title: Phenotypic and chemotypic studies using Arabidopsis and yeast reveal that GHB converts to SSA and induce toxicity.
abstract: γ-Hydroxybutyric acid (GHB) is a naturally occurring compound. It is detected in organisms such as yeasts, plants and mammals. GHB is produced from the reduction of succinic semialdehyde (SSA) by the activity of GHB dehydrogenase. Arabidopsis genome contains two GHB dehydrogenase encoding genes. The accumulation of GHB in ssadh mutants led to the speculation that GHB is the cause of aberrant phenotypes. Conversely, the accumulation of GHB in Arabidopsis plants subjected to abiotic stresses was described as a way of avoiding SSA induced damage. To resolve these contrasting views on GHB, we examined the effect of exogenous GHB and SSA on the growth of yeast and Arabidopsis plants. GHB concentrations up to 1.5 mM didn't affect shoots of Arabidopsis plants; however, root growth was inhibited. In contrast, 0.3 mM SSA has severely affected the growth of plants. Treatment of yeast wild-type strain with 10 mM SSA and 10 mM GHB didn't affect the growth. However, the growth of yeast uga2 mutant was greatly inhibited by the same concentration of SSA, but not GHB. Metabolic analysis and enzyme activity assay on native gel showed that Arabidopsis, but not yeast, possesses a GHB dehydrogenase activity that converts GHB back to SSA. The enzymatic assay has also indicated the existence of an additional GHB dehydrogenase encoding gene(s) in Arabidopsis genome. Taken together, we conclude that GHB is less toxic than SSA. Its accumulation in ssadh mutants and during abiotic stresses is a response to avoid the SSA induced damage.
authors.affiliation: Cologne Biocenter, Botanical Institute II, University of Cologne, Zülpicher Str. 47b, 50674, Cologne, Germany. derejeworku1@yahoo.com.
authors.forename: Dereje Worku
authors.identifier: http://orcid.org/0000-0003-3167-7412
authors.initials: DW
authors.lastname: Mekonnen
authors.affiliation: Cologne Biocenter, Botanical Institute II, University of Cologne, Zülpicher Str. 47b, 50674, Cologne, Germany.|Division of Biochemistry, Department Biology, University Erlangen-Nuremberg, Staudtstr. 5, 91058, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Ludewig
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D017360:Arabidopsis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002244:Carbon / Q000494:pharmacology; D002952:Citric Acid Cycle / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006885:Hydroxybutyrates / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D005680:gamma-Aminobutyric Acid; D002244:Carbon; D000445:Aldehyde Oxidoreductases; C009338:succinic semialdehyde
keywords: GABA shunt; GHB; GHB dehydrogenase; SSA; SSADH; uga2