title: A mechanism for the formation of bis-glutathione conjugates of propargyl alcohol.
abstract: 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.
authors.affiliation: Metabolism Chemistry, Crop Protection R&D, Crompton Corp, Middlebury, CT 06749, USA. ali_banijamali@cromptoncorp.com
authors.forename: Ali R
authors.initials: AR
authors.lastname: Banijamali
authors.forename: Vincent
authors.initials: V
authors.lastname: DeMatteo
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Sumner
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D020005:Propanols / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000480:Alkynes; D020005:Propanols; C028255:propargyl alcohol; D005978:Glutathione