Toxicity of Dimethyl Selenide in the Rat and Mouse

McConnell, Kenneth P.; Portman, Oscar W.

doi:10.3181/00379727-79-19333

Cited by 105 publications

(56 citation statements)

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“…However, excessive selenium is excreted not only into urine but also into breath (exhaled into breath). [30][31][32] In either case, selenium is excreted after being methylated stepwise. Urinary metabolites are known to be monomethylated selenium and trimethylselenonium (TMSe), while selenium is exhaled in the form of dimethylselenide.…”

Section: Excretion Of Seleniummentioning

confidence: 99%

Metabolomics of Selenium: Se Metabolites Based on Speciation Studies

Suzuki

2005

JOURNAL OF HEALTH SCIENCE

217

191

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Selenium is a trace element essential for the normal function of the body. This metalloid is quite unique in its metabolism compared with typical essential metals such as copper and zinc. In the present communication, the metabolism of selenium in the body was reviewed from the viewpoint of metabolomics based on speciation studies. Both inorganic and organic forms of slenium can be the nutritional source, and they are transformed to the common intermediate, selenide or its equivalent. Selenite and selenate are reduced simply to selenide for further utilization and/or excretion. On the other hand, organic selenocysteine is directly lysed to selenide, while selenomethionine is transformed to selenocysteine (trans-selenation pathway), similarly to the trans-sulfuration pathway for methionine to cysteine, and then lysed to selenide. Selenide is known to be transformed to selenocysteine on tRNA, and the selenocysteinyl residue is incorporated into selenoprotein sequences by the codon specific to selenocysteine, UGA. Diverse selenium chemicals in foods seem to be recognized as selenium species and transformed to selenide, and then utilized for the synthesis of selenoproteins. Surplus selenium is methylated stepwise to methylated selenium metabolites from the common intermediate selenide. The major urinary metabolite is 1β-methylseleno-N-acetyl-Dgalactosamine (selenosugar). Trimethylselenonium has been recognized as the urinary metabolite excreted in response to excessive doses and as a biological marker for excessive doses. However, recent results contradicted this.

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Section: Excretion Of Seleniummentioning

confidence: 99%

Metabolomics of Selenium: Se Metabolites Based on Speciation Studies

Suzuki

2005

JOURNAL OF HEALTH SCIENCE

217

191

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“…This enzyme could become a key in the remediation of anthropogenically or naturally Se-contaminated sites. DMSe is 500 to 700 times less toxic than inorganic selenium species (6,8,12). This process is also likely to be involved in the production of dimethyl selenide in eukaryotes, including humans, because of the widely conserved nature of the methyltransferase involved (2).…”

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confidence: 99%

Methylation of Inorganic and Organic Selenium by the Bacterial Thiopurine Methyltransferase

et al. 2002

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Escherichia coli cells expressing the tpm gene encoding the bacterial thiopurine methyltransferase (bTPMT) are shown to methylate selenite and (methyl)selenocysteine into dimethylselenide (DMSe) and dimethyldiselenide (DMDSe). E. coli cells expressing tpm from a gene library cosmid clone (harboring a Pseudomonas syringae insert of about 20 kb) also methylated selenate into DMSe and DMDSe. bTPMT is the first methyltransferase shown to be involved in the methylation of these selenium derivatives.Selenium is an essential element, but its presence in micromolar concentrations can lead to death and deformities of wildlife (14). It can be found in enzymes under the form of selenocysteine amino acids or bound in such a way that it can be detached by denaturing or reducing agents (for a review, see reference 9). Bacteria have been shown to play a key role in the biological cycle of selenium by reduction (19) and volatilization of inorganic selenium (for a review, see references 4 and 7) in the environment. A significant contribution to the understanding of the biochemistry of this cycle was made by studies with Thauera selenatis. A dissimilatory selenate reductase enzyme complex was found in this bacterium and shown to be trimeric and periplasmic and to reduce selenate to selenite (18). This selenate reductase was shown to have a high affinity and turnover rate for selenate, much higher than the ones of the bacterial periplasmic nitrate reductases (17). The T. selenatis nitrite respiratory system was shown to reduce selenite to elemental selenium in the presence of nitrate (3). T. selenatis was isolated from sediments of the San Joaquin Valley, and its selenate-reducing capacity was recently used for the bioremediation of selenium from agricultural drainage water (1). The biochemistry and genetics of the enzymes involved in selenium methylation remain almost unexplored. Bioremediation by volatilization of selenium from contaminated sites represents an interesting alternative to the use of selenate-respiring bacteria (10).Recently, we discovered a methyltransferase that might be involved in the methylation of inorganic selenite (2). This enzyme, named the bacterial thiopurine methyltransferase (bTPMT), was shown to catalyze the S adenosylmethylation of aromatic and heterocyclic sulfhydryl compounds like 6-mercaptopurine. It belongs to a group of methyltransferases whose presence in eukaryotes (human, rat, mouse, etc.) is very well documented (for examples, see references 15 and 20). The human TPMT (hTPMT) is essential for the metabolism of thiopurine drugs (11), which are frequently used in the treatment of human autoimmune diseases and for transplantations (5, 16). The bTPMT, overexpressed in Escherichia coli, conferred resistance to tellurite and the ability to grow at high concentrations of sodium biselenite (2). Here, we present clear evidence that bTPMT is involved in the methylation of inorganic and organic selenium into dimethylselenide (DMSe) and dimethyldiselenide (DMDSe). bTPMT is the first methyltransferase sh...

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“…Shrift, 1973). The ability of various forms of inorganic selenium to be metabolized to reduced organic forms has been shown in animals (McConnell & Portman, 1952), bacteria (Tuve & Williams, 1961) and plants (Fleming & Alexander, 1972). Whether the enzymes of the sulphur-assimilatory system are responsible for these biological transformations is not known.…”

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confidence: 99%

Activation of selenate by adenosine 5′-triphosphate sulphurylase from Saccharomyces cerevisiae

Dilworth¹,

Bandurski²

1977

Biochemical Journal

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In the presence of ATP and Mg2+, ATP sulphurylase from Saccharomyces cerevisiae catalysed the conversion of selenate into a compound with the electrophoretic and acid-lability properties of adenosine 5'-sulphatophosphate. Structural characterization, involving extensive purification of adenosine 5'-selenophosphate, proved impossible. However, we showed ATP-, Mg2+-and ATP sulphurylase-dependent, and inorganic pyrophosphatase-stimulated, production of elemental selenium from selenate in the presence of GSH (reduced glutathione). Since selenate was not reduced by GSH, this reaction proved that ATP sulphurylase had formed an active selenate. The enzymecatalysed formation of elemental selenium had the same kinetics and GSH-dependency as the non-enzymic reduction ofselenite to elemental selenium by GSH. In the presence of inorganic pyrophosphatase, 2mol of Pi was released for each mol of 'active selenate' formed. This was shown by a spectrophotometric assay for elemental selenium. The observed reactivity with thiols and the instability of the enzymic product were those predicted for selenium anhydrides. By analogy with the chemistry of sulphur, the product of the thiolytic cleavage of a selenium anhydride would be converted into selenite. The selenite would then be reduced by the thiol to elemental selenium. We conclude that ATP sulphurylase can catalyse the formation of adenosine 5'-selenophosphate. The anhydride can be reduced by thiols in a manner similar to the reduction of selenite. These results probably explain the ability of mammals, lacking a sulphate reductase system, to incorporate selenium from selenate into seleno-amino acids.

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Toxicity of Dimethyl Selenide in the Rat and Mouse

Cited by 105 publications

References 0 publications

Metabolomics of Selenium: Se Metabolites Based on Speciation Studies

Metabolomics of Selenium: Se Metabolites Based on Speciation Studies

Methylation of Inorganic and Organic Selenium by the Bacterial Thiopurine Methyltransferase

Activation of selenate by adenosine 5′-triphosphate sulphurylase from Saccharomyces cerevisiae

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