Selenium proteins, incorporation into

Selenocysteine was identified in 1976 (57) in a protein produced by Clostridium stricklandii, and it is thought to be the form in which selenium is incorporated, stoichiometricaHy, into proteins. Studies with rats show that over 80% of the dietary selenium given them is incorporated into proteins, thus selenocysteine takes on metaboHc importance. Selenoproteins having known enzymatic activities contain selenocysteine at the active sites. Two other forms of metabohc selenium are recognized methylated selenium compounds are synthesized for excretion, and selenium is incorporated into some transfer ribonucleic acids (tRNAs) in cultured cells (58). Some of the more important seleno-compounds are Hsted in Table 4. Examples of simple ring compounds are shown in Eigure 4. 

The trace element selenium plays an essential role in the activity of some bacterial and eukaryotic antioxidant enzymes (34). Selenium is incorporated into proteins in the form of the so-called twenty-first amino acid selenocysteine, which is encoded by a UGA stop codon. Although the chemical structure of selenocysteine differs from cysteine only by the replacement of the sulfur atom with selenium, the lower pKa of selenocysteine (5.2) allows for ionization of selenocysteine at physiological pH (35). To read through the UGA stop codon selectively, selenocysteine insertion requires a variety of proteins and RNA stmctures. 

Selenium is incorporated into Se-requiring enzymes by the modification of serine. This serine is not modified when it is in the free state or when it occurs in a polypeptide chain. The serine residue in question is modified when it occurs boimd to transfer RNA, that is, eis the aminoacyl-tRNA derivative. Seryl-tRNA is converted to selenocysteinyl-tRNAby the action of selenocysteine synthase (Stur-chler et al, 1993). The codon for selenocysteine is UGA (TGA in DNA UGA in mRNA). The fact that this particular triplet of bases codes for an amino acid is very imusual, as UGA normally is a stop codon. Stop codons occur in mRNA and signal the termination of synthesis of the protein however, in the case of the UGA codons that code for selenocysteine residues, regions of the mRNA that lie beyond the coding sequence somehow convert the UGA from a codon that halts translation to one that codes for selenocysteine (Figure 10.55). The structure of selenocysteine is shown in Figure 10.56. 

One biological function for selenium is incorporation into the amino acid selenocysteine that is found in some proteins [174]. Microbial dissimilatory reduction of selenate to selenite and then to elemental... 

Bakers inactive dry yeast is also widely used in the food industry. This yeast may be grown specifically as a food supplement and consequently there is a choice in its composition by varying growth conditions and feedstock makeup. It can possibly produce high levels of nicotinic acid and thiamin, the cmde protein content can be raised to 50—55% and it can be used as a vehicle for the incorporation of micronutrients such as selenium or chromium into the diet. 

The importance of the selenium-analog of cysteine, selenocysteine (Se-cysteine), HSeCH2CHNH2COOH, and its incorporation into protein via a ribosomal mechanism has earned it the label of the 21st amino acid.112 115 Assuming L configuration at the a carbon, Se-cysteine is represented by 49, R=H (Scheme 17). 

Figure 1 Overview of specific use of seienium in bioiogical systems. Selenium can be incorporated into macromolecules in at least three separate pathways. From the reduced form of selenide, selenium is activated to selenophosphate by the action of the enzyme selenophosphate synthetase (SPS or SelD). This activated form is then used as a substrate for pathway-specific enzymes that lead to (1) insertion as selenocysteine into proteins during translation (selenoproteins), (2) incorporation into tRNA molecules as mnm Se U or Se U, and (3) insertion into a unique class of molybdoenzymes as a labile, but required, cofactor. The need for activation to selenophosphate has been demonstrated in all cases at the genetic and biochemical level, with the exception of the labile selenoenzymes, where activation of selenium has only been proposed based on proximity of genes within an operon encoding SPS and a molybdoenzyme. ...

Selenium is present in meat, seafood and cereals. The former two contain the highest levels. It is present in soil as inorganic selenium that enters the food chain via plants. In plant protein, it is present as selenomethionine and in animals as selenocysteine this difference is due to the metabolism of selenomethionine in the liver as part of the normal catabolic pathway for methionine (Chapter 8). Somewhat surprisingly, selenocysteine is incorporated into protein via a specific tRNA which possesses a UCA anticodon for this amino acid. 

The unusual amino acid selenocysteine (a derivative of cysteine in which the sulfur atom is replaced by a selenium atom) is an essential component in a small number of proteins. These proteins occur in prokaryotes and eukaryotes ranging from E. coli to humans. In all cases, selenocysteine is incorporated into protein during translation in response to the codon UGA. This codon usually serves as a termination codon but occasionally, in some required but unknown context of bases, is used to specify selenocysteine instead. 

Although known for its toxicity, but unlike antimony and arsenic, selenium is an essential element which has been identified as part of several prokaryotic and eukaryotic proteins in the form of the amino acid, selenocysteine. Selenocysteine has been referred to as the 21st amino acid since gene products required for its incorporation into protein were discovered in bacteria (Stadtman, 1996). Aspects of the mechanism of selenocysteine insertion during protein synthesis in eukaryotes are currently being investigated (Low and Berry, 1996). The two strands of current selenium research are... 

Mason, A.C. 1994. Selenium incorporation into selenocysteine in yeast proteins. FASEB J. 8(4), A541. 

Selenium Speciation in Edible Animal Tissues Reports on Se specia-tion analysis in edible animal tissues have been scarce. Speciation analysis of Se in cod muscle tissue was performed by separating the species using both RP- and SE-HPLC prior to ICP-MS detection. The main Se compound found in enzymatic hydrolysates was selenomethionine [42], This selenocompound was absent in MeOHDHCl extracts, indicating that Se was mainly incorporated into proteins. A number of unidentiFed Se species were also detected in cod muscle tissue, the separated Se compounds being quantised on-line by post-column isotope dilution [42], Soluble Se compounds extracted from muscles of chicken, turkey, duck, ostrich, lamb, cattle, and pig were separated by SEC with ICP-MS detection. Four peaks were observed, but distribution of Se among these peaks varied considerably in tissues from different animal species [86]. 

How have selenium-accumulators been able to absorb so much Se without any damage to themselves These plants are able to separate inorganic S (as sulphate) from inorganic Se (as selenate or selenite), when they enter in the plants, and to channel the Se into the synthesis of nonprotein amino acid analogues, which are not therefore incorporate into protein synthesis. The adapted plants then sequester them in the vacuoles of the leaves, where they are perfectly harmless to the plants but intensely harmful to any unsuspecting grazing animals. In the non-adapted plants selenium toxicity may be attributed to the replacement of cysteine by selenocysteine and the production of disfunctional proteins in which S-S bond between polypeptide chains are replaced by the more labile Se-Se bonds. Fig (14). 

Selenium is rapidly excreted in the urine some is incorporated into proteins. Elemental selenium and its oxides can be methylated. Trimethyl selenium is excreted rapidly in the urine some is exhaled. 

The concentrations of selenium in whole blood and in plasma and/or serum are related to dietary intake. About 50% to 60% of the total plasma selenium is present as the protein selenoprotein P, a highly basic protein having multiple histidine residues and about 10 atoms of selenium per molecule, Around 30% of plasma selenium is present as glutathione peroxidase (GSHPx-3) and the remainder is incorporated into albumin as selenomethionine. ... 

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