Biosynthesis and urinary excretion of methyl sulfonium derivatives of the sulfur mustard analog, 2-chloroethyl ethyl sulfide, and other thioethers
- Univ. of Louisville, KY (USA)
Thioether methyltransferase was previously shown to catalyze the S-adenosylmethionine-dependent methylation of diemthyl selenide, dimethyl telluride, and various thioethers to produce the corresponding methyl onium ions. In this paper we show that the following thioethers are also substrates for this enzyme in vitro: 2-hydroxyethyl ethyl sulfide, 2-chloroethyl ethyl sulfide, thiodiglycol, t-butyl sulfide, and isopropyl sulfide. To demonstrate thioether methylation in vivo, mice were injected with (methyl-{sup 3}H)methionine plus different thioethers, and extracts of lungs, livers, kidneys, and urine were analyzed by high-performance liquid chromatography for the presence of ({sup 3}H)methyl sulfonium ions. The following thioethers were tested, and all were found to be methylated in vivo: dimethyl sulfide, diethyl sulfide, methyl n-propyl sulfide, tetrahydrothiophene, 2-(methylthio)ethylamine, 2-hydroxyethyl ethyl sulfide, and 2-chloroethyl ethyl sulfide. This supports our hypothesis that the physiological role of thioether methyltransferase is to methylate seleno-, telluro-, and thioethers to more water-soluble onium ions suitable for urinary excretion. Conversion of the mustard gas analog, 2-chloroethyl ethyl sulfide, to the methyl sulfonium derivative represents a newly discovered mechanism for biochemical detoxification of sulfur mustards, as this conversion blocks formation of the reactive episulfonium ion that is the ultimate alkylating agent for this class of compounds.
- OSTI ID:
- 5707504
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (USA), Vol. 4:15; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
METHYL TRANSFERASES
BIOCHEMICAL REACTION KINETICS
SULFUR COMPOUNDS
METHYLATION
IN VIVO
MICE
SULFIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
CHALCOGENIDES
CHEMICAL REACTIONS
ENZYMES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
REACTION KINETICS
RODENTS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques