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A mechanism for the formation of bis‐glutathione conjugates of propargyl alcohol
Author(s) -
Banijamali Ali R,
DeMatteo Vincent,
Sumner Susan J
Publication year - 2003
Publication title -
pest management science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 125
eISSN - 1526-4998
pISSN - 1526-498X
DOI - 10.1002/ps.641
Subject(s) - glutathione , chemistry , metabolite , propargyl , alcohol , conjugate , propargyl alcohol , conjugated system , metabolism , stereochemistry , biochemistry , organic chemistry , catalysis , enzyme , mathematical analysis , polymer , mathematics
Our earlier research clearly revealed glutathione (GSH) conjugation as a major pathway for the metabolism of propargyl alcohol (2‐propyn‐1‐ol) in rats and in mice. The identification of the metabolite 3,3‐bis[(2‐acetylamino‐2‐carboxyethyl)thio]‐1‐propanol (I) and its congeners represented the first example of multi‐glutathione addition to a triple bond, and invoked further research to determine the mechanism for bis‐conjugation. To determine whether GSH conjugated directly with propargyl alcohol or after oxidation of the latter to 2‐propynal, urinary metabolites from rats administered deuterium‐labeled propargyl alcohol were characterized. Following TLC separation and HPLC purification, mass spectrometry was used to show a single mass unit increase for metabolite I over that of the chemically synthesized standard. This result indicates that conjugation of propargyl alcohol with GSH to form the bis‐conjugates occurred after initial oxidation to 2‐propynal, a reaction that is analogous to a Michael addition. © 2003 Society of Chemical Industry