4.5 Article

Metabolism of γ-hydroxybutyrate in perfused rat livers

期刊

BIOCHEMICAL JOURNAL
卷 444, 期 -, 页码 333-341

出版社

PORTLAND PRESS LTD
DOI: 10.1042/BJ20112046

关键词

alpha-oxidation; beta-oxidation; 4-hydroxyacid; gamma-hydroxybutyrate (GHB); mass isotopomer analysis; metabolomics

资金

  1. National Institutes of Health [R33DK070291, R01ES013925, R01HL053315]
  2. Cleveland Mt. Sinai Health Care Foundation

向作者/读者索取更多资源

GHB (gamma-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 gamma-aminobutyrate via succinic semialdehyde. Also, GHB undergoes (i) beta-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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