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- Title
Metabolism of γ -hydroxybutyrate in perfused rat livers.
- Authors
ZHANG, Guo-Fang; SADHUKHAN, Sushabhan; IBARRA, Rafael A.; LAUDEN, Stephanie M.; CHUANG, Chia-Ying; SUSHAILO, Sophia; CHATTERJEE, Priya; ANDERSON, Vernon E.; TOCHTROP, Gregory P.; BRUNENGRABER, Henri
- Abstract
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 ? -aminobutyrate via succinic semialdehyde. Also, GHB undergoes (i) ß-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.
- Subjects
GAMMA-hydroxybutyrate; METABOLISM; NEUROTRANSMITTERS; LIVER diseases; KREBS cycle; LABORATORY rats
- Publication
Biochemical Journal, 2012, Vol 444, Issue 2, p333
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20112046