LC-ICP-MS and LC-ESI-(MS)n identification of Se-methylselenocysteine and selenomethionine as metabolites of methylseleninic acid in rat hepatocytes

Gabel-Jensen, Charlotte; Odgaard, Jacob; Skonberg, Christian; Badolo, Lassina; Gammelgaard, Bente

doi:10.1039/b807805j

Cited by 22 publications

(26 citation statements)

References 31 publications

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“…The same group identified S-(methylseleno)cysteine in intestinal epithelial cell homogenates by LC-ICP-MS and LC-ESI-MS after incubation with methyl seleninic acid and showed that its formation did not require the presence of an enzymatic system but only cysteine [67]. They further identified Se-(methyl)selenocysteine and selenomethionine as metabolites of methylseleninic acid in rat hepatocytes and showed that S-(methylseleno)cysteine and S-(methylseleno)glutathione were intermediates in their formation [68].…”

Section: Resultsmentioning

confidence: 99%

Speciation of selenium dietary supplements; formation of S-(methylseleno)cysteine and other selenium compounds

Amoako

Uden

Tyson

2009

Analytica Chimica Acta

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a b s t r a c tSpeciation of selenium is of interest because it is both essential and toxic to humans, depending on the species and the amount ingested. Following indications that selenium supplementation could reduce the incidence of some cancers, selenium-enriched yeast and other materials have been commercialized as supplements. Most dramatically however, the SELECT trial that utilized l-selenomethionine as the active supplement was terminated in 2008 and there is much debate regarding both the planning and the results of efficacy studies. Further, since dietary supplements are not regulated as pharmaceuticals, there are concerns about the quality, storage conditions, stability and selenium content in selenium supplements. Enzymatic hydrolysis enabled selenium speciation profiles to be obtained by high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and following derivatization gas chromatography with atomic emission detection (GC-AED). Coated fiber solid phase microextraction (SPME) was used to extract volatile selenium species for determination by GC-AED and GC-MS. Similar speciation patterns were observed between yeast-based supplements subject to extended storage and those heated briefly at elevated temperatures. All the yeast-based supplements and one yeast-free supplement formed S-(methylseleno)cysteine on heating. Evidence was obtained in support of the hypotheses that S-(methylseleno)cysteine is formed from a reaction between dimethyldiselenide and cysteine or cystine.

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Section: Resultsmentioning

confidence: 99%

Speciation of selenium dietary supplements; formation of S-(methylseleno)cysteine and other selenium compounds

Amoako

Uden

Tyson

2009

Analytica Chimica Acta

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“…The limit of detection and limit of quantification were 1.2 and 4.1 nM, respectively. The accuracy of the method has previously been verified by analysis of a certified serum control (Seronorm level 1, SERO AS, Billingstad, Norway) [23].…”

Section: Total Selenium Determination By Flow Injection Analysismentioning

confidence: 99%

Estimating Intestinal Absorption of Inorganic and Organic Selenium Compounds by in Vitro Flux and Biotransformation Studies in Caco-2 Cells and ICP-MS Detection

Gammelgaard

Rasmussen

Gabel-Jensen

et al. 2011

Biol Trace Elem Res

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The aim of the present work was to compare and estimate absorption and biotransformation of selected selenium compounds by studying their fluxes across Caco-2 cells. Five different selenium compounds, selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenate, selenite, and methylseleninic acid (MeSeA), were applied to Caco-2 cells in a concentration of 10 μM, and fluxes in both directions were studied for 2 h. Fluxes of selenite and MeSeA in the presence of excess reduced glutathione (selenite + GSH and MeSeA + GSH) and flux of MeSeA in the presence of excess cysteine (MeSeA + Cys) were also studied. Selenium absorptive and exsorptive fluxes and accumulation in cell cytosol were analyzed by means of flow injection inductively coupled plasma mass spectrometry (ICP-MS). Absorptive flux of SeMet, MeSeCys, and selenate showed values correlating to complete in vivo absorption, while selenite and MeSeA fluxes correlated to poor in vivo absorption. Speciation analysis of cell lysate and donor and receptor solutions by LC-ICP-MS showed limited transformation of all selenium compounds. Extensive transformation as well as significantly increased absorptive flux was observed when co-administering selenite with glutathione compared to administering selenite alone. These observations are possibly due to formation of selenodiglutathione (GS-Se-SG) which may be absorbed differently than selenite. Concomitant application of GSH or cysteine with MeSeA resulted in extensive transformation of MeSeA, including volatile species, whereas no significant increases in fluxes were observed. In summary, the absorption of selenite selenate and the selenoamino acids is considered complete under physiological conditions, but the absorption mechanisms and metabolism of the compounds are different.

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“…It is conceivable that this enzyme has low homoserine sulfhydrylase activity, which would directly generate SeMet from MeSeH. The identification of SeMet in MSeA-treated human lymphoma cells suggests that such a pathway might be relevant in mammalian cells, which cannot synthetize amino acids from inorganic sulfur [ 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae

Dauplais

Bierła

Maizeray

et al. 2021

IJMS

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Methylselenol (MeSeH) has been suggested to be a critical metabolite for anticancer activity of selenium, although the mechanisms underlying its activity remain to be fully established. The aim of this study was to identify metabolic pathways of MeSeH in Saccharomyces cerevisiae to decipher the mechanism of its toxicity. We first investigated in vitro the formation of MeSeH from methylseleninic acid (MSeA) or dimethyldiselenide. Determination of the equilibrium and rate constants of the reactions between glutathione (GSH) and these MeSeH precursors indicates that in the conditions that prevail in vivo, GSH can reduce the major part of MSeA or dimethyldiselenide into MeSeH. MeSeH can also be enzymatically produced by glutathione reductase or thioredoxin/thioredoxin reductase. Studies on the toxicity of MeSeH precursors (MSeA, dimethyldiselenide or a mixture of MSeA and GSH) in S. cerevisiae revealed that cytotoxicity and selenomethionine content were severely reduced in a met17 mutant devoid of O-acetylhomoserine sulfhydrylase. This suggests conversion of MeSeH into selenomethionine by this enzyme. Protein aggregation was observed in wild-type but not in met17 cells. Altogether, our findings support the view that MeSeH is toxic in S. cerevisiae because it is metabolized into selenomethionine which, in turn, induces toxic protein aggregation.

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LC-ICP-MS and LC-ESI-(MS)n identification of Se-methylselenocysteine and selenomethionine as metabolites of methylseleninic acid in rat hepatocytes

Cited by 22 publications

References 31 publications

Speciation of selenium dietary supplements; formation of S-(methylseleno)cysteine and other selenium compounds

Speciation of selenium dietary supplements; formation of S-(methylseleno)cysteine and other selenium compounds

Estimating Intestinal Absorption of Inorganic and Organic Selenium Compounds by in Vitro Flux and Biotransformation Studies in Caco-2 Cells and ICP-MS Detection

Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae

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