Metabolism of γ-hydroxybutyrate in perfused rat livers.
GHB (γ-hydroxybutyrate) is both a neurotransmitter and a drug of abuse (date-rape drug). We investigated the catabolism of this compound in perfused rat livers. Using a combination of metabolomics and mass isotopomer analysis, we showed that GHB is metabolized by multiple processes, in addition to its previously reported metabolism in the citric acid cycle via oxidation to succinate. A substrate cycle operates between GHB and γ-aminobutyrate via succinic semialdehyde. Also, GHB undergoes (i) β-oxidation to glycolyl-CoA+acetyl-CoA, (ii) two parallel processes which remove C-1 or C-4 of GHB and form 3-hydroxypropionate from C-2+C-3+C-4 or from C-1+C-2+C-3 of GHB, and (iii) degradation to acetyl-CoA via 4-phosphobutyryl-CoA. The present study illustrates the potential of the combination of metabolomics and mass isotopomer analysis for pathway discovery.
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Related Subject Headings
- Substrate Specificity
- Sodium Oxybate
- Rats, Sprague-Dawley
- Rats
- Perfusion
- Liver
- Biochemistry & Molecular Biology
- Animals
- 3101 Biochemistry and cell biology
- 11 Medical and Health Sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Substrate Specificity
- Sodium Oxybate
- Rats, Sprague-Dawley
- Rats
- Perfusion
- Liver
- Biochemistry & Molecular Biology
- Animals
- 3101 Biochemistry and cell biology
- 11 Medical and Health Sciences