Identification of Metabolites of [1,2,3-13C]Propargyl Alcohol in Rat Urine by 13C NMR and Mass Spectrometry
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- 作者：Ali R. Banijamali ; Yaodong Xu ; Richard J. Strunk ; Michael H. Gay ; Michael C. Ellis ; Gerald J. Putterman ; and Susan J. Sumner
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：1999
- 出版时间：April 1999
- 年：1999
- 卷：47
- 期：4
- 页码：1717 - 1729
- 全文大小：242K
- 年卷期：v.47,no.4(April 1999)
- ISSN：1520-5118
文摘
Little is known about the metabolism of acetylenic (C
C) compounds commonly used in theformulation of pesticides. To better understand the in vivo reactivity of this bond, we examined themetabolism of propargyl alcohol (PA), 2-propyn-1-ol, used extensively in the chemical industry. [1,2,3-13C, 2,3-14C]PA was administered orally to male Sprague-Dawley rats. Approximately 56% of thedose was excreted in urine by 96 h. Major metabolites were characterized, directly, in the wholeurine by one- and two-dimensional 13C NMR. To determine the complete structures of metabolitesof PA, rat urine was also subjected to TLC followed by purification of separated TLC bands onHPLC. The purified metabolites were identified by 13C NMR and mass spectrometry and bycomparison with available synthetic standards. The proposed metabolic pathway involves oxidationof propargyl alcohol to 2-propynoic acid and further detoxification via glutathione conjugation toyield as final products: 3,3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, 3-(carboxymethylthio)-2-propenoic acid, 3-(methylsulfinyl)-2-(methylthio)-2-propenoic acid, 3-[[2-(acetylamino)-2-carboxyethyl]thio]-3-[(2-amino-2-carboxyethyl)thio]-1-propanol and 3-[[2-(acetylamino)-2-carboxyethyl]sulfinyl]-3-[2-(acetylamino)-2-carboxyethyl]thio]-1-propanol. These unique metabolites havenot been reported previously and represent the first example of multiple glutathione additions tothe carbon-carbon triple bond.Keywords: Propargyl alcohol metabolism; metabolism of carbon-carbon triple bond; dicysteinylconjugates; 2-propyn-1-ol
C) compounds commonly used in theformulation of pesticides. To better understand the in vivo reactivity of this bond, we examined themetabolism of propargyl alcohol (PA), 2-propyn-1-ol, used extensively in the chemical industry. [1,2,3-13C, 2,3-14C]PA was administered orally to male Sprague-Dawley rats. Approximately 56% of thedose was excreted in urine by 96 h. Major metabolites were characterized, directly, in the wholeurine by one- and two-dimensional 13C NMR. To determine the complete structures of metabolitesof PA, rat urine was also subjected to TLC followed by purification of separated TLC bands onHPLC. The purified metabolites were identified by 13C NMR and mass spectrometry and bycomparison with available synthetic standards. The proposed metabolic pathway involves oxidationof propargyl alcohol to 2-propynoic acid and further detoxification via glutathione conjugation toyield as final products: 3,3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, 3-(carboxymethylthio)-2-propenoic acid, 3-(methylsulfinyl)-2-(methylthio)-2-propenoic acid, 3-[[2-(acetylamino)-2-carboxyethyl]thio]-3-[(2-amino-2-carboxyethyl)thio]-1-propanol and 3-[[2-(acetylamino)-2-carboxyethyl]sulfinyl]-3-[2-(acetylamino)-2-carboxyethyl]thio]-1-propanol. These unique metabolites havenot been reported previously and represent the first example of multiple glutathione additions tothe carbon-carbon triple bond.Keywords: Propargyl alcohol metabolism; metabolism of carbon-carbon triple bond; dicysteinylconjugates; 2-propyn-1-ol