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Succinic semialdehyde

Succinic semialdehyde (SSA) is a GABA and GHB metabolite. It is formed from GABA by the action of GABA transaminase (4-aminobutyrate aminotransferase) and further oxidised to become succinic acid, which enters TCA cycle. SSA is oxidized into succinic acid by the enzyme succinic semialdehyde dehydrogenase, which uses NAD+ as a cofactor.  When the oxidation of succinic semialdehyde to succinic acid is impaired, accumulation of succinic semialdehyde takes place which leads to succinic semialdehyde dehydrogenase deficiency.

In addition to the pathway involving GABA transaminase, gamma-hydroxybutyric acid (GHB) can also be metabolized to SSA via GHB dehydrogenase or by GHB transhydrogenase (D-2-hydroxyglutarate transhydrogenase).

References

References

  1. (2014-12-20). "Activation of gab cluster transcription in Bacillus thuringiensis by γ-aminobutyric acid or succinic semialdehyde is mediated by the Sigma 54-dependent transcriptional activator GabR". BMC Microbiology.
  2. (December 2005). "Determination of the GABA analogue succinic semialdehyde in urine and cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid chromatography–tandem mass spectrometry: Application to SSADH deficiency". Journal of Inherited Metabolic Disease.
  3. (January 2015). "GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome". Current Neuropharmacology.
  4. (January 2021). "γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology". The AAPS Journal.
  5. (May 2020). "Kinetics aspects of Gamma-hydroxybutyrate dehydrogenase". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics.
  6. (March 2016). "The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review". Neuropsychobiology.
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aldehydes carboxylic-acids gamma-hydroxybutyric-acid aldehydic-acids
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