The discovery of mercapturic acids occurred in two labs in 1879. E.Baumann and C.Preuss were members of the Physiological Institute of the University of Berlin and examined the metabolism of bromobenzene fed to dogs. They discovered that, in addition to sulfate(s) there was a second sulfur containing metabolite in the urine of the dogs which they named as a mercapturic acid.1
In addition, they found out that hydrolysis of this metabolite yielded acetic acid and para-bromo phenylmercaptan. In the same year M.Jaffe, in Konigsberg, elucidated the biotransformation of chlorobenzene and iodobenzene finding that they also formed mercapturic acids.2 Only 5 years later Baumann reported the correct structure of the mercapturic acids as acetyl cysteine conjugates3
The complete metabolic sequence however, starting with glutathione conjugation, remained unknown for over 70 years. The relationship between glutathione conjugation and the formation of mercapturic acids was initially characterized in 1959 at University of Birmingham by S.P.James, M.M.Barnes P.B.Wood, H.G.Bray and T.J.Franklin. They showed that administration of a mercapturic acid precursor led to a drop in liver glutathione levels commensurate with the amount of mercapturic acid formed.4 They went on to show that S-(p-Cl-benzyl) glutathione was converted in vitro to S-p-Cl benzyl cysteine5 and this compound could be acetylated by liver preparations.6 Two years later, J.Booth, E.Boyland and P. Sims described the direct enzymatic formation of glutathione conjugates7 providing the backdrop for the investigation of glutathione tranferases in modern times.
	In 1888 J. de Rey-Pailhade described his discovery of a substance he found widely distributed in nature having the ability to hydrogenate sulfur.8He named the substance philothion based on it's reactivity towards sulfur. F.G.Hopkins was able to crystallize the substance from yeast extracts and initially characterized it as a dipeptide of glutamic acid and cysteine.9 Based on this structure Hopkins suggested the name "glutathione" After work by Hunter and Eagles called the dipeptide structure into question,10 Hopkins used improved purification techniques to establish the fact that glutathione was in fact a tripeptide containing cysteine, glutamic acid and glycine.11 Pirie and Pinhey deduced the tripeptide sequence based on titration data12 and this was later confirmed by the synthetic work of Harington and Mead.13
References:1E.Baumann and C.Preuss, Ber.deut.chem.Ges.,12:806(1879)2 M.Jaffe, Ber.deut.chem.Ges.12:1092(1879).3 E. Baumann, Z.Physiol.Chem.8:299 (1884)4 M.M.Barnes, S.P.James and P.B.Wood, Biochem.J.71:680(1959)5 H.G.Bray, T.J.Franklin and S.P.James, Biochem.J.71:690(1959)6 G.Bray, T.J.Franklin and S.P.James, Biochem. J.73:465(1959).7 J.Booth, E.Boyland and P.Sims, Biochem.J.79:516(1961) 8J. de Rey Pailhade, Bull.Soc.Hist.Nat.Toulouse,173(1888)9 F.G.Hopkins, Biochem.J. 15:286 (1921)10G. Hunter, B.A.Eagles, J.Biol. Chem. 72:703(1927)11F.G.Hopkins,J.Biol.Chem.84:269(1929) 12N.W.Pirie, and K.G.Pinhey, J.Biol. Chem. 84:657(1929)13C.R.Harington, and T.H.Mead,Biochem. J.29:1602(1935)