Thioacylating agents as ultimate intermediates in the beta-lyase catalysed metabolism of S-(pentachloro-butadienyl)-L-cysteine.
The transformation of the hexachloro-1,3-butadiene metabolite S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (PCBC) by bacterial cysteine conjugate beta-lyase (beta-lyase) and by N-dodecylpyridoxal bromide (PLP-Br) was investigated using GC/MS to identify products formed. PCBC was transformed by both bacterial beta-lyase and PLP-Br to the major products 2,3,4,4-tetrachlorobutenoic acid and 2,3,4,4-tetrachlorothiobutenoic acid, and to the minor metabolites trichloroacetic acid and S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-mercaptoacetic acid. In the presence of diethylamine as model nucleophile, PLP-Br transformed PCBC to yield 2,3,4,4-tetrachlorothiobutenoic acid diethylamide; attempts to trap 1,2,3,4,4-pentachlorobutadienyl thiol, the initial metabolite formed by beta-elimination from PCBC, were unsuccessful. The results obtained suggest that the formation of a thioacylating intermediate (a thioketene or a thiono acyl chloride) may be the decisive reaction during the beta-lyase dependent activation of PCBC.
Dekant
W
W
Institut für Toxikologie, Universität Würzburg, F.R.G.
Berthold
K
K
Vamvakas
S
S
Henschler
D
D
D002070:Butadienes / Q000378:metabolism*; D013437:Carbon-Sulfur Lyases; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008190:Lyases / Q000378:metabolism*; D013058:Mass Spectrometry; D015394:Molecular Structure; D011730:Pyridoxal / Q000031:analogs & derivatives*
D002070:Butadienes; D011730:Pyridoxal; C041277:1-dodecylpyridoxal; C039330:S-pentachlorobuta-1,3-dien-yl-cysteine; C001335:hexachlorobutadiene; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D003545:Cysteine