Xenobiotic Metabolism

Schematic representation of glutathione-s-transferase protein subunit

Mercapturic Acid Formation

Mercapturic acids were discovered in two labs in 1879. Members of the Physiological Institute of the University of Berlin, E. Baumann and C. Preuss, examined the metabolism of bromobenzene fed to dogs. They discovered, in addition to sulfate(s), a second sulfur-containing metabolite in the dogs’ urine which they named a mercapturic acid. They also discovered that hydrolysis of the metabolite yielded acetic acid and para-bromophenylmercapturic acid.

In the same year, M. Jaffe independently elucidated the biotransformation of aromatic compounds, finding that chlorobenzene and iodobenzene also formed mercapturic acids. Only five years later, Baumann reported the correct structure of the mercapturic acids as acetyl cysteine conjugates.

The whole metabolic pathway, however—starting with the glutathione conjugation—remained unknown for a long time. Glutathione was discovered by M.J. de Rey Pailhade at the end of the 19th century as the substance “hydrogénant le soufre,” which was renamed by F.G. Hopkins. Hopkins first characterised the compound as a dipeptide of glutamic acid and cysteine and suggested the correct structure later to be a tripeptide which also contains glycine. The relationship between glutathione conjugation and the formation of mercapturic acids was characterised in 1959 by M.M. Barnes, et al., who established the origin of mercapturic acids as glutathione conjugates.

Two years later, J. Booth, et al., described for the first time the enzymatic formation of glutathione conjugates, which led to modern investigation of glutathione tranferases.

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