Valproic acid pathway (Homo sapiens)

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1-11re-uptake of GABAmode of actionincreased levelsmetabolismABATValproic acidACADSB3-ene-Valproic acid CoA5-Hydroxyvalproic acid4-Hydroxyvalproic acid4-ene-Valproic acid CoAPentanoyl-CoA2-Propylglutaric acidValproic acid CoA2-n-Propyl-4-oxopentanoic acid4-ene-Valproic acid3-Oxovalproic acid3-Hydroxyvalproic acid2-ene-Valproic acid CoA3-ene-Valproic acid CoACYP2B6HADHB2,3-diene-Valproic acid-CoACYP2C93-oxo-Valproic acid CoAUGT1A3HADHA2,3-diene-Valproic acid-CoAHSD17B10Uridine 5'-diphosphateUridine diphosphate glucuronic acidPropionyl-CoA2-Propyl-2,4-pentadienoic acidACSM1EHHADHValproic acid glucuronideCYP2A6GABAHDAC1IVD3-Hydroxyvalproic acid CoAACADSBCYP2A6CYP2B6CYP2C9CYP2A6


Valproic acid is a drug used for treatment and management of seizure disorders, mania and prophylactic treatment of migraine headache. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome.

Valproic Acid dissociates to the valproate ion in the gastrointestinal tract and then binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection. Source: description from

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  1. 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
  2. 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
  3. 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
  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
  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
  6. 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
  7. 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
  8. 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
  9. 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
  10. ''''; , PubMed
  11. Li J, Norwood DL, Mao LF, Schulz H; ''Mitochondrial metabolism of valproic acid.''; Biochemistry, 1991 PubMed


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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


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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

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