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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Research Article|
May 11 2012
Metabolism of γ-hydroxybutyrate in perfused rat livers
Guo-Fang Zhang;
Guo-Fang Zhang
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Sushabhan Sadhukhan;
Sushabhan Sadhukhan
†Department of Chemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Rafael A. Ibarra;
Rafael A. Ibarra
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Stephanie M. Lauden;
Stephanie M. Lauden
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Chia-Ying Chuang;
Chia-Ying Chuang
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Sophia Sushailo;
Sophia Sushailo
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Priya Chatterjee;
Priya Chatterjee
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Vernon E. Anderson;
Vernon E. Anderson
‡Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Gregory P. Tochtrop;
Gregory P. Tochtrop
†Department of Chemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
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Henri Brunengraber
Henri Brunengraber
1
*Department of Nutrition, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.
1To whom correspondence should be addressed (email hxb8@case.edu).
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Publisher: Portland Press Ltd
Received:
November 18 2011
Revision Received:
March 08 2012
Accepted:
March 19 2012
Accepted Manuscript online:
March 19 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 444 (2): 333–341.
Article history
Received:
November 18 2011
Revision Received:
March 08 2012
Accepted:
March 19 2012
Accepted Manuscript online:
March 19 2012
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. Biochem J 1 June 2012; 444 (2): 333–341. doi: https://doi.org/10.1042/BJ20112046
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