Multicopper oxidase eukaryotic

Osaki, 1974 Osaki, 1966 Osaki et al., 1966). Using the kinetic values given above, they estimated that without the ferroxidase activity of Cp in the plasma 80% of the iron released from erythrocyte turnover would accumulate as non-Tf-bound Fe(ll) and thereby would be unavailable for reabsorption by the reticuloendothelial system. Furthermore, this free Fe(II) could catalyze the formation of reactive oxygen species via the Fenton reaction. This, in turn, could lead to a subsequent organismal pathophysiology (Miyajima et al., 1996 Nakano, 1993). This inference has been strikingly confirmed by research over the past 6 years in both yeasts and mammals this research has directly tested the hypothesis that multicopper oxidase-dependent ferroxidase activity is essential to eukaryotic iron homeostasis (Askwith et al., 1996 Harris et al., 1995 1998 Wessling-Resnick, 1999). 

Based on present sequence data, known or likely ferroxidase enzymes can be identihed in several eukaryotes. These enzymes are listed in Table 11. All are multicopper oxidases, by sequence homology at least. In mammals, they include ceruloplasmin and, most likely, hephaestin (Hp), although only mouse Hp (mHp) has been characterized at this time (Vulpe et al., 1999). The alignments in Fig. 5A show that mHp is essentially... 

FET3 gene product of S. cerevisiae is a multicopper oxidase and plays a key role in iron metabolism of this eukaryote has underpinned the function of ceruloplasmin in vertebrate iron transport. By virtue of its ferroxidase activity, ceruloplasmin converts Fe(II) into Fe(III), which binds to the iron-binding protein transferrin. Ceruloplasmin is critical for iron egress from some cell types. The transport system responsible for iron release into plasma has not been identified. ... 

The accumulation of iron is dependent on its transport into the cell. Askwith and Kaplan (Chapter 4) discuss iron transport mechanisms in eukaryotic cells, developing models based on studies carried out in the yeast, Saccharomyces cerevisiae. These cells possess both siderophore-dependent and elemental iron transport systems. The latter system relies on cell surface ferrireductases to convert extracellular ferric chelates to ferrous iron, which can be transported through either a high or low affinity iron transport system. Studies on a high affinity ferrous iron transporter (FET3) revealed that the multicopper oxidase will oxidize ferrous to ferric iron, which is then mobilized across the membrane by a ferric transmembrane permease (Ftrlp). This is a highly specific transport system in yeast it only transports iron. In humans, the copper enzyme, ceruloplasmin, is responsible for the radical-free oxidase activity. This plasma protein oxidizes the ferrous iron that is excreted from cells into the transferrin-usable ferric form. 

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