title: Modular isotopomer synthesis of γ-hydroxybutyric acid for a quantitative analysis of metabolic fates.
abstract: 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.
authors.affiliation: Departments of †Chemistry and ‡Nutrition, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Sushabhan
authors.initials: S
authors.lastname: Sadhukhan
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Tochtrop
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D005680:gamma-Aminobutyric Acid / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D005680:gamma-Aminobutyric Acid