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 http://www.drugbank.ca/drugs/DB00313
Metabolic pathway from: http://smpdb.ca/view/SMP00635
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3871 CPTAC Assay Portal].e87e66bb2e2cc6bb78f67cd4f5bf1ac49epilepsyDOID:1826Human Disease Ontologyxenobiotic metabolic pathwayPW:0001229Pathway OntologyneuronCL:0000540Cell Ontologyvalproic acid drug pathwayPW:0001451Pathway OntologyhepatocyteCL:0000182Cell Ontology8168173PubMedMetabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes.Chem Biol Interact1994Kassahun KHu PGrillo MPDavis MRJin LBaillie TA1676665PubMedIdentification 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 Dispos1991Kassahun KFarrell KAbbott F21843514PubMedValproic acid utilizes the isoleucine breakdown pathway for its complete β-oxidation.Biochem Pharmacol2011LuÃs PBRuiter JPOfman RIjlst LMoedas MDiogo LGarcia Pde Almeida ITDuran MWanders RJSilva MF1988037PubMedMitochondrial metabolism of valproic acid.Biochemistry1991Li JNorwood DLMao LFSchulz H2112956PubMedThe 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 Acta1990Ito MIkeda YArnez JGFinocchiaro GTanaka K14597963PubMedInfluence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes.Pharmacogenomics J2003Ho PCAbbott FSZanger UMChang TK16945988PubMedContribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype.Toxicol Sci2006Kiang TKHo PCAnari MRTong VAbbott FSChang TK9353388PubMedHuman CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid.J Pharmacol Exp Ther1997Sadeque AJFisher MBKorzekwa KRGonzalez FJRettie AE17687269PubMedPharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.Clin Pharmacol Ther2008Chung JYCho JYYu KSKim JRLim KSSohn DRShin SGJang IJ18838507PubMedEffect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10.Drug Metab Dispos2009Argikar UARemmel RP15761113PubMed