Besides the selenocysteine-containing selenoproteins, there are also some selenoproteins known from bacterial species, which have selenium bound non-covalently. Most of these proteins are thought to contain a selenide-ligand to a molybdopterin cofactor at their active sites (e. g. nicotinate dehydrogenase of Eubacterium barkeri, or xanthine dehydrogenases). Selenium is also specifically incorporated into modified bases of some tRNAs (as 2-seleno-5-methylaminomethyl-uridine).
In addition, selenium occurs in proteins as unspecifically incorporated selenomethionine, which replaces methionine residues. Proteins containing such unspecifically incorporated selenomethionine residues are not regarded as selenoproteins. However, replacement of all methionines by selenomethionines is a widely used recent technique in solving the phase problem during X-ray crystallographic structure determination of many proteins (MAD-phasing). While the exchange of methionines by selenomethionines appears to be tolerated (at least in bacterial cells), unspecific incorporation of selenocysteine in lieu of cysteine seems to be highly toxic. This may be one reason for the existence of a rather complicated pathway of selenocysteine biosynthesis and specific incorporation into selenoproteins, which avoids the occurrence of the free amino acid as intermediate. Thus, even if a selenocysteine-containing selenoprotein is taken up in the diet and used as selenium-source, the amino acid has to be degraded prior to synthesising a new selenocysteine for incorporation into a selenoprotein.
Selenium is a vital nutrient in animals and humans. About 25 different selenocysteine-containing selenoproteins have so far been observed in human cells and tissues. Since lack of selenium deprives the cell's ability to synthesize selenoproteins, many health effects of low selenium intake are believed to be caused by the lack of on or more specific selenoproteins. In fact, 3 selenoproteins, TR1, TR3 and GPx4, have been shown to be essential in mice knockout experiments. On the other side, too much selenium in the diet causes toxic effects and leads to selenium poisoning. The threshold between essential and toxic concentrations of this element is rather narrow (the factor is in the range of 10-100).
References
- G. V. Kryukov, S. Castellano, S. V. Novoselov, A. V. Lobanov, O. Zehtab, R. Guigó, and V. N. Gladyshev (2003). "Characterization of mammalian selenoproteomes". Science 300 (5624): 1439–1443.
- Gregory V. Kryukov and Vadim N. Gladyshev (2004). "The prokaryotic selenoproteome". EMBO Rep 5 (5): 538–543.
- Matilde Maiorino, Valentina Boselloa, Fulvio Ursinia, Carlo Forestab, Andrea Garollab, Margherita Scapina, Helena Sztajerc, and Leopold Flohéc (2003). "Genetic variations of gpx-4 and male infertility in humans". Biol Reprod 68 (4): 1134–1141.
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