Metabolism of γ-hydroxybutyrate in perfused rat livers.

Guo-Fang Zhang, Sushabhan Sadhukhan, Rafael A Ibarra, Stephanie M Lauden, Chia-Ying Chuang, Sophia Sushailo, Priya Chatterjee, Vernon E Anderson, Gregory P Tochtrop, Henri Brunengraber

Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

The Biochemical journal 2012 Jun 1

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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.

Citation

Guo-Fang Zhang, Sushabhan Sadhukhan, Rafael A Ibarra, Stephanie M Lauden, Chia-Ying Chuang, Sophia Sushailo, Priya Chatterjee, Vernon E Anderson, Gregory P Tochtrop, Henri Brunengraber. Metabolism of γ-hydroxybutyrate in perfused rat livers. The Biochemical journal. 2012 Jun 1;444(2):333-41