Ferroxidase

Another condition involving ceruloplasmin is aceru-loplasminemia. in this genetic disorder, levels of ceruloplasmin are very low and consequently its ferroxidase activity is markedly deficient. This leads to failure of release of iron from cells, and iron accumulates in certain brain cells, hepatocytes, and pancreatic islet cells. Affected individuals show severe neurologic signs and have diabetes mellitus. Use of a chelating agent or administration of plasma or ceruloplasmin concentrate may be beneficial. 

Blake, D.R., Blann( A., Bacon, P.A., Farr, M., Gutteridge, J.M.C. and Halliwell, B. (1983). Ferroxidase and ascorbate oxidase activities in synovial fluid from rheumatoid joints. Clin. Sci. 64, 551-553. 

Ferritin, bacterioferritin Vertebrates, bacteria Ferroxidase ( ) EX34EX2HX4lEX36E ... 

Although channel mutations and chemical modifications reduce rates of iron oxidation and uptake, they do not completely abolish the ferroxidase activity of... 

The stoichiometries of both oxygen consumption and of proton release subsequent to Fe(III) hydrolysis have been determined by using a combined oximeter and pH stat (Yang et ah, 1998). The overall reaction at the ferroxidase centre is postulated to be ... 

The initial stages of iron incorporation requires the ferroxidase sites of the protein. Thereafter the inner surface of the protein shell provides a surface which supplies ligands that can partially coordinate iron but which leave some coordination spheres available for mineral phase anions, thereby enabling the biomineralization process to proceed, with formation of one or more polynuclear ferrihydrite crystallites. Iron is transferred from the ferroxidase sites to the core nucleation sites by the net reaction (Yang et ah, 1998) ... 

It has been proposed that Glu-61 could alternately act as a ligand to the ferroxidase site and to the nucleation site, and hence serve as a go-between to move iron (eventually in both directions) from one site to another (Lawson et al, 1991). What is clear is that modification of both the ferroxidase centre and the nucleation centre leads to ferritins which do not oxidize or incorporate iron (Wade et al, 1991 Sun et al, 1993). 

Hence, the overall reaction for iron oxidation and hydrolysis at the ferroxidase centre, followed by further hydrolysis and migration to the core nucleation sites (equation 7) is ... 

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... 

It is unfortunately the case that when we incubate apoferritin with a certain number of iron atoms (for example as ferrous ammonium sulfate), the product, after elimination of non-protein-bound iron, does not have a homogeneous distribution of iron molecules which were able to (i) take up iron rapidly through the three fold channels, (ii) quickly transfer it and form a diiron centre on a ferroxidase site, and (iii) to transfer the iron inward to a nucleation site, where (iv) it will begin to catalyse iron oxidation on the surface of the growing crystallite, will accumulate iron much more rapidly, and in much greater amounts than molecules in which steps (i), (ii) and (iii) are slower, for whatever reasons (perhaps most importantly subunit composition, and the disposition of subunits of the two types H and L, one with regard to the other). This polydispersity makes the analysis of the process of iron uptake extremely difficult. 

Haephaestin (Vulpe et al., 1999) basolateral membrane ferroxidase activity Vulpe et al, 1999) sex-linked anemia transfer... 

Ceruloplasmin Ferroxidase activity Cp-/- mice (Harris et al, 1999) Aceruloplasminaemia (Logan et al, 1994 Takahashi et al, 1996) deficient iron mobilization low serum iron tissue iron overload... 

Tatur, J. and Hagen, W.R. 2005. The dinuclear iron-oxo ferroxidase center of Pyrococcus furiosus ferritin is a stable prosthetic group with unexpectedly high reduction potentials. FEBS Letters 579 4729 1732. 

The mammalian protein has an enzymatic activity and catalyzes the oxidation of Fe2+ at ferroxidase sites present only in H subunits [88], This reaction may proceed through a di-ferric-p-peroxo species, which rapidly decomposes, eventually forming a ferric oxyhydroxide mineral core via an inorganic hydrolysis polymerization [89]. 

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