Thioacylating intermediates as metabolites of S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2,2-trichlorovinyl)-L-cysteine formed by cysteine conjugate beta-lyase

Chem Res Toxicol. 1988 May-Jun;1(3):175-8. doi: 10.1021/tx00003a008.

Abstract

The bioactivation mechanism of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) was studied with cysteine conjugate beta-lyase (beta-lyase) from Salmonella typhimurium and with the pyridoxal phosphate model N-dodecylpyridoxal bromide (PL-Br) as catalysts and with GC/MS to identify the metabolites formed. PL-Br converted S-2-benzothiazolyl-L-cysteine to 2-mercaptobenzothiazole and S-benzyl-L-cysteine to benzyl mercaptan, demonstrating the ability of PL-Br to serve as a model for beta-lyase. PL-Br and bacterial beta-lyase converted DCVC to chloroacetic acid and chlorothionoacetic acid and TCVC to dichloroacetic acid. Incubations of PL-Br with the S-conjugates in the presence of diethylamine resulted in the formation of N,N-diethylchlorothioacetamide from DCVC and of N,N-diethyldichlorothioacetamide from TCVC. Attempts to trap the enethiols, which are the expected initial products formed by beta-elimination, by reaction with methyl iodide in incubations with the beta-lyase model were not successful. The formation of thioacylating agents from the enethiols may contribute to the cytotoxic and mutagenic effects of DCVC and TCVC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acylation
  • Biotransformation
  • Carbon-Sulfur Lyases*
  • Cysteine / analogs & derivatives*
  • Cysteine / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Lyases / metabolism*
  • Magnetic Resonance Spectroscopy
  • Salmonella typhimurium / enzymology

Substances

  • S-(1,2-dichlorovinyl)cysteine
  • S-(1,2,3-trichlorovinyl)cysteine
  • Lyases
  • Carbon-Sulfur Lyases
  • S-alkylcysteine lyase
  • Cysteine