論文 - 詳細
| RRC ID | 77501 |
|---|---|
| 著者 | Hayakawa T, Kobayashi Y, Cui X, Hirano S. |
| タイトル | A new metabolic pathway of arsenite: arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19. |
| ジャーナル | Arch Toxicol |
| Abstract |
The metabolism of arsenic is generally accepted to proceed by repetitive reduction and oxidative methylation; the latter is mediated by arsenic methyltransferase (Cyt19). In human urine, the major metabolites of inorganic arsenicals such as arsenite (iAsIII) and arsenate (iAsV) are monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)). On the other hand, in rat bile, the major metabolites of iAsIII have been reported to be arsenic-glutathione (As-GSH) complexes. In the present study we investigate whether these As-GSH complexes are substrates for arsenic methyltransferase by using human recombinant Cyt19. Analyses by high-performance liquid chromatography-inductively coupled plasma mass spectrometry suggested that arsenic triglutathione (ATG) was generated nonenzymatically from iAsIII when GSH was present at concentrations 2 mM or higher. Human recombinant Cyt19 catalyzed transfer of a methyl group from S-adenosyl-L-methionine to arsenic and produced monomethyl and dimethyl arsenicals. The methylation of arsenic was catalyzed by Cyt19 only when ATG was present in the reaction mixture. Moreover, monomethylarsonic diglutathione (MADG) was a substrate of Cyt19 for further methylation to dimethylarsinic glutathione (DMAG). On the other hand, monomethylarsonous acid (MMA(III)), a hydrolysis product of MADG, was not methylated to dimethyl arsenical by Cyt19. These results suggest that As-GSH complexes such as ATG and MADG were converted by Cyt19 to MADG and DMAG, respectively. Both MADG and DMAG were unstable in solution when the GSH concentration was lower than 1 mM, and were hydrolyzed and oxidized to MMA(V) and DMA(V), respectively. Metabolism of iAsIII to methylated arsenicals by Cyt19 was via ATG and MADG rather than by oxidative methylation of iAsIII and MMA(III). |
| 巻・号 | 79(4) |
| ページ | 183-91 |
| 公開日 | 2005-4-1 |
| DOI | 10.1007/s00204-004-0620-x |
| PMID | 15526190 |
| MeSH | Animals Arsenic / metabolism* Arsenites / metabolism* Chromatography, High Pressure Liquid Chromatography, Ion Exchange Cytosol / enzymology Cytosol / metabolism Glutathione / metabolism* Humans Hydrogen Peroxide / pharmacology In Vitro Techniques Liver / enzymology Liver / metabolism Male Mass Spectrometry Methylation Methyltransferases / metabolism* Rats Rats, Sprague-Dawley Recombinant Proteins / metabolism |
| IF | 5.059 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Policy sources |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 |