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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:30 UTC
HMDB IDHMDB00901
Secondary Accession NumbersNone
Metabolite Identification
Common NameValproic acid glucuronide
DescriptionValproic acid glucuronide is the glucuronidation product of valproic acid. Valproic acid, or 2-Propylpentanoic acid, is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder, but also used to treat migraine headaches and schizophrenia. 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. Glucuronidation is a vital phase 2 metabolic (conjugative) process by which a wide range of drugs and other xenobiotics may be rendered water-soluble, detoxified and excreted. Acyl (ester) glucuronides (AGs) of carboxylic acids are potentially reactive metabolites. In particular, AGs are important phase 2 metabolites for a wide range of carboxylic acid-containing drugs. (PMID: 18201150 , 17496767 , 17496206 ).
Structure
Thumb
Synonyms
ValueSource
1-(2-PropylpentanoateHMDB
1-(2-Propylpentanoate) beta-D-glucopyranuronateHMDB
1-(2-Propylpentanoate) beta-D-glucopyranuronic acidHMDB
1-(2-Propylpentanoate) beta-delta-glucopyranuronateHMDB
1-(2-Propylpentanoate) beta-delta-glucopyranuronic acidHMDB
1-(2-Propylpentanoic acidHMDB
1-O-Valproyl-b-D-glucopyranuronic acidHMDB
1-O-Valproyl-beta-delta-glucopyranuronic acidHMDB
3,4,5-Trihydroxy-6-(2-propyl-pentanoyloxy)-tetrahydro-pyran-2-carboxylateHMDB
3,4,5-Trihydroxy-6-(2-propyl-pentanoyloxy)-tetrahydro-pyran-2-carboxylic acidHMDB
Dipropylacetate glucuronideHMDB
MyproateHMDB
Myproic acidHMDB
ValproateHMDB
Valproate glucuronideHMDB
Valproic acidHMDB
VPA-gHMDB
VPAGHMDB
Chemical FormulaC14H24O8
Average Molecular Weight320.3356
Monoisotopic Molecular Weight320.147117744
IUPAC Name(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(2-propylpentanoyl)oxy]oxane-2-carboxylic acid
Traditional Name(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[(2-propylpentanoyl)oxy]oxane-2-carboxylic acid
CAS Registry Number60113-83-9
SMILES
CCCC(CCC)C(=O)O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C(O)=O
InChI Identifier
InChI=1S/C14H24O8/c1-3-5-7(6-4-2)13(20)22-14-10(17)8(15)9(16)11(21-14)12(18)19/h7-11,14-17H,3-6H2,1-2H3,(H,18,19)/t8-,9-,10+,11-,14-/m0/s1
InChI KeyInChIKey=XXKSYIHWRBBHIC-JVWRJRKNSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as o-glucuronides. These are glucuronides in which the aglycone is linked to the carbohydrate unit through an O-glycosidic bond.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassSugar acids and derivatives
Direct ParentO-glucuronides
Alternative Parents
Substituents
  • O-glucuronide
  • 1-o-glucuronide
  • Pyran carboxylic acid
  • Pyran carboxylic acid or derivatives
  • Fatty acid ester
  • Beta-hydroxy acid
  • Fatty acyl
  • Pyran
  • Oxane
  • Monosaccharide
  • Hydroxy acid
  • Dicarboxylic acid or derivatives
  • Secondary alcohol
  • Polyol
  • Carboxylic acid ester
  • 1,2-diol
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Carbonyl group
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug metabolite
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
  • Waste products
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP0.85Extrapolated
Predicted Properties
PropertyValueSource
Water Solubility22.2 mg/mLALOGPS
logP0.2ALOGPS
logP0.85ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)3.41ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area133.52 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity72.55 m3·mol-1ChemAxon
Polarizability32.52 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Brain
  • Kidney
  • Liver
  • Pancreas
  • Placenta
  • Platelet
Pathways
NameSMPDB LinkKEGG Link
Valproic Acid Metabolism PathwaySMP00635Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00512
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022308
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDBeta-D-Glucuronides
BiGG IDNot Available
Wikipedia LinkValproic acid
NuGOwiki LinkHMDB00901
Metagene LinkHMDB00901
METLIN ID2991
PubChem Compound53477719
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceYamamura, Naotoshi; Muramatsu, Shigeki; Suzuki, Kanae; Uchiyama, Minoru; Nakajima, Eiichi. High-yield, enzymic synthesis of 14C- or 3H-labeled 1-O-valproyl-b-D-glucopyranuronic acid, the main metabolite of valproic acid in human. Radioisotopes (1999), 48(
Material Safety Data Sheet (MSDS)Not Available
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. Yoshida H, Hirozane K, Kimoto H, Hayashi T, Akiyama T, Katayama H, Watanabe M, Yoshitomi H, Kamiya A: Valproic acid elimination rate and urinary excretion of its glucuronide conjugate in patients with epilepsy. Biol Pharm Bull. 1999 Jul;22(7):716-20. [10443469 ]
  5. 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 ]
  6. 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 ]
  7. Bailey DN, Briggs JR: Valproic acid binding to human serum and human placenta in vitro. Ther Drug Monit. 2005 Jun;27(3):375-7. [15905810 ]
  8. Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM, Rice HE: Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun. 2002 Jun 7;294(2):371-9. [12051722 ]
  9. Queizan A, Hernandez F, Rivas S: Pancreatic pseudocyst caused by valproic acid: case report and review of the literature. Eur J Pediatr Surg. 2003 Feb;13(1):60-2. [12664419 ]
  10. 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 ]
  11. Fowler DW, Eadie MJ, Dickinson RG: Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta. J Pharmacol Exp Ther. 1989 Apr;249(1):318-23. [2496226 ]
  12. Serdaroglu G, Erhan E, Tekgul H, Oksel F, Erermis S, Uyar M, Tutuncuoglu S: Sodium valproate prophylaxis in childhood migraine. Headache. 2002 Sep;42(8):819-22. [12390647 ]
  13. Kim JM, Jung KY, Choi CM: Changes in brain complexity during valproate treatment in patients with partial epilepsy. Neuropsychobiology. 2002;45(2):106-12. [11893868 ]
  14. 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 ]
  15. Dickinson RG, Kluck RM, Hooper WD, Patterson M, Chalk JB, Eadie MJ: Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction. Epilepsia. 1985 Nov-Dec;26(6):589-93. [3935422 ]
  16. Williams AM, Worrall S, de Jersey J, Dickinson RG: Studies on the reactivity of acyl glucuronides--III. Glucuronide-derived adducts of valproic acid and plasma protein and anti-adduct antibodies in humans. Biochem Pharmacol. 1992 Feb 18;43(4):745-55. [1540228 ]
  17. Nakamura H, Ushigome F, Koyabu N, Satoh S, Tsukimori K, Nakano H, Ohtani H, Sawada Y: Proton gradient-dependent transport of valproic acid in human placental brush-border membrane vesicles. Pharm Res. 2002 Feb;19(2):154-61. [11883642 ]
  18. De Berardis D, Campanella D, Matera V, Gambi F, La Rovere R, Sepede G, Grimaldi MR, Pacilli AM, Salerno RM, Ferro FM: Thrombocytopenia during valproic acid treatment in young patients with new-onset bipolar disorder. J Clin Psychopharmacol. 2003 Oct;23(5):451-8. [14520121 ]
  19. 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 ]
  20. Mallet L, Babin S, Morais JA: Valproic acid-induced hyperammonemia and thrombocytopenia in an elderly woman. Ann Pharmacother. 2004 Oct;38(10):1643-7. Epub 2004 Aug 17. [15316109 ]
  21. Wong H, Tong V, Riggs KW, Rurak DW, Abbott FS, Kumar S: Kinetics of valproic acid glucuronidation: evidence for in vivo autoactivation. Drug Metab Dispos. 2007 Aug;35(8):1380-6. Epub 2007 May 11. [17496206 ]
  22. 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 ]
  23. 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 transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme has glucuronidating capacity with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems to be active.
Gene Name:
UGT2B28
Uniprot ID:
Q9BY64
Molecular weight:
38742.9
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
Gene Name:
UGT2B4
Uniprot ID:
P06133
Molecular weight:
60512.035
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
References
  1. Ethell BT, Anderson GD, Burchell B: The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochem Pharmacol. 2003 May 1;65(9):1441-9. [12732356 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. It also catalyzes the glucuronidation of endogenous estrogens and androgens.
Gene Name:
UGT2B15
Uniprot ID:
P54855
Molecular weight:
61035.815
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Active on odorants and seems to be involved in olfaction; it could help clear lipophilic odorant molecules from the sensory epithelium.
Gene Name:
UGT2A1
Uniprot ID:
Q9Y4X1
Molecular weight:
60771.605
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
References
  1. Ethell BT, Anderson GD, Burchell B: The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochem Pharmacol. 2003 May 1;65(9):1441-9. [12732356 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A3
Uniprot ID:
P35503
Molecular weight:
60337.835
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The major substrates of this isozyme are eugenol > 4-methylumbelliferone > dihydrotestosterone (DHT) > androstane-3-alpha,17-beta-diol (3-alpha-diol) > testosterone > androsterone (ADT).
Gene Name:
UGT2B17
Uniprot ID:
O75795
Molecular weight:
61094.915
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A6
Uniprot ID:
P19224
Molecular weight:
60750.215
References
  1. Ethell BT, Anderson GD, Burchell B: The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochem Pharmacol. 2003 May 1;65(9):1441-9. [12732356 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A5
Uniprot ID:
P35504
Molecular weight:
60070.565
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT2B11
Uniprot ID:
O75310
Molecular weight:
61037.8
General function:
Involved in hydrolase activity, hydrolyzing O-glycosyl compounds
Specific function:
Plays an important role in the degradation of dermatan and keratan sulfates.
Gene Name:
GUSB
Uniprot ID:
P08236
Molecular weight:
74731.46
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).
Gene Name:
UGT2A3
Uniprot ID:
Q6UWM9
Molecular weight:
60253.94
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A10
Uniprot ID:
Q5DT02
Molecular weight:
59809.1
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A8
Uniprot ID:
Q5DSZ6
Molecular weight:
59741.0
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A7
Uniprot ID:
Q5DSZ7
Molecular weight:
59818.3