SEQUENTIAL METHYLATION OF 2-MERCAPTOETHANOL TO THE DIMETHYL SULFONIUMION, 2-(DIMETHYLTHIO)ETHANOL, IN-VIVO AND IN-VITRO

Thioether methyltransferase (S-adenosyl-L-methionine : thioether S-met hyltransferase; EC 2.1.1.96) catalyzes the methylation of X in compoun ds of the type R-X-R'(X = S, Se, Te), yielding a methyl onium ion. Pre vious results using mice have demonstrated a role for thioether methyl transferase in the conversion and clearance of thioethers by methylati on to more water-soluble methyl sulfonium ions suitable for excretion in the urine. A potential major physiological source of thioethers 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 ali phatic thiol, 2-mercaptoethanol, first to the methyl thioether, 2-(met hylthio)ethanol, by thiol methyltransferase followed by methylation of this methyl thioether to the dimethyl sulfonium ion, 2-(dimethylthio) ethanol, by thioether methyltransferase. This sequence of reactions wa s demonstrated in vivo by injecting mice i.p. with radio active a-merc aptoethanol and analyzing the labeled methylated products, 2-(methylth io)ethanol and 2(dimethylthio)ethanol, in the urine by HPLC. In additi on, the system converting 2-mercaptoethanol to 2-(dimethylthio)ethanol was reconstituted in vitro using solubilized mouse liver microsomes a s a source of thiol methyltransferase and purified thioether methyltra nsferase from mouse lung. The results of these in vivo and in vitro st udies established the sequential methylation of 2-mercaptoethanol by t hese two enzymes.