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).
Authors
Denise Slenter , Egon Willighagen , Yasmin Omar , Finterly Hu , Friederike Ehrhart , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Rare DiseasesAnnotations
Disease Ontology
GABA aminotransferase deficiency gamma-amino butyric acid metabolism disorder succinic semialdehyde dehydrogenase deficiencyPathway Ontology
gamma-aminobutyric acid metabolic pathway neurotransmitter metabolic pathway xenobiotic metabolic pathwayCell Type Ontology
astrocyte| 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 |
| GAD | Protein | eccode:4.1.1.15 | 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:3.5.1.2 | 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:1.1.1.1 | alcohol dehydrogenase; Wikidata:Q410754 |
| Serum paraoxonase/lactonase 3 (b) | Protein | eccode:3.1.1.81 | |
| GHB dehydro-genase | Protein | eccode:1.1.1.61 | aka NAD-dependent 4-hydroxybutyrate dehydrogenase |
| MAOB | Protein | uniprot:P27338 | |
| ALDH | Protein | eccode:1.2.1.3 | aldehyde dehydrogenase |
| SSA reductase | Protein | uniprot:O43488 | |
| GABAT | Protein | uniprot:P80404 | GABA transaminase |
| Serum paraoxonase/lactonase 3 (c) | Protein | eccode:3.1.1.2 | |
| GAD1 | Protein | uniprot:Q99259 | AKA GAD67 |
| Lactamase | Protein | uniprot:P16444 | |
| GLS (kidney) | Protein | uniprot:O94925 | |
| Homocarnosinase/carnosinase | Protein | eccode:3.4.13.3 | |
| Serum paraoxonase/lactonase 3 (a) | Protein | eccode:3.1.8.1 | |
| SSADH | Protein | uniprot:P51649 | Succinate-semialdehyde dehydrogenase |
| Serum paraoxonase/lactonase 3 | Protein | uniprot:Q15166 | |
| GLS2 (liver) | Protein | uniprot:Q9UI32 | |
| GAD2 | Protein | uniprot:Q05329 | AKA GAD65 |
References
- 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: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
- 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
- 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
- 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
- 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