Metabolism of γ-hydroxybutyrate in perfused rat livers.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, G-F; Sadhukhan, S; Ibarra, RA; Lauden, SM; Chuang, C-Y; Sushailo, S; Chatterjee, P; Anderson, VE; Tochtrop, GP; Brunengraber, H

Published Date

  • June 1, 2012

Published In

Volume / Issue

  • 444 / 2

Start / End Page

  • 333 - 341

PubMed ID

  • 22428548

Pubmed Central ID

  • 22428548

Electronic International Standard Serial Number (EISSN)

  • 1470-8728

Digital Object Identifier (DOI)

  • 10.1042/BJ20112046

Language

  • eng

Conference Location

  • England