1. The formation of 2-hydroxypropylmercapturic acid from 1-halogenopropanes in the rat
E A Barnsley Biochem J. 1966 Aug;100(2):362-72. doi: 10.1042/bj1000362.
1. 2-Hydroxypropylmercapturic acid, i.e. N-acetyl-S-(2-hydroxypropyl)-l-cysteine, has been isolated, as the dicyclohexylammonium salt, from the urine of rats dosed with 1-bromopropane. 2. The formation of the same metabolite from 1-chloropropane, 1-iodopropane, 1,2-epoxypropane and 1-chloropropan-2-ol has been demonstrated by chromatographic examination of the urine excreted by rats after they had been dosed with these compounds. 3. (+)- and (-)-Dicyclohexylammonium 2-hydroxypropylmercapturate have been prepared by fractional crystallization of the mixture of isomers obtained by two methods: the reaction of 1,2-epoxypropane with l-cysteine followed by acetylation, and the reduction of 2-oxopropylmercapturic acid. 4. The following compounds have also been prepared: S-(3-hydroxypropyl)-l-cysteine, (+)- and (-)-S-(2-hydroxypropyl)-l-cysteine, dicyclohexylammonium 3-hydroxypropylmercapturate, (+)- and (-)-dicyclohexylammonium 2-hydroxy-1-methylethylmercapturate, and (+)- and (-)-dicyclohexylammonium 1-(ethoxycarbonyl)ethylmercapturate.
2. Biochemical studies of toxic agents. The metabolism of 1- and 2-bromopropane in rats
E A Barnsley, T H Grenby, L Young Biochem J. 1966 Jul;100(1):282-8. doi: 10.1042/bj1000282.
1. (+)-n-Propylmercapturic acid sulphoxide, i.e. (+)-N-acetyl-S-n-propyl-l-cysteine S-oxide, was prepared as the dicyclohexylammonium salt, (-)-n-propyl-mercapturic acid sulphoxide was prepared as the free acid, and S-isopropyl-l-cysteine and isopropylmercapturic acid were also prepared. 2. The metabolism of 1- and 2-bromopropane was studied by radiochromatographic examination of the urine excreted by rats that had been fed with a diet containing (35)S-labelled yeast and then injected subcutaneously with these compounds. In addition to n-propyl-mercapturic acid and 2-hydroxypropylmercapturic acid, the excretion of which has already been reported, n-propylmercapturic acid sulphoxide was shown to be a metabolite of 1-bromopropane. Sulphur-containing metabolites of 2-bromopropane, if present in the urine at all, were there in very small amounts. 3. n-Propylmercapturic acid and isopropylmercapturic acid were isolated from the urine of rats that had been injected subcutaneously with S-n-propyl-l-cysteine and S-isopropyl-l-cysteine respectively.
3. Some metabolites of 1-bromobutane in the rabbit and the rat
S P James, D A Jeffery, R H Waring, P B Wood Biochem J. 1968 Oct;109(5):727-36. doi: 10.1042/bj1090727.
1. Rabbits and rats dosed with 1-bromobutane excrete in urine, in addition to butylmercapturic acid, (2-hydroxybutyl)mercapturic acid, (3-hydroxybutyl)mercapturic acid and 3-(butylthio)lactic acid. 2. Although both species excrete both the hydroxybutylmercapturic acids, only traces of the 2-isomer are excreted by the rabbit. The 3-isomer has been isolated from rabbit urine as the dicyclohexylammonium salt. 3. 3-(Butylthio)lactic acid is formed more readily in the rabbit; only traces are excreted by the rat. 4. Traces of the sulphoxide of butylmercapturic acid have been found in rat urine but not in rabbit urine. 5. In the rabbit about 14% and in the rat about 22% of the dose of 1-bromobutane is excreted in the form of the hydroxymercapturic acids. 6. Slices of rat liver incubated with S-butylcysteine or butylmercapturic acid form both (2-hydroxybutyl)mercapturic acid and (3-hydroxybutyl)mercapturic acid, but only the 3-hydroxy acid is formed by slices of rabbit liver. 7. S-Butylglutathione, S-butylcysteinylglycine and S-butylcysteine are excreted in bile by rats dosed with 1-bromobutane. 8. Rabbits and rats dosed with 1,2-epoxybutane excrete (2-hydroxybutyl)mercapturic acid to the extent of about 4% and 11% of the dose respectively. 9. The following have been synthesized: N-acetyl-S-(2-hydroxybutyl)-l-cysteine [(2-hydroxybutyl)mercapturic acid] and N-acetyl-S-(3-hydroxybutyl)-l-cysteine [(3-hydroxybutyl)mercapturic acid] isolated as dicyclohexylammonium salts, N-toluene-p-sulphonyl-S-(2-hydroxybutyl)-l-cysteine, S-butylglutathione and N-acetyl-S-butylcysteinyl-glycine ethyl ester.
