Studies on in vitro S-methylation of naturally occurring thiol compounds with N-methyl-N-nitrosourea and methyl methanesulfonate.
N-Methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS) were found to rapidly methylate glutathione (GSH) in vitro yielding S-methyl glutathione, as verified and quantitated by high-performance liquid chromatography and thin-layer chromatography. Formation of S-methylcysteine in the acid-hydrolyzate of the methylated GSH further confirmed the formation of S-methyl glutathione. Other naturally occurring thiol compounds such as cysteine and homocysteine were also methylated by MNU. The observed pH dependency of GSH methylation by MNU suggests that the sulfide anion form of the thiol may represent the favored methyl acceptor. The high reactivity of GSH toward MNU and MMS may be of biological significance in that it could compete with macromolecular cellular components as a target for alkylation.
D000596:Amino Acids; D005978:Glutathione / Q000031:analogs & derivatives; D007700:Kinetics; D008741:Methyl Methanesulfonate; D008745:Methylation; D008770:Methylnitrosourea; D010084:Oxidation-Reduction
D000596:Amino Acids; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate; D005978:Glutathione; C017514:S-methyl glutathione