Incorporation of radiolabelled amino acids into the sulphur-containing metabolites of paracetamol by the hamster

Abstract

1. Various radiolabelled forms of the amino acids cysteine, methionine and serine were co-administered with paracetamol to the hamster to investigate the biosynthesis of the thiomethyl metabolites of paracetamol. T.l.c. and h.p.l.c. were used to determine the presence of sulphur-containing metabolites in the urine.

2. Paracetamol sulphate and the 3-cysteine, mercapturate and thiomethyl derivatives were all detected in urine, along with the 3-methylsulphoxide after hydrolysis. No paracetamol-3-methylsulphone was detected.

3. Both cysteine and methionine acted as sulphur donors via glutathione. The methyl group of the thiomethyl derivatives originated from methionine in a reaction system believed to involve cysteine conjugate-β-lyase and the thiomethyl shunt.