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.
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.
Dekant
W
W
Institut für Toxikologie, Universität Würzburg, Federal Republic of Germany.
Berthold
K
K
Vamvakas
S
S
Henschler
D
D
Anders
M W
MW
D000215:Acylation; D001711:Biotransformation; D013437:Carbon-Sulfur Lyases; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008190:Lyases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D012486:Salmonella typhimurium / Q000201:enzymology
C039961:S-(1,2-dichlorovinyl)cysteine; C072640:S-(1,2,3-trichlorovinyl)cysteine; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D003545:Cysteine