Mercapturic acid, synthesis

Hughey RP, Rankin BB, Elce JS, and Curthoys NP. Specificity of a particulate rat renal peptidase and its localization along with other enzymes of mercapturic acid synthesis. Archives of biochemistry and biophysics 186 211-217,1978. 

Nadelmann, L., Tjornelund, J., Hansen, S.H., Cornett, C., Sidelmann, U.G., Braumann, Christensen, E., and Christensen, S.B., Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A, Xenobiotica, 27, 667, 1997. 

Reactive Metabolites or Intermediates Reactive metabolites are chemically unstable and often rapidly bind to proteins or glutathione (GSH). In general, GSH adducts are not present at significant levels in circulation, because they undergo rapid elimination via direct biliary excretion or further metabolism to mercapturic acids that are excreted into urine. Reactive metabolites can be monitored via quantitative analysis of their GSH adducts or mercapturic acids in excreta. However, it is not practical to test the toxicity of reactive metabolites on animals directly since the synthesis and dosing preparation of reactive metabolites are extremely difficult or impossible due to their chemical instability (Davis-Bruno and Atrakchi, 2006). 

Certain metabolic reactions of cysteine do not seem to fit into any known metabolic pathway, e.g., the formation of 2-iminothiazolidine-4-carboxylic acid in rats injected with NaCN (66), or the reaction of formaldehyde with cysteine to form thiazolidine-4-carboxylic acid, which is subsequently dehydrogenated to thiazoline-4-carboxylate (66). Mer-capturic acids also belong to this group. The study of the enzymic synthesis of mercapturic acids deserves more attention since this process is rather general in many species. The fundamental reaction in mercapturic acid formation is the conjugation of a variety of substances with the S atom of Af-acetylcysteine. 

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