Study on Detoxification and Utilization of Selenomethionine::A Role of Cystathionine γ-lyase in Selenomethionine Metabolism
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Selenium (Se) is an essential trace element and toxicant for mammals. In human, Se is supplied by various kinds of food. Selenomethionine (SeMet), the Se analog of methionine (Met), is the major chemical form in plants. SeMet could be metabolized by the same reactions as the metabolic reactions of Met: it is activated initially by adenosylation, demethylated, and finally converted to selenocysteine (SeCyH) via selenohomocysteine and selenocystathionine. SeCyH formed could be degraded further by selenocysteine β-lyase to hydrogen selenide (H2Se) and might then be incorporated into functional selenoproteins as SeCyH residues via gene products though selenocysteinyl-tRNA. H2Se is classified as a more toxic compound than other Se compounds, so an excess amount of it is immediately transformed to methylated Se compounds as detoxicant. 1β-Methylseleno-N-acetyl-D-galactosamine is excreted as the major form into urine at nutritional dose. Meanwhile, trimethylselenonium ion (TMSe) is known to be excreted into urine at high-toxic doses. Our recent work indicates that SeMet is enzymatically converted to methylselenol (MMSe), α-ketobutyrate, and ammonia by mouse hepatic enzyme. We termed the novel enzyme SeMet α, γ-elimination enzyme and purified it to homogeneity for the first time. The target enzyme was proved to be cystathionine γ-lyase by the MS analytical techniques, both the peptide mass fingerprinting search and peptide sequence tags search. The metabolic pathway that directly transforms SeMet to MMSe is more effective in the detoxification when SeMet is administered at toxic dose, because H2Se produced in the metabolism from SeMet via SeCyH inhibits the methylation metabolism and enhances the toxicity. Furthermore, MMSe generated from SeMet by cystathionine γ-lyase is utilized for glutathione peroxidase biosynthesis. Cystathionine γ-lyase, which plays an important role in not only the Se detoxification but also the selenoproteins biosynthesis, is a notable enzyme in SeMet metabolism.
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