Biochemical studies of toxic agents. 15. The biosynthesis of ethylmercapturic acid sulphoxide

Abstract

The oxidation of a number of thio ethers to Soxides (sulphoxidation) has been observed in bio- logical systems.Compounds metabolized by mam- mals to the sulphoxide include chlorpromazine (Salzman & Brodie, 1956), 1,2-diphenyl-4-(phenylthioethyl)pyrazolidine-3,5-dione (Bums et al. 1957) and promazine (Walkenstein & Seifter, 1959).The oxidation occurs in micro-organisms: (-) -biotin sul- phoxide is produced by A8pergillu8 niger (Wright, Cresson, Valiant, Wolf & Folkers, 1954) and 17fl- acetoxy-7oc-methylthioandrost-4-en-3-one is con- verted by Catonectria decora into 17fi-hydroxy-7ctmethylsulphinylandrost-4-en-3-one (Holmlund et al. 1962).Several examples of the occurrence of sulphoxides in plants are known.They are principally S-alkyl-L-cysteine S-oxides, their derivatives and w-methylsulphinylalkyl isothiocyanate glucosides, and they have been reviewed recently by Virtanen (1962).The sulphoxidation of 4,4'-diaminodiphenyl sul- phide has been observed in vitro with a preparation of guinea-pig-liver microsomes which required NAtbPH2 and oxygen for maximum activity (Gillette & Kamm, 1960), and evidence for the enzymic sulphoxidation of S-methyl-L-cysteine in leaves has been presented by Arnold & Thompson (1962).Evidence for the occurrence of ethylmercapturic acid sulphoxide (N-acetyl-S-ethyl-L-cysteine S- oxide) in the urine of rats that had been dosed with bromoethane was presented by Thomson & Young (1960).The present paper gives a fuller account of this work together with evidence for the metabolic conversion of S-ethyl-L-cysteine, S-ethyl-L-cysteine S-oxide and ethylmercapturic acid into ethylmer- capturic acid sulphoxide, and describes the isola- tion of (+)-ethylmercapturic acid sulphoxide, as its dicyclohexylammonium salt, from the urine of rats to which S-ethyl-L-cysteine had been admini- stered. MATERIALSAll melting points are uncorrected.Elementary analyses were carried out by Weiler and Strauss, Oxford.