Effects of methionine and other sulfur compounds on drug conjugations

Abstract

Conjugation reactions in the detoxification of drugs and environmental chemicals occur with various sulfur-containing substances. These reactions include: (1) glutathione (GSH, reduced glutathione) conjugation with subsequent mercapturic acid synthesis; (2) sulfate conjugation (sulfate ester synthesis); (3) methylation by S-adenosylmethionine (SAM); (4) thiosulfate conjugation of the cyanide ion, resulting in thiocyanate synthesis; (5) chelation of toxic metals by metallothionein, a sulfhydryl-rich protein. Of the drug conjugation reactions affected by methionine and cysteine intake and metabolism, sulfate and glutathione reactions have the greatest physiological significance. Much study has been devoted to the determination of intraand extracellular concentrations and transport of sulfur-containing compounds, and their relation to xenobiotic metabolism. Studies of the influence of dietary sulfur amino acid intake on the utilization during xenobiotic metabolism of sulfur-containing compounds are more limited, however. This review describes these studies as they relate to sulfur amino acid nutrition and Phase II drug conjugations. The major focus is on the effect of dietary methionine and cysteine intake on sulfate and glutathione conjugation reactions.