GABA metabolism (aka GHB) (Homo sapiens)

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1, 3111, 2SSADH4-butyrolactone3,4-dihydroxybutyric acidADHTCA cyclesuccinic acidD-2-hydroxyglutarate transhydrogenaseglycolic acid4-hydroxybutyraldehydeGABATlactamaseSerum paraoxonase/lactonase 3 (b)succinic semialdehyde ALDHSerum paraoxonase/lactonase 3 (a)gamma-aminobutanoic acid (GABA)1,4-butanediol Serum paraoxonase/lactonase 3 (c) alpha-ketoglutarateGHB dehydrogenasefatty acid beta-oxidation spiralgamma-hydroxybutyric acid (GHB)SSA reductase3-oxo-4-hydroxybutyric acidD-2-hydroxyglutaric acid33ADHSSADHglutamine33succinic semialdehyde 3glutamic acid33GABAT33uracil3beta-alanine3malonic semialdehyde333334,5-dihydroxyhexanoic acidGABAT34-hydroxybutyric acid333-oxo-4-hydroxybutanoic32-oxo-4-hydroxybutanoic3-hydroxypropionic333332-ketoglutarateD-2-hydroxyglutarate3333DiseaseCatalysisPathwayStimulationProteinMetaboliteConversionConnection to diseaseLegendSerum paraoxonase/lactonase 3


Description

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 Chapter 5 of the book of Blau (ISBN 3642403360 (978-3642403361)), Fig. 5.3.

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Ontology Terms

 

Bibliography

  1. Hyun-U Cho, Sunpil Kim, Jeongeun Sim, Seulkee Yang, Heeyoung An, Min-Ho Nam, Dong-Pyo Jang, C Justin Lee; ''Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis''; Exp Mol Med., 2021 PubMed Europe PMC Scholia
  2. Struys EA, Verhoeven NM, Ten Brink HJ, Wickenhagen WV, Gibson KM, Jakobs C; ''Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias.''; J Inherit Metab Dis, 2005 PubMed Europe PMC Scholia
  3. G K Brown, C H Cromby, N J Manning, R J Pollitt; ''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''; J Inherit Metab Dis ., 1987 PubMed Europe PMC Scholia
  4. Nenad Blau, Carlo Dionisi Vici, K Michael Gibson, Marinus Duran; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; Springer (ISBN-13: 9783642403361), 2014
  5. Struys EA, Verhoeven NM, Jansen EE, Ten Brink HJ, Gupta M, Burlingame TG, Quang LS, Maher T, Rinaldo P, Snead OC, Goodwin AK, Weerts EM, Brown PR, Murphy TC, Picklo MJ, Jakobs C, Gibson KM; ''Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase.''; Metabolism, 2006 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128244view23:39, 29 January 2024EweitzSoften disease, standardize case
128243view23:33, 29 January 2024EweitzOntology Term : 'astrocyte' added !
126055view13:39, 31 March 2023DeSlReannotated ADH with Enzyme nomenclature iso Wikidata
126054view13:35, 31 March 2023DeSlConnected unconnected line
124222view08:57, 3 October 2022DeSlUpdated layout of Disease Nodes
123770view13:48, 12 August 2022EgonwCorrect data sources
123730view15:14, 11 August 2022DeSlUpdate ADH ID to EC code
123729view15:11, 11 August 2022DeSlAdded details on astrocyte conversion to GABA
123728view14:54, 11 August 2022DeSlOntology Term : 'gamma-amino butyric acid metabolism disorder' added !
123727view14:53, 11 August 2022DeSlOntology Term : 'GABA aminotransferase deficiency' added !
123726view14:51, 11 August 2022DeSlUpdate legend
123722view14:39, 11 August 2022DeSlAdded 4,5-dihydroxyhexanoic acid lactone
123720view14:34, 11 August 2022DeSlUpdating visualization, added proteins from glutamine to GABA conversion
123713view14:07, 11 August 2022DeSlUpdated description to Ed. 5
120415view09:35, 30 November 2021Fehrhartboxed pathway node
119999view08:02, 9 October 2021EgonwNot conversions
119991view06:47, 8 October 2021EgonwMade two pathways clickable
119990view06:46, 8 October 2021EgonwNot conversions
119569view11:09, 17 July 2021YasminomarAdded the disease “GABAT” to the second reaction catabolized by GABAT
119509view13:20, 6 July 2021YasminomarAligned nodes
119507view09:36, 6 July 2021YasminomarUpdated ID for succinic acid
119506view09:15, 6 July 2021YasminomarAdded Rhea-ID for GHB dehydrogenase
119495view14:38, 4 July 2021YasminomarUpdated some metabolite IDs and added Rhea-ID for SSADH
119289view11:02, 23 June 2021FinterlyAdded ISBN for book citation
116270view09:35, 23 April 2021YasminomarAdded a reference + side reaction (reduction of 2-KG to D-2-HG) catalyzed by D-2-HG transhydrogenase
116267view22:34, 22 April 2021YasminomarChanged IDs for Serum paraoxonase/lactonase 3, lactamase, d-2-hydroxyglutarate transhydrogenase, GHB dehydrogenase to Uniprot-TrEMBL IDs
116245view20:12, 21 April 2021YasminomarChanged the shape type of some metabolites from rectangle to rounded rectangle, updated GABAT interactions and changed ID for GABA
116219view21:25, 20 April 2021YasminomarChanged ID for SSA reductase and added Rhea-interaction
116218view21:02, 20 April 2021YasminomarAdded Rhea for the reaction catalyzed by d-2-hydroxyglutarate transhydrogenase, changed IDs for gamma-hydroxybutanoic acid (GHB) and succinic semialdehyde
116217view20:46, 20 April 2021YasminomarAdded IDs for uracil, beta-alanine, malonic semialdehyde, GABAT, glutamine, glutamic acid
116216view20:30, 20 April 2021YasminomarAdded IDs for D-2-hydroxyglutarate, 2-ketoglutarate, 4-hydroxybutyric acid, 3-oxo-4-hydroxybutanoic, 2-oxo-4-hydroxybutanoic, 3-hydroxypropionic
114138view10:42, 23 December 2020DeSlUpdated description with fig. number.
114137view10:41, 23 December 2020DeSlAdded legend, converted interaction to disease to graphical lines.
114048view12:12, 18 December 2020DeSlUpdated PW with additonal metabolites
114047view12:05, 18 December 2020DeSlAdded additional disease, including OMIM links
114045view11:42, 18 December 2020DeSlAdded book ref to description
114044view11:41, 18 December 2020DeSlAdded lit. ref of Blau to specific sections
114043view11:36, 18 December 2020DeSlUpdating pathway with information from chapter 5, ed. 4 of Blau book.
113892view03:33, 7 December 2020EgonwMarked a datanode as disease
102675view09:15, 17 January 2019DeSlModified description
102674view09:13, 17 January 2019DeSlChanged weird characters in comment of 4-hydroxybutaldehyde
102673view09:10, 17 January 2019DeSlChanged layout of disease node
94898view13:55, 12 October 2017DeSlModified description
94882view10:05, 11 October 2017DeSlOntology Term : 'gamma-aminobutyric acid metabolic pathway' added !
94881view10:04, 11 October 2017DeSlOntology Term : 'succinic semialdehyde dehydrogenase deficiency' added !
94880view10:04, 11 October 2017DeSlOntology Term : 'neurotransmitter metabolic pathway' added !
94879view10:03, 11 October 2017DeSlAdded wikidata as database source where applicable
94878view10:02, 11 October 2017DeSlAdded ID for succinic semialdehyde, removed unused metabolite node.
94877view10:00, 11 October 2017DeSlAdded wikidata as database source where applicable
94876view09:58, 11 October 2017DeSlAdded literature ref, added content to the PW from this ref.

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,4-butanediol MetaboliteCHEBI:41189 (ChEBI)
2-ketoglutarateMetaboliteCHEBI:16810 (ChEBI)
2-oxo-4-hydroxybutanoicMetaboliteCHEBI:173437 (ChEBI) aka 2-oxo-4-hydroxybutyric acid aka 4-hydroxy-2-oxobutanoic acid
3,4-dihydroxybutyric acidMetaboliteCHEBI:86371 (ChEBI)
3-hydroxypropionicMetaboliteCHEBI:33404 (ChEBI) aka 3-hydroxypropionic acid
3-oxo-4-hydroxybutanoicMetabolite19793911 (PubChem-compound) aka 3-oxo-4-hydroxybutyric acid aka 4-hydroxy-3-oxobutanoic acid
3-oxo-4-hydroxybutyric acidMetabolite19793911 (PubChem-compound) aka 4-hydroxy-3-oxobutanoic acid
4,5-dihydroxyhexanoic acidMetaboliteHMDB0240745 (HMDB)
4-butyrolactoneMetaboliteCHEBI:42639 (ChEBI)
4-hydroxybutyraldehydeMetabolite93093 (PubChem-compound) aka 4-hydroxybutanal
4-hydroxybutyric acidMetaboliteCHEBI:30830 (ChEBI)
ADHProteinQ410754 (Wikidata) alcohol dehydrogenase
ALDHProtein1.2.1.3 (Enzyme Nomenclature) aldehyde dehydrogenase
D-2-hydroxyglutarate transhydrogenaseProteinQ8IWW8 (Uniprot-TrEMBL) aka hydroxyacid-oxoacid transhydrogenase (HOT)
D-2-hydroxyglutarateMetaboliteCHEBI:15801 (ChEBI) D-2-hydroxyglutaric acid
D-2-hydroxyglutaric acidMetaboliteCHEBI:15801 (ChEBI) aka D-2-hydroxyglutarate
GABATProteinP80404 (Uniprot-TrEMBL) GABA transaminase
GHB dehydrogenaseProtein1.1.1.61 (Enzyme Nomenclature) aka NAD-dependent 4-hydroxybutyrate dehydrogenase
SSA reductaseProteinO43488 (Uniprot-TrEMBL)
SSADHProteinP51649 (Uniprot-TrEMBL) Succinate-semialdehyde dehydrogenase
Serum paraoxonase/lactonase 3 (a)Protein3.1.8.1 (Enzyme Nomenclature)
Serum paraoxonase/lactonase 3 (b)Protein3.1.1.81 (Enzyme Nomenclature)
Serum paraoxonase/lactonase 3 (c) Protein3.1.1.2 (Enzyme Nomenclature)
Serum paraoxonase/lactonase 3ProteinQ15166 (Uniprot-TrEMBL)
TCA cyclePathwayWP78 (WikiPathways) aka Krebs Cycle
alpha-ketoglutarateMetaboliteCHEBI:16810 (ChEBI) aka 2-ketoglutarate aka 2-oxoglutarate
beta-alanineMetaboliteCHEBI:16958 (ChEBI)
fatty acid beta-oxidation spiralPathwayWP143 (WikiPathways)
gamma-aminobutanoic acid (GABA)MetaboliteCHEBI:59888 (ChEBI) aka gamma-aminobutyric acid
gamma-hydroxybutyric acid (GHB)MetaboliteCHEBI:16724 (ChEBI) aka 4-hydroxybutanoic acid
glutamic acidMetaboliteCHEBI:16015 (ChEBI)
glutamineMetaboliteCHEBI:28300 (ChEBI)
glycolic acidMetaboliteCHEBI:17497 (ChEBI)
lactamaseProteinP16444 (Uniprot-TrEMBL)
malonic semialdehydeMetaboliteCHEBI:17960 (ChEBI)
succinic acidMetaboliteCHEBI:15741 (ChEBI) aka succinate
succinic semialdehyde MetaboliteCHEBI:57706 (ChEBI)
uracilMetaboliteCHEBI:17568 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
4-butyrolactonegamma-hydroxybutyric acid (GHB)mim-conversion20402 (Rhea) parent compounds, not a specific reaction
D-2-hydroxyglutaric acidmim-conversion24735 (Rhea)
alpha-ketoglutaratemim-conversion24735 (Rhea)
gamma-aminobutanoic acid (GABA)succinic semialdehyde mim-conversion23353 (Rhea)
gamma-hydroxybutyric acid (GHB)mim-conversion24735 (Rhea)
gamma-hydroxybutyric acid (GHB)succinic semialdehyde mim-conversion23949 (Rhea)
succinic semialdehyde gamma-hydroxybutyric acid (GHB)mim-conversion26383 (Rhea)
succinic semialdehyde succinic acidmim-conversion13218 (Rhea)
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