Iron core formation

Fe(III) Clusters on Ferritin Protein Coats and Other Aspects of Iron Core Formation... 

Variations in ferritin protein coats coincide with variations in iron metabolism and gene expression, suggesting an Interdependence. Iron core formation from protein coats requires Fe(Il), at least experimentally, which follows a complex path of oxidation and hydrolytic polymerization the roles of the protein and the electron acceptor are only partly understood. It is known that mononuclear and small polynuclear Fe clusters bind to the protein early in core formation. However, variability in the stoichiometry of Fe/oxidant and the apparent sequestration and stabilization of Fe(II) in the protein for long periods of time indicate a complex microenvironment maintained by the protein coats. Full understanding of the relation of the protein to core formation, particularly at intermediate stages, requires a systematic analysis using defined or engineered protein coats. 

The Iron/Proteln Interface. Interactions of Iron with the protein coat of ferritin are most easily characterized In the early stages of core formation when most. If not all, of the Iron present Is In contact with the protein coat. In the complete core, bulk Iron Is Inorganic. To date, the protein coat has been little examined early In Iron core formation except In terms of effects on the Iron environment. Studies of the Iron early In core formation will be discussed later. 

In contrast to ferritin, very little work has been done on the reconstitution of BFR cores, other than the experiments mentioned above that showed that, in the absence of phosphate, crystalline ferrihydrite formed inside the protein shell. The intermediate stages in this process are unknown, but the sigmoid iron uptake behavior (25) suggests there could be a similar succession of events oxidation and nucleation on the protein shell followed by direct oxidation on the core. The influence of the heme, if any, on BFR iron core formation also awaits investigation. As mentioned above, the presence of the iron core influences the heme redox potential, but it is not known whether the presence of heme influences the redox potential of the nonheme iron. 

Bauminger and Harrison reviewed studies of the process of iron core formation in human and horse spleen ferritins using Mossbauer spectroscopy. It was demonstrated that iron deposition within ferrihydrite core in human and horse spleen ferritin started with Fe(ll) oxidation. This process was associated with ferroxidase center of H-chains. Further, an Fe(lll) compound and Fe(lll) jL-oxo-bridged dimers in ferroxidase centers of H-chains were found, which were intermediate compounds in the process of iron oxyhydroxide core formation in horse spleen ferritin. The steps leading to ferrihydrite core formation in human L- and H-ferritins were also identified and transfer between ferritin molecules was established [M2]. 

Similarly, the oxidation of Fe " during iron core formation in recombinant human H subunit ferritin and its variants has been investigated by stopped-ftow kinetics and Mossbauer spectroscopy [494]. An intermediate species, attributed to the purple Fe -Tyr34 complex in the Fe2 site, was shown to form rapidly ( ox 1000 s ) and to decay within the first 5-10 s. This Fe -tyrosinate complex was shown to form following the rapid uptake and oxidation of Fe, and was proposed as one of the initial steps in the fast mineralization process [474]. The oxidation of Fe has been shown to lead to the formation of various species, including Fe " " monomers, dimers, and some larger clusters. Specifically, the observed fast oxida-... 

Bauminger ER, Harrison PM, Nowik I, Treffiy A. 1989. Mdssbauer spectroscopic study of the initial stages of iron core formation in horse spleen apoferritin evidence for both isolated Fe(III) atoms and oxo-bridged Fe(III) dimers as early intermediates. Biochemistry 28 5486—5493. 

Iron (II) oxidation and early intermediates of iron-core formation in recombinant human H-chain ferritin. Biochem J 296 109-719. 

Gas emission before core formation contact with metallic iron leads to a strongly reducing atmosphere containing only H2, H2O, CH4 and CO. 

Gas emission after core formation the redox state in the iron-containing minerals of the Earth s crust is determined by the ratio of Fe2+ to Fe3+. 

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... 

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). 

While core formation during hydrolysis of Fe(III) produces electrically neutral ferri-hydrite, it also produces protons two per Fe(II) oxidized and hydrolysed, whether due to iron oxidation and hydrolysis at the ferroxidase centre, followed by further hydrolysis and migration to the core nucleation sites or by direct Fe(II) oxidation and hydrolysis on the mineral surface of the growing core. These protons must either be evacuated from the cavity or else their charges must be neutralized by incoming anions, and it... 

Ferritin Structure. Ferritin is a large complex protein composed of a protein coat which surrounds a core of polynuclear hydrous ferric oxide (Fe0 0H or Fe203 nH20). Points of contact which have been observed (4) between the inner surface of the protein coat and the iron core may reflect sites of cluster formation and core nucleatlon. 

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. 

Formation of ferritin involves assemblage of the protein subunits to form the apo-ferritin shell which is then filled with the phosphated ferrihydrite core. The mechanism by which ferritin is filled and the iron core built up, has been investigated intensively in vitro. The experiments usually involved incubating apoferritin (from horse spleen) with Fe salts in the presence of an oxidant such as molecular oxygen. They showed that ferritin could be reconstituted from apoferritin and a source of Fe both the iron and the oxygen enter the protein shell, whereupon oxidation of Fe is catalysed by the interior surface of the protein shell (Macara et al., 1972). 

Figure 5-8 A Pb-Pb isochron that determined the age of the Earth to be about 4.55 Ga. Stony and iron meteorites as well as a sediment of the Earth are plotted on a Pb-Pb isochron. The sediment, as a "bulk sample of the silicate Earth in terms of Pb isotopes, plots on the same line as the meteorites, suggesting that the Earth and meteorites formed at the same time and are the same age. Erom Patterson (1956). Later studies reveal a more detailed evolution history of the Earth, including core formation (about 4.53 Ga), atmospheric formation (about 4.45 Ga), and crustal evolution.

Kleine, T., Mezger, K., Palme, H., Scherer, E. and Munker, C. (2005) Early core formation in asteroids and late accretion of chondrite parent bodies Evidence from Hf- W in CAIs, metal-rich chondrites and iron meteorites. Geochimica et Cosmochimica Acta, 69, 5805-5818. 

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