Valproic acid pathway (Homo sapiens)

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1-11re-uptake of GABAmode of actionmetabolismincreased levelsValproic acidCYP2C9ABATIVDGABA5-Hydroxyvalproic acidPropionyl-CoAHADHBACSM12-ene-Valproic acid CoA2-n-Propyl-4-oxopentanoic acidCYP2B6Pentanoyl-CoA3-ene-Valproic acid CoA4-ene-Valproic acid3-ene-Valproic acid CoA2,3-diene-Valproic acid-CoAValproic acid CoA3-oxo-Valproic acid CoA4-Hydroxyvalproic acidHDAC14-ene-Valproic acid CoAUridine diphosphate glucuronic acidEHHADHValproic acid glucuronideHSD17B102,3-diene-Valproic acid-CoAACADSBCYP2A63-Hydroxyvalproic acid CoA2-Propyl-2,4-pentadienoic acid3-Oxovalproic acidUridine 5'-diphosphateUGT1A3HADHA2-Propylglutaric acid3-Hydroxyvalproic acidACADSBCYP2A6CYP2B6CYP2C9CYP2A6


Description

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Bibliography

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  1. Li J, Norwood DL, Mao LF, Schulz H; ''Mitochondrial metabolism of valproic acid.''; Biochemistry, 1991 PubMed Europe PMC Scholia
  2. Ho PC, Abbott FS, Zanger UM, Chang TK; ''Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes.''; Pharmacogenomics J, 2003 PubMed Europe PMC Scholia
  3. Ito M, Ikeda Y, Arnez JG, Finocchiaro G, Tanaka K; ''The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl-CoA dehydrogenase.''; Biochim Biophys Acta, 1990 PubMed Europe PMC Scholia
  4. Chung JY, Cho JY, Yu KS, Kim JR, Lim KS, Sohn DR, Shin SG, Jang IJ; ''Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.''; Clin Pharmacol Ther, 2008 PubMed Europe PMC Scholia
  5. Kiang TK, Ho PC, Anari MR, Tong V, Abbott FS, Chang TK; ''Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype.''; Toxicol Sci, 2006 PubMed Europe PMC Scholia
  6. Sadeque AJ, Fisher MB, Korzekwa KR, Gonzalez FJ, Rettie AE; ''Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid.''; J Pharmacol Exp Ther, 1997 PubMed Europe PMC Scholia
  7. Argikar UA, Remmel RP; ''Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10.''; Drug Metab Dispos, 2009 PubMed Europe PMC Scholia
  8. Kassahun K, Hu P, Grillo MP, Davis MR, Jin L, Baillie TA; ''Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes.''; Chem Biol Interact, 1994 PubMed Europe PMC Scholia
  9. Kassahun K, Farrell K, Abbott F; ''Identification and characterization of the glutathione and N-acetylcysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans.''; Drug Metab Dispos, 1991 PubMed Europe PMC Scholia
  10. ''''; , PubMed Europe PMC Scholia
  11. Luís PB, Ruiter JP, Ofman R, Ijlst L, Moedas M, Diogo L, Garcia P, de Almeida IT, Duran M, Wanders RJ, Silva MF; ''Valproic acid utilizes the isoleucine breakdown pathway for its complete β-oxidation.''; Biochem Pharmacol, 2011 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
106754view13:23, 17 September 2019MaintBotHMDB identifier normalization
105851view23:16, 15 August 2019KhanspersModified description
94406view15:25, 6 September 2017DeSlOntology Term : 'xenobiotic metabolic pathway' added !
88572view09:53, 11 August 2016Fehrhartfixed weird lines
88571view09:50, 11 August 2016FehrhartModified description
88570view09:49, 11 August 2016FehrhartModified description
88569view09:49, 11 August 2016FehrhartModified description
88568view09:48, 11 August 2016FehrhartModified description
88567view09:47, 11 August 2016FehrhartModified description
88565view09:40, 11 August 2016FehrhartModified description
88564view09:32, 11 August 2016FehrhartOntology Term : 'epilepsy' added !
88563view09:32, 11 August 2016FehrhartOntology Term : 'hepatocyte' added !
88562view09:32, 11 August 2016FehrhartOntology Term : 'neuron' added !
88561view09:31, 11 August 2016FehrhartOntology Term : 'valproic acid drug pathway' added !
88560view09:31, 11 August 2016FehrhartModified description
88559view09:30, 11 August 2016FehrhartNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2,3-diene-Valproic acid-CoAMetaboliteHMDB60723 (HMDB)
2-Propyl-2,4-pentadienoic acidMetaboliteHMDB60682 (HMDB)
2-Propylglutaric acidMetaboliteHMDB60684 (HMDB)
2-ene-Valproic acid CoAMetaboliteHMDB60714 (HMDB)
2-n-Propyl-4-oxopentanoic acidMetaboliteHMDB60683 (HMDB)
3-Hydroxyvalproic acid CoAMetaboliteHMDB60744 (HMDB)
3-Hydroxyvalproic acidMetaboliteHMDB13899 (HMDB)
3-Oxovalproic acidMetaboliteHMDB60685 (HMDB)
3-ene-Valproic acid CoAMetaboliteHMDB60740 (HMDB)
3-oxo-Valproic acid CoAMetaboliteHMDB60749 (HMDB)
4-Hydroxyvalproic acidMetaboliteHMDB13900 (HMDB)
4-ene-Valproic acid CoAMetaboliteHMDB60762 (HMDB)
4-ene-Valproic acidMetaboliteHMDB13897 (HMDB)
5-Hydroxyvalproic acidMetaboliteHMDB13898 (HMDB)
ABATGeneProductENSG00000183044 (Ensembl)
ACADSBGeneProductENSG00000196177 (Ensembl)
ACSM1GeneProductENSG00000166743 (Ensembl)
CYP2A6GeneProductENSG00000255974 (Ensembl)
CYP2B6GeneProductENSG00000197408 (Ensembl)
CYP2C9GeneProductENSG00000138109 (Ensembl)
EHHADHGeneProductENSG00000113790 (Ensembl)
GABAMetaboliteHMDB00112 (HMDB)
HADHAGeneProductENSG00000084754 (Ensembl)
HADHBGeneProductENSG00000138029 (Ensembl)
HDAC1GeneProductENSG00000116478 (Ensembl)
HSD17B10GeneProductENSG00000072506 (Ensembl)
IVDGeneProductENSG00000128928 (Ensembl)
Pentanoyl-CoAMetaboliteHMDB13037 (HMDB)
Propionyl-CoAMetaboliteHMDB01275 (HMDB)
UGT1A3GeneProductENSG00000243135 (Ensembl)
Uridine 5'-diphosphateMetaboliteHMDB00295 (HMDB)
Uridine diphosphate glucuronic acidMetaboliteHMDB00935 (HMDB)
Valproic acid CoAMetaboliteHMDB60877 (HMDB)
Valproic acid glucuronideMetaboliteHMDB00901 (HMDB)
Valproic acidMetaboliteHMDB01877 (HMDB)

Annotated Interactions

No annotated interactions

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