Sequential methylation of 2-mercaptoethanol to the dimethyl sulfonium ion, 2-(dimethylthio)ethanol, in vivo and in vitro.
Thioether methyltransferase (S-adenosyl-L-methionine: thioether S-methyltransferase; EC 2.1.1.96) catalyzes the methylation of X in compounds of the type R-X-R'(X = S, Se, Te), yielding a methyl onium ion. Previous results using mice have demonstrated a role for thioether methyltransferase in the conversion and clearance of thioethers by methylation to more water-soluble methyl sulfonium ions suitable for excretion in the urine. A potential major physiological source of thiethers is reactions catalyzed by microsomal thiol methyltransferase (S-adenosyl-L-methionine: thiol S-methyltransferase; EC 2.1.1.9), which has been shown to methylate a diverse range of aliphatic sulfhydryl compounds. This study provides evidence for the sequential methylation of the aliphatic thiol, 2-mercaptoethanol, first to the methyl thioether, 2-(methylthio)ethanol, by thiol methyltransferase followed by methylation of this methyl thioeter to the dimethyl sulfonium ion, 2-(-dimethylthio)ethanol, by thioether methyltransferase. This sequence of reactions was demonstrated in vivo by injecting mice i.p. with radioactive 2-mercaptoethanol and analyzing the labeled methylated products, 2-(methylthio)ethanol and 2(dimethylthio)ethanol, in the urine by HPLC. In addition, the system converting 2-mercaptoethanol to 2-(dimethylthio)ethanol was reconstituted in vitro using solubilized mouse liver microsomes as a source of thiol methyltransferase and purified thioether methyltransferase from mouse lung. The results of these in vivo and in vitro studies established the sequential methylation of 2-mercaptoethanol by these two enzymes.
Carrithers
S L
SL
Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
Hoffman
J L
JL
D000818:Animals; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008623:Mercaptoethanol / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice
D008623:Mercaptoethanol; C009352:sulfocholine; D008780:Methyltransferases; C055340:S-adenosyl methionine thioether S-methyltransferase; C022742:thiol S-methyltransferase; D002794:Choline