Ferritin core

We can briefly conclude that the mineralization process of iron in ferritin cores is a difficult process to follow experimentally. While we believe that iron is delivered for storage within the protein cavity as Fe(II), and that an oxidation step occurs in the formation of the ferritin iron core, it is not clear what percentage of iron oxidation occurs on the growing surface of the mineral and what at the catalytic ferroxidase... 

Figure 19.5 Representation of the crystal growth mechanism for ferritin core formation. (From Lewin et al., 2005. Copyright with permission from The Royal Society of Chemistry, 2005.)...

Why mammalian ferritin cores contain ferrihydrite-like structures rather than some other mineral phase is less easy to understand, and presumably reflects the way in which the biomineral is built up within the interior of the protein shell together with the geometry of the presumed nucleation sites. The phosphate content in the intracellular milieu can readily be invoked to explain the amorphous nature of the iron core of bacterioferritins and plants. Indeed, when the iron cores of bacterioferritins are reconstituted in the absence of phosphate, they are found to be more highly ordered than their native counterparts, and give electron diffraction lines typical of the ferrihydrite structure. Recently it has been reported that the 12 subunit ferritin-like Dps protein (Figure 19.6), discussed in Chapter 8, forms a ferrihydrite-like mineral core, which would seem to imply that deposition of ferric oxyhydroxides within a hollow protein cavity (albeit smaller) leads to the production of this particular mineral form (Su et al., 2005 Kauko et al., 2006). 

Ferritin iron cores, or polynuclear iron complexes in lipid vesicles or in matrices of protein and complex carbohydrates, appear to be the precursors of minerals such as hematite and magnetite that form in certain bacteria (31), marine Invertebrates (22), insects, and birds. The conversion from ferrltin-llke iron cores requires partial changes in the oxidation state of and/or ordering of the iron atoms, and may depend on some of the natural variations in ferritin core structure. 

The function of all ferritin molecules is to store iron. However, the mechanisms by which iron enters the core or is released from the core 1ji vivo is poorly understood. Experimentally, Fe(II), but not Fe(III), mixed with ferritin protein coats forms normal iron cores. Moreover, reductants such as thloglycollate or reduced flavins can reverse the process of core formation and release Fe(II) from the core. Since such reductants occur in vivo, reduction of ferritin cores may also occur vivo. 

Models for Nucleatlon of Ferritin Cores. A number of small... 

Since the (Fen05(0H)6> unit is stable, it has been speculated(8b,17b) that it might also be present in the ferritin core. Since the majority of phosphate in ferritin is adventitious, surface bound and the metallic core can be reconstituted in the absence of phosphate groups with no change in the X-ray powder diffraction pattem(l), replacement of bridging phosphate by bridging carboxylate groups should not influence the three dimensional structure of the core. Calculations show that -409 Fell nnits could fill the apoferritin inner cavity. Further details can be found in reference 17. 

It can be concluded that Fe(III) can generate a diversity of structural types despite the apparent low "plasticity of its coordination sphere. In only one case, 6, is the metal less than octahedrally coordinated. The presence of structural invariants like the kernel of tetranuclear aggregates suggest the possibility that some substructures are favored and therefore likely to occur in other, yet unknown, aggregates or even in the ferritin core. 

Mann, S. Bannister, J.V. Williams, R.J.P. (1986 a) Structure and composition of ferritin cores isolated from human spleen, limpet (patella vulgata) hemolymph and bacterial (Pseudomonas aeruginosa) cells. J. Mol. Biol. 188 225-232... 

Iron can be deposited in ferritin by allowing apoferritin to stand with an Fe(II) salt and a suitable oxidant, which may be 02. Physiological transfer of Fe(III) from transferrin to ferritin is thought to require prior reduction to Fe(II). The reoxidation by 02 to Fe(III) for deposition in the ferritin core (Eq. 16-2) is catalyzed by ferrooxidase sites located in the centers of the helical bundles of the H-chains.70-73... 

St. Pierre, T. G. Chan, R Bauchspiess, K. R. Webb, J. Betteridge, S. Walton, S. Dickson, D. P. E. Synthesis, structure and magnetic properties of ferritin cores with varying composition and degrees of structural order models for iron oxide deposits in iron-overload diseases. Coord. Chem. Rev. 1996, 151, 125-143. 

Wajnberg, E. El-Jaick, L.J. Linhares, M.P. Esquivel, D.M. Ferromagnetic resonance of horse spleen ferritin core blocking and surface ordering temperatures. J. Magn. Reson. 2001, 153(1), 69-74. 

A variety of approaches have been adopted in attempts to obtain analogs of crystalline ferritin cores but, as Powell has pointed out, uncertainty over the structure of the ferritin core itself complicates this field. The earliest synthetic approach was that of Spiro et al., who obtained citrate-coated spheres of polymeric iron hydroxide by hydrolysis of ferric citrate. Though the early characterization of these spheres indicated they might be good models for ferritin, the difficulty in obtaining reproducible samples, and the lack of structural information, has led to greater efforts being put into other approaches. 

One of these approaches is the formation of polysaccharide iron complexes (PIC), such as Niferex, a compound used in the treatment of iron deficiency anemia. PICs are formed by neutralization of FeCb-containing carbohydrate solutions with base. Mineral particles of roughly the same size as ferritin cores can be made. These contain iron in an octahedral enviromnent coordinated to oxygen. However, the long-range order of the polynuclear iron core is closer to that of akaganeite rather than ferrihydrite. ... 

Removal of Fe(lll) from storage in ferritin cores may require reduction to Fe(ll) again, possibly by ascorbic acid or glutathione. Some bacterial ferritins contain a bound cytochrome b which may assist in reduction. " 57a Released iron in the Fe " state can be incorporated into iron-containing proteins or into heme. The enzyme ferrochelatase " " catalyzes the transfer of free Fe + info protoporphyrin IX (Section 3) to form protoheme (Fig. 16-5). Iron in the Fe(II) state may also be oxidized to Fe + through action of the copper-containing ceruloplasmin (Section D) and be incorporated into heme by direct transfer from ferritin. ... 

The structure of ferritin cores has been studied by X-ray diffraction (47), electron diffraction (48), and high-resolution electron microscopy (49,50). The results indicate that the iron-containing cores of mammalian ferritins are crystalline with a unit cell based on a four-layer... 

As we stress in the following section, Fe + does not simply exit from the core of ferritin. Watt et al. (144) have completely reduced the core of horse ferritin and shown that it has a pH-dependent redox potential corresponding to 2H+ taken up by the core for each Fe + reduced to Fe ". In this study, anaerobic gel-filtration columns were used to separate reduced and partially reduced ferritin from contaminating small ions, and Mossbauer spectroscopy was employed to determine the extent of core reduction. Very little of the core iron was lost during the preparation, consistent with the low yields of Prussian blue formed by the addition of [FefCNle] to reduced ferritin (73, 146). Partially reduced ferritin cores have Mossbauer spectra indicative (50) of an iron... 

Cowley JM, Janney DE, Gerkin RC, Birseck PR (2000) The stractrrre of ferritin cores determined by electron rranodiffractiorr, J Stractrtral Biol 131 210-216 CRC Book. CRC Handbook of Chemistry and Physics 1985-1986 6thEditiorr, Eds. R.C. Weast, M.J. Astle, and W.H. Beyer. CRC Press, Boca Ratorr, Florida... 

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