Modular Isotopomer Synthesis of γ-Hydroxybutyric Acid for a Quantitative Analysis of Metabolic Fates
Author(s) -
Sushabhan Sadhukhan,
GuoFang Zhang,
Gregory P. Tochtrop
Publication year - 2014
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/cb500380b
Subject(s) - isotopomers , formate , chemistry , metabolic pathway , metabolome , yield (engineering) , metabolomics , biochemistry , isotopic labeling , flux (metallurgy) , metabolism , metabolite , chromatography , organic chemistry , catalysis , materials science , molecule , metallurgy
Herein we report a study combining metabolomics and mass isotopomer analysis used for investigation of the biochemical fate of γ-hydroxybutyric acid (GHB). Using various (13)C incorporation labeling patterns into GHB, we have discovered that GHB is catabolized by previously unknown processes that include (i) direct β-oxidation to acetyl-CoA and glycolate, (ii) α-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.
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