihydrite, it is kept in a solution within the protein shell, such that one can easily prepare mammalian ferritin solutions that contain 1 M ferric iron (i.e. 56 mg/ml). Mammalian ferritins, unlike most bacterial and plant ferritins, have the particularity that they are heteropolymers, made up of two subunit types, H and L. Whereas H-subunits have a ferroxidase activity, catalysing the oxidation of two Fe2+ atoms to Fe3+, L-subunits appear to be involved in the nucleation of the mineral iron core once this has formed an initial critical mass, further iron oxidation and deposition in the biomineral takes place on the surface of the ferrihydrite crystallite itself (see a further discussion in Chapter 19). 

A second form of storage iron is haemosiderin (Weir et al., 1984). This is deposited in humans as a response to the condition of iron overload. Haemosiderin forms as insoluble granules with electron dense cores surrounded by a protein shell. It exists in two forms primary haemosiderin is the result of iron overload due to excessive adsorption of iron in the gut, whereas the secondary form is caused by the numerous blood transfusions which are used to treat thallassaemia (a form of anaemia). Electron diffraction indicated that the iron core in primary haemosiderin is a 3-line ferrihydrite with magnetic hyperfine splitting only below 4 K and, in the secondary form, consists of poorly ordered goethite. As goethite is less soluble in ammonium oxalate buffer solution (pH 3) it has a lower intrinsic toxicity (Mann et al., 1988). 

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