Modular Isotopomer Synthesis of 纬-Hydroxybutyric Acid for a Quantitative Analysis of Metabolic Fates

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• 作者：Sushabhan Sadhukhan ; Guo-Fang Zhang ; Gregory P. Tochtrop
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：August 15, 2014
• 年：2014
• 卷：9
• 期：8
• 页码：1706-1711
• 全文大小：334K
• ISSN：1554-8937

文摘

Herein we report a study combining metabolomics and mass isotopomer analysis used for investigation of the biochemical fate of 纬-hydroxybutyric acid (GHB). Using various ¹³C incorporation labeling patterns into GHB, we have discovered that GHB is catabolized by previously unknown processes that include (i) direct 尾-oxidation to acetyl-CoA and glycolate, (ii) 伪-oxidation to 3-hydroxypropionyl-CoA and formate, and (iii) cleavage of C-4 to yield 3-hydroxypropionate and CO₂. We further utilized the unique attributes of our labeling patterns and the resultant isotopomers to quantitate relative flux down the identified pathways.