Identification of Metabolites of [1,2,3-13C]Propargyl Alcohol in Mouse Urine by 13C NMR and Mass Spectrometry and Comparison to Rat

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• 作者：Ali R. Banijamali ; Yaodong Xu ; Vincent DeMatteo ; Richard J. Strunk ; and Susan J. Sumner
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2000
• 出版时间：October 2000
• 年：2000
• 卷：48
• 期：10
• 页码：4693 - 4710
• 全文大小：268K
• 年卷期：v.48,no.10(October 2000)
• ISSN：1520-5118

文摘

Species differences in the metabolism of acetylenic compounds commonly used in the formulationof pharmaceuticals and pesticides have not been investigated. To better understand the in vivoreactivity of this bond, the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, was examined inrats and mice. An earlier study (Banijamali, A. R.; Xu, Y.; Strunk, R. J.; Gay, M. H.; Ellis, M. C.;Putterman, G. J. J. Agric. Food Chem. 1999, 47, 1717-1729) in rats revealed that PA undergoesextensive metabolism primarily via glutathione conjugation. The current research describes themetabolism of PA in CD-1 mice and compares results for the mice to those obtained for rats. [1,2,3-¹³C;2,3-¹⁴C]PA was administered orally to the mice. Approximately 60% of the dose was excreted inurine by 96 h. Metabolites were identified, directly, in whole urine by 1- and 2-D ¹³C NMR andHPLC/MS and by comparison with the available reference compounds. The proposed metabolicpathway involves glucuronide conjugation of PA to form 2-propyn-1-ol-glucuronide as well asoxidation of PA to the proposed intermediate 2-propynal. The aldehyde undergoes conjugation withglutathione followed by further metabolism to yield as final products 3,3-bis[(2-acetylamino-2-carboxyethyl)thio]-1-propanol, 3-[(2-acetylamino-2-carboxyethyl)thio]-3-[(2-amino-2-carboxyethyl)thio]-1-propanol, 3,3-bis[(2-amino-2-carboxyethyl)thio]-1-propanol, 3-[(2-amino-2-carboxyethyl)thio]-2-propenoic acid, and 3-[(2-formylamino-2-carboxyethyl)thio]-2-propenoic acid. A small portion of2-propynal is also oxidized to result in the excretion of 2-propynoic acid. On the basis of urinarymetabolite data, qualitative and quantitative differences are noted between rats and mice in theformation of the glucuronide conjugate of PA and in the formation of 2-propynoic acid and metabolitesderived from glutathione. These metabolites represent further variation on glutathione metabolismfollowing its addition to the carbon-carbon triple bond compared to those described for the rat.Keywords: 2-Propyn-1-ol mouse metabolism; glutathione conjugates; glucuronide conjugate