You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2006-02-24 11:11:14 UTC
Update Date2016-02-11 01:05:03 UTC
HMDB IDHMDB01877
Secondary Accession NumbersNone
Metabolite Identification
Common NameValproic acid
DescriptionValproic acid (VPA) is considered to be a drug of first choice and one of the most frequently-prescribed antiepileptic drugs worldwide for the therapy of generalized and focal epilepsies, including special epileptic. It is a broad-spectrum antiepileptic drug and is usually well tolerated. Rarely, serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulopathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy, but there is still a lack of knowledge about the incidence and occurrence of these special side effects. VPA has been approved for stabilization of manic episodes in patients with bipolar disorder. It is also used to treat migraine headaches and schizophrenia. As the use of VPA increases, the number of both accidental and intentional exposures increases. This is paralleled by more reports of VPA-induced toxicity. VPA is relatively contraindicated in pregnancy due to its teratogenicity. It is a known folate antagonist, which can cause neural tube defects. Thus, folic acid supplements may alleviate teratogenic problems. Women who become pregnant whilst taking valproate should be counselled as to its risks. VPA is an inhibitor of the enzyme histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. Patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a median 75% reduction in latent HIV infection. VPA is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Valproic Acid dissociates to the valproate ion in the gastrointestinal tract. (PMID: 18201150 , 17496767 ).
Structure
Thumb
Synonyms
ValueSource
2-N-Propyl-N-valeric acidChEBI
2-PROPYL-pentanoIC ACIDChEBI
2-Propylpentanoic acidChEBI
2-Propylvaleric acidChEBI
4-Heptanecarboxylic acidChEBI
Acide valproiqueChEBI
acido ValproicoChEBI
Acidum valproicumChEBI
DepakeneChEBI
Di-N-propylacetic acidChEBI
Di-N-propylessigsaeureChEBI
Dipropylacetic acidChEBI
DPAChEBI
N-DPAChEBI
ValproinsaeureChEBI
VPAChEBI
2-N-Propyl-N-valerateGenerator
ValproateGenerator
2-PROPYL-pentanoateGenerator
2-PropylpentanoateGenerator
2-PropylvalerateGenerator
4-HeptanecarboxylateGenerator
Di-N-propylacetateGenerator
DipropylacetateGenerator
(N-C3H7)2chcoohHMDB
(S)-2-Propyl-4-pentanoateHMDB
(S)-2-Propyl-4-pentanoic acidHMDB
Alti-valproicHMDB
apo-DivalproexHMDB
apo-ValproicHMDB
apo-Valproic syrupHMDB
AvuganeHMDB
BacecaHMDB
ConvulexHMDB
DelepsineHMDB
DepakinHMDB
Depakin chronoHMDB
DepakineHMDB
Depakine chronoHMDB
DeproicHMDB
Di-N-propylessigsaureHMDB
DivalproexHMDB
DOM-divalproexHMDB
Dom-valproateHMDB
DOM-valproicHMDB
Dom-valproic acidHMDB
DOM-valproic acid e.c.HMDB
Dom-valproic acid syrupHMDB
Epiject i.v.HMDB
EpilexHMDB
EpilimHMDB
EpivalHMDB
Epival erHMDB
ErgenylHMDB
Gen-divalproexHMDB
Kyselina 2-propylvalerovaHMDB
Med valproicHMDB
MylproinHMDB
MyproateHMDB
Myproic acidHMDB
N-Dipropylacetic acidHMDB
novo-DivalproexHMDB
novo-ValproicHMDB
novo-Valproic - eccHMDB
novo-Valproic soft gel capHMDB
Nu-valproicHMDB
PEACHMDB
Penta-valproicHMDB
PHL-ValproateHMDB
PHL-Valproic acidHMDB
PHL-Valproic acid e.c.HMDB
PMS-DivalproexHMDB
PMS-ValproateHMDB
PMS-Valproic acidHMDB
PMS-Valproic acid e.c.HMDB
Propylvaleric acidHMDB
ratio-Valproic - eccHMDB
S(-)-4-En-valproateHMDB
S(-)-4-En-valproic acidHMDB
S-2-N-Propyl-4-pentenoateHMDB
S-2-N-Propyl-4-pentenoic acidHMDB
Sandoz valproicHMDB
SavicolHMDB
SprinkleHMDB
ValcoteHMDB
ValparinHMDB
Valproic acid uspHMDB
Chemical FormulaC8H16O2
Average Molecular Weight144.2114
Monoisotopic Molecular Weight144.115029756
IUPAC Name2-propylpentanoic acid
Traditional Namevalproic acid
CAS Registry Number99-66-1
SMILES
CCCC(CCC)C(O)=O
InChI Identifier
InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)
InChI KeyInChIKey=NIJJYAXOARWZEE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as methyl-branched fatty acids. These are fatty acids with an acyl chain that has a methyl branch. Usually, they are saturated and contain only one or more methyl group. However, branches other than methyl may be present.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMethyl-branched fatty acids
Alternative Parents
Substituents
  • Methyl-branched fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling Point222 °CNot Available
Water Solubility2 mg/mL at 20 °CNot Available
LogP2.75SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility2.36 mg/mLALOGPS
logP2.54ALOGPS
logP2.8ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)5.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity40.25 m3·mol-1ChemAxon
Polarizability17 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0udi-2900000000-156413e81733a6236c1fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-0f6y-2900000000-a769cafb885b78532cacView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-0gbj-7900000000-46a522b9a26459334f5aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0006-0900000000-39a45d4e3201082d9d89View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0002-9000000000-4ddd957d8c8dc2b1de03View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0006-0900000000-6ba582ae102c4721034dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0006-0900000000-58d9ba88010f1b370c58View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0006-3900000000-2d1032d7e8ac58235b4fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a4j-9000000000-0d39870bc4521a42c50aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-00di-9000000000-3c4e21b69b8877d6df3eView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0fk9-9300000000-1a0314ea63d5a3c9bba1View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Brain
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Valproic Acid Metabolism PathwaySMP00635Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified208.0 (3.5-416.0) uMAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022722
KNApSAcK IDNot Available
Chemspider ID3009
KEGG Compound IDC07185
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkValproic acid
NuGOwiki LinkHMDB01877
Metagene LinkHMDB01877
METLIN ID2986
PubChem Compound3121
PDB ID2PP
ChEBI ID39867
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Nemeroff CB: The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. 2003;37(4):133-46. [15131523 ]
  2. Bell EC, Willson MC, Wilman AH, Dave S, Silverstone PH: Differential effects of chronic lithium and valproate on brain activation in healthy volunteers. Hum Psychopharmacol. 2005 Aug;20(6):415-24. [16106488 ]
  3. Sztajnkrycer MD: Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol. 2002;40(6):789-801. [12475192 ]
  4. Seyfert S, Bernarding J, Braun J: Volume-selective 1H MR spectroscopy for in vivo detection of valproate in patients with epilepsy. Neuroradiology. 2003 May;45(5):295-9. Epub 2003 Mar 27. [12669157 ]
  5. Eyal S, Lamb JG, Smith-Yockman M, Yagen B, Fibach E, Altschuler Y, White HS, Bialer M: The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver. Br J Pharmacol. 2006 Oct;149(3):250-60. Epub 2006 Aug 7. [16894351 ]
  6. Loscher W: Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs. 2002;16(10):669-94. [12269861 ]
  7. Huang YL, Hong HS, Wang ZW, Kuo TT: Fatal sodium valproate-induced hypersensitivity syndrome with lichenoid dermatitis and fulminant hepatitis. J Am Acad Dermatol. 2003 Aug;49(2):316-9. [12894087 ]
  8. Anderson GD, Temkin NR, Chandler WL, Winn HR: Effect of valproate on hemostatic function in patients with traumatic brain injury. Epilepsy Res. 2003 Dec;57(2-3):111-9. [15013052 ]
  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;3(6):335-42. [14597963 ]
  10. Gerstner T, Bell N, Konig S: Oral valproic acid for epilepsy--long-term experience in therapy and side effects. Expert Opin Pharmacother. 2008 Feb;9(2):285-92. doi: 10.1517/14656566.9.2.285 . [18201150 ]
  11. Russell S: Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr;19(2):206-10. [17496767 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
General function:
Involved in monooxygenase activity
Specific function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
General function:
Involved in monooxygenase activity
Specific function:
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name:
CYP3A43
Uniprot ID:
Q9HB55
Molecular weight:
57756.285
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular weight:
60845.33
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular weight:
55710.075
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
May be involved in the metabolism of various pneumotoxicants including naphthalene. Is able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but possesses no activity toward ethoxyresorufin and only trace dearylation activity toward benzyloxyresorufin. Bioactivates 3-methylindole (3MI) by dehydrogenation to the putative electrophile 3-methylene-indolenine.
Gene Name:
CYP2F1
Uniprot ID:
P24903
Molecular weight:
55500.64
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP4X1
Uniprot ID:
Q8N118
Molecular weight:
58874.62
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
General function:
Involved in monooxygenase activity
Specific function:
Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.
Gene Name:
CYP2A13
Uniprot ID:
Q16696
Molecular weight:
56687.095
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP4B1
Uniprot ID:
P13584
Molecular weight:
58990.64
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Not Available
Gene Name:
CYP4Z1
Uniprot ID:
Q86W10
Molecular weight:
59085.45
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular weight:
57882.48
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
General function:
Involved in monooxygenase activity
Specific function:
Has a potential importance for extrahepatic xenobiotic metabolism.
Gene Name:
CYP2S1
Uniprot ID:
Q96SQ9
Molecular weight:
55816.205
General function:
Involved in monooxygenase activity
Specific function:
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible for the epoxidation of endogenous cardiac arachidonic acid pools.
Gene Name:
CYP2J2
Uniprot ID:
P51589
Molecular weight:
57610.165
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2A7
Uniprot ID:
P20853
Molecular weight:
56424.735
General function:
Involved in monooxygenase activity
Specific function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular weight:
56517.005
General function:
Involved in acyl-CoA dehydrogenase activity
Specific function:
Has greatest activity toward short branched chain acyl-CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl-CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent.
Gene Name:
ACADSB
Uniprot ID:
P45954
Molecular weight:
47485.035
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP1A1
Uniprot ID:
A0N0X8
Molecular weight:
58164.8
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP2D6
Uniprot ID:
Q6NWU0
Molecular weight:
55729.9