GABA metabolism (aka GHB) (WP4157)

Homo sapiens

Gamma-Hydroxybutyric acid (GHB) is a naturally occurring neurotransmitter and a psychoactive drug. This compound is a precursor to GABA, glutamate, and glycine in certain brain areas, acts on the GHB receptor and is a weak agonist at the GABAB receptor. GHB has been used in a medical setting as a general anesthetic and as a treatment for cataplexy, narcolepsy, and alcoholism. It is also used illegally as an intoxicant, to try to increase athletic performance, and as a date rape drug. GHB is also produced as a result of fermentation, and is found in small quantities in some beers and wines, beef and small citrus fruits. Succinic semialdehyde dehydrogenase deficiency is a disease that causes GHB to accumulate in the blood. Part of this pathway was inspired by Edition 5, Chapter 24 (Fig.24.2) of the book of Blau (ISBN 9783030677268) (Ed.4 Chapter 5, Fig. 5.3).


Denise Slenter , Egon Willighagen , Yasmin Omar , Finterly Hu , Friederike Ehrhart , and Eric Weitz


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Disease Ontology

GABA aminotransferase deficiency gamma-amino butyric acid metabolism disorder succinic semialdehyde dehydrogenase deficiency

Pathway Ontology

gamma-aminobutyric acid metabolic pathway neurotransmitter metabolic pathway xenobiotic metabolic pathway

Cell Type Ontology



Label Type Compact URI Comment
Gamma-aminobutanoic acid (GABA) Metabolite chebi:59888 aka gamma-aminobutyric acid
succinic acid Metabolite chebi:30031 aka succinate
N-acetylputrescine Metabolite chebi:17768
4,5-dihydroxyhexanoic acid lactone Metabolite hmdb:HMDB0002173 AKA Solerol, ring-structure, appears to ba a biomarker for SSADH deficiency [PMID:3126356]
4-butyrolactone Metabolite chebi:42639
D-2-hydroxyglutaric acid Metabolite chebi:15801 aka D-2-hydroxyglutarate
Gamma-hydroxybutyric acid (GHB) Metabolite chebi:16724 aka 4-hydroxybutanoic acid, Gamma-Hydroxybutyrate
Homocarnosine Metabolite chebi:85981
1,4-butanediol Metabolite chebi:41189
N-acetyl gamma-aminobutyraldehyde Metabolite pubchem.compound:440850 AKA 4-Acetamidobutanal
3-oxo-4-hydroxybutyric acid Metabolite pubchem.compound:19793911 aka 4-hydroxy-3-oxobutanoic acid
N-acetyl gamma-aminobutyrate Metabolite pubchem.compound:18189 AKA 4-Acetamidobutyric acid
4-hydroxybutyraldehyde Metabolite pubchem.compound:93093 aka 4-hydroxybutanal
Putrescine Metabolite chebi:17148
Alpha-ketoglutarate Metabolite chebi:16810 aka 2-ketoglutarate aka 2-oxoglutarate
Glycolic acid Metabolite chebi:17497
3,4-dihydroxybutyric acid Metabolite chebi:86371
PLP Metabolite chebi:18405 AKA Pyridoxal phosphate, pyridoxal 5'-phosphate, P5P
Glutamine Metabolite chebi:28300
Succinic semialdehyde Metabolite chebi:57706
Glutamic acid Metabolite chebi:16015 AKA glutamate
Uracil Metabolite chebi:17568
Beta-alanine Metabolite chebi:16958
Malonic semialdehyde Metabolite chebi:17960
4,5-dihydroxyhexanoic acid Metabolite hmdb:HMDB0240745 AKA DHHA, open-structure, appears to ba a biomarker for SSADH deficiency [PMID:3126356]
4-hydroxybutyric acid Metabolite chebi:30830
3-oxo-4-hydroxybutanoic Metabolite pubchem.compound:19793911 aka 3-oxo-4-hydroxybutyric acid aka 4-hydroxy-3-oxobutanoic acid
2-oxo-4-hydroxybutanoic Metabolite chebi:173437 aka 2-oxo-4-hydroxybutyric acid aka 4-hydroxy-2-oxobutanoic acid
3-hydroxypropionic Metabolite chebi:33404 aka 3-hydroxypropionic acid
2-ketoglutarate Metabolite chebi:16810
D-2-hydroxyglutarate Metabolite chebi:15801 D-2-hydroxyglutaric acid
PLP Metabolite chebi:18405 AKA Pyridoxal phosphate, pyridoxal 5'-phosphate, P5P
GAD Protein eccode: AKA Glutamic acid decarboxylase, exists in two isoforms with molecular weights of 67 and 65 kDa (GAD67 and GAD65), encoded by two different genes (GAD1 and GAD2)
D-2-hydroxyglutarate transhydrogenase Protein uniprot:Q8IWW8 aka hydroxyacid-oxoacid transhydrogenase (HOT)
Glutaminase Protein eccode: Glutaminase has tissue-specific isoenzymes and 4 isoforms: the GLS gene encodes 2 types (active in kidney, and the GLS2 gene encodes 2 forms (active in liver)
ADH Protein eccode: alcohol dehydrogenase; Wikidata:Q410754
Serum paraoxonase/lactonase 3 (b) Protein eccode:
GHB dehydro-genase Protein eccode: aka NAD-dependent 4-hydroxybutyrate dehydrogenase
MAOB Protein uniprot:P27338
ALDH Protein eccode: aldehyde dehydrogenase
SSA reductase Protein uniprot:O43488
GABAT Protein uniprot:P80404 GABA transaminase
Serum paraoxonase/lactonase 3 (c) Protein eccode:
GAD1 Protein uniprot:Q99259 AKA GAD67
Lactamase Protein uniprot:P16444
GLS (kidney) Protein uniprot:O94925
Homocarnosinase/carnosinase Protein eccode:
Serum paraoxonase/lactonase 3 (a) Protein eccode:
ADH Protein eccode: alcohol dehydrogenase; Wikidata:Q410754
SSADH Protein uniprot:P51649 Succinate-semialdehyde dehydrogenase
GABAT Protein uniprot:P80404 GABA transaminase
Serum paraoxonase/lactonase 3 Protein uniprot:Q15166
GLS2 (liver) Protein uniprot:Q9UI32
GAD2 Protein uniprot:Q05329 AKA GAD65
ALDH Protein eccode: aldehyde dehydrogenase


  1. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: OpenLibrary Worldcat
  2. Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. Brown GK, Cromby CH, Manning NJ, Pollitt RJ. J Inherit Metab Dis. 1987;10(4):367–75. PubMed Europe PMC Scholia
  3. Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. Struys EA, Verhoeven NM, Ten Brink HJ, Wickenhagen WV, Gibson KM, Jakobs C. J Inherit Metab Dis. 2005;28(6):921–30. PubMed Europe PMC Scholia
  4. Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase. Struys EA, Verhoeven NM, Jansen EEW, Ten Brink HJ, Gupta M, Burlingame TG, et al. Metabolism. 2006 Mar;55(3):353–8. PubMed Europe PMC Scholia
  5. Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis. Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, et al. Exp Mol Med. 2021 Jul;53(7):1148–58. PubMed Europe PMC Scholia