title: Metabolism of γ-hydroxybutyrate in perfused rat livers.
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 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.
authors.affiliation: Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: Sushabhan
authors.initials: S
authors.lastname: Sadhukhan
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Ibarra
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Lauden
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Chuang
authors.forename: Sophia
authors.initials: S
authors.lastname: Sushailo
authors.forename: Priya
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Anderson
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Tochtrop
authors.forename: Henri
authors.initials: H
authors.lastname: Brunengraber
mesh_terms: D000818:Animals; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D012978:Sodium Oxybate