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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-12-07 01:19:31 UTC
HMDB IDHMDB0000754
Secondary Accession Numbers
  • HMDB00754
Metabolite Identification
Common Name3-Hydroxyisovaleric acid
Description3-Hydroxyisovaleric acid is a normal human metabolite excreted in the urine. Elevated levels of this compound are found in several inherited disorders such as dihydrolipoamide dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase 1 deficiency, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, biotinidase deficiency, late onset multiple carboxylase deficiency, holocarboxylase synthetase deficiency, 3-methylcrotonyl-CoA carboxylase 2 deficiency, 3-methylglutaconic aciduria type I. 3-Hydroxyisovaleric acid is also elevated in smokers, in subjects undergoing long-term anticonvulsant therapy with carbamazepine and/or phenytoin. These levels are elevated due to impairment of renal reclamation of biotin. Levels may also be increased from prolonged consumption of raw egg-whites (PMID: 16895887 , 9523856 , 15447901 , 9176832 )(OMIM: 210210 , 253270 , 600529 , 253260 , 246450 , 210200 , 238331 ).
Structure
Thumb
Synonyms
ValueSource
3-Hydroxy-3-methylbutyric acidChEBI
3-Hydroxy-isovaleric acidChEBI
3-Methyl-3-hydroxybutyric acidChEBI
3-OH-Isovaleric acidChEBI
beta-Hydroxy-beta-methylbutyric acidChEBI
beta-Hydroxyisovaleric acidChEBI
HMBChEBI
HMB-D6ChEBI
3-Hydroxy-3-methylbutyrateGenerator
3-HydroxyisovalerateGenerator
3-Hydroxy-isovalerateGenerator
3-Methyl-3-hydroxybutyrateGenerator
3-OH-IsovalerateGenerator
b-Hydroxy-b-methylbutyrateGenerator
b-Hydroxy-b-methylbutyric acidGenerator
beta-Hydroxy-beta-methylbutyrateGenerator
β-hydroxy-β-methylbutyrateGenerator
β-hydroxy-β-methylbutyric acidGenerator
b-HydroxyisovalerateGenerator
b-Hydroxyisovaleric acidGenerator
beta-HydroxyisovalerateGenerator
β-hydroxyisovalerateGenerator
β-hydroxyisovaleric acidGenerator
3-Hydroxy-3-methyl-butanoateHMDB
3-Hydroxy-3-methyl-butanoic acidHMDB
3-Hydroxy-3-methyl-butyric acidHMDB
3-Hydroxy-3-methylbutanoateHMDB
3-Hydroxy-3-methylbutanoic acidHMDB
beta Hydroxy beta methylbutyrateMeSH
beta-Hydroxy beta-methylbutyrateMeSH
Chemical FormulaC5H10O3
Average Molecular Weight118.1311
Monoisotopic Molecular Weight118.062994186
IUPAC Name3-hydroxy-3-methylbutanoic acid
Traditional Name3-hydroxyisovaleric acid
CAS Registry Number625-08-1
SMILES
CC(C)(O)CC(O)=O
InChI Identifier
InChI=1S/C5H10O3/c1-5(2,8)3-4(6)7/h8H,3H2,1-2H3,(H,6,7)
InChI KeyAXFYFNCPONWUHW-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassFatty Acyls
Direct ParentHydroxy fatty acids
Alternative Parents
Substituents
  • Methyl-branched fatty acid
  • Short-chain hydroxy acid
  • Hydroxy fatty acid
  • Branched fatty acid
  • Tertiary alcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

  Health condition:

    Metabolism and nutrition disorders:

    Cancer:

Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Cell and elements:

    Cell:

Source:

  Biological:

    Animal:

Route of exposure:

  Enteral:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

    Chemical reaction:

    Biochemical process:

Role

Indirect biological role:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point65 - 67 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility384 g/LALOGPS
logP-0.12ALOGPS
logP-0.11ChemAxon
logS0.51ALOGPS
pKa (Strongest Acidic)4.55ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity28.1 m³·mol⁻¹ChemAxon
Polarizability11.75 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000t-0900000000-56f9e1ee9e19bacfc939View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000t-0900000000-56f9e1ee9e19bacfc939View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9100000000-0809a885d114ba6b21d7View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0089-6910000000-3573bf97996ef7107955View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-9300000000-e715db06e575104deccdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-9000000000-885e3d959712c9998250View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0avi-9800000000-f0296f537bd22b26f173View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ue9-5900000000-2f664d0b967c87e7358cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zn9-9500000000-233e5cd462b504c09d3cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-62361f03b7c7a0d82bc4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00xr-9400000000-13e4ec512c0fde3123abView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05tb-9200000000-96c7d7b3f54e7377a875View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0aba-9000000000-3cc71227974213e131c4View in MoNA
MSMass Spectrum (Electron Ionization)splash10-052f-9000000000-c15a37ad10e6379350aaView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue Location
  • Fibroblasts
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.0 (0.0 - 10.0) uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected but not Quantified Adult (>18 years old)Female
Normal
details
BloodDetected and Quantified<10 uMAdult (>18 years old)FemaleNormal details
BloodDetected but not Quantified Adult (>18 years old)Both
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified4.0 +/- 2.0 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified<10 uMAdult (>18 years old)FemaleNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected but not Quantified Adult (>18 years old)MaleNormal details
UrineDetected and Quantified<50 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified<50 umol/mmol creatinineChildren (1 - 13 years old)FemaleNormal details
UrineDetected and Quantified6 +/- 4 umol/mmol creatinineChildren (1 - 13 years old)Not SpecifiedNormal details
UrineDetected and Quantified12.2 (0.1-43.2) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified7.5 (5.1-23.1) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified9.0 (3.1-17.4) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified4.3-5.7 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified11.427 +/- 7.8 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified3.56 umol/mmol creatinineAdult (>18 years old)Male
Normal
    • Shaykhutdinov RA,...
details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified2.0 (0.0-4.0) umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified15.0 (5.0-26.0) umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected but not Quantified Adult (>18 years old)BothNormal details
UrineDetected and Quantified11 (6.9-25) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<68 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified4.5-6.3 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified26.9 (9.1-66.4) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified7.4 (4.1-17.2) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified6.8 (3.2-21.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified10.50 (7.02 – 14.38) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Lorena Ivona ŞTEF...
details
UrineDetected and Quantified40.486 +/- 23.766 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified8.5 +/- 3.2 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified9.5 (0.00-19.00) uMAdult (>18 years old)BothBiotinidase deficiency
    • MetaGene: Metabol...
details
BloodDetected and Quantified88.0 (10.0-166.0) uMChildren (1-13 years old)BothBiotinidase deficiency
    • MetaGene: Metabol...
details
BloodDetected and Quantified7.38 +/- 4.18 uMAdult (>18 years old)Female
Pregnancy with fetuses with trisomy 18
details
BloodDetected and Quantified5.24` 3.84 uMAdult (>18 years old)FemalePregnancy details
BloodDetected and Quantified9.2 (1.7) uMAdult (>18 years old)FemaleEarly preeclampsia details
BloodDetected and Quantified7.6 (3.1) uMAdult (>18 years old)FemalePregnancy details
BloodDetected and Quantified20 uMAdult (>18 years old)Female3-methylglutaconic aciduria type I details
BloodDetected and Quantified10.0 (10.0 - 20.0) uMAdult (>18 years old)Both
3-Methylglutaconic aciduria type I
details
BloodDetected and Quantified6.5 (3.3) uMAdult (>18 years old)FemaleLate-onset preeclampsia details
BloodDetected and Quantified4.7 (2.5) uMAdult (>18 years old)FemalePregnancy details
BloodDetected but not Quantified Adult (>18 years old)Both
Pancreatic
details
Cerebrospinal Fluid (CSF)Detected and Quantified12 uMChildren (1 - 13 years old)Not SpecifiedIsolated 3-Methylcrotonyl-CoA Carboxylase Deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified172 uMAdult (>18 years old)Female3-methylglutaconic aciduria type I details
FecesDetected but not Quantified Adult (>18 years old)BothColorectal Cancer details
UrineDetected and Quantified851 umol/mmol creatinineAdult (>18 years old)Female3-Hydroxy-3-Methylglutaryl- CoA Lyase Deficiency details
UrineDetected and Quantified1154.8 umol/mmol creatinineNewborn (0-30 days old)Male3-hydroxy-3-methylglutaric- coenzyme A lyase deficiency details
UrineDetected and Quantified2974 umol/mmol creatinineChildren (1 - 13 years old)Not SpecifiedIsolated 3-Methylcrotonyl-CoA Carboxylase Deficiency details
UrineDetected and Quantified1900 +/- 500 umol/mmol creatinineAdult (>18 years old)Both3-Methylcrotonyl-CoA Carboxylase Deficiency details
UrineDetected and Quantified210-230 umol/mmol creatinineChildren (1 - 13 years old)FemaleLeigh's syndrome details
UrineDetected and Quantified275.0 (50.0-500.0) umol/mmol creatinineChildren (1-13 years old)BothBiotinidase deficiency
    • MetaGene: Metabol...
details
UrineDetected and Quantified12.757 +/- 10.313 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected but not Quantified Adult (>18 years old)BothAutosomal dominant polycystic kidney disease (ADPKD) details
UrineDetected and Quantified6.0 +/- 2.0 umol/mmol creatinineAdult (>18 years old)BothLung cancer details
UrineDetected and Quantified10.78 (4.94 – 21.07) umol/mmol creatinineAdult (>18 years old)BothType 1 diabetes Mellitus
    • Lorena Ivona ŞTEF...
details
UrineDetected and Quantified247.428 +/- 452.008 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified119.783 +/- 114.263 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected and Quantified23.0 (0.0-46.0) umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
    • MetaGene: Metabol...
details
UrineDetected and Quantified2030.0 (60.0-4000.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
    • MetaGene: Metabol...
details
Associated Disorders and Diseases
Disease References
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  1. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
3-Methylglutaconic aciduria type I
  1. Engelke UF, Kremer B, Kluijtmans LA, van der Graaf M, Morava E, Loupatty FJ, Wanders RJ, Moskau D, Loss S, van den Bergh E, Wevers RA: NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed. 2006 Apr;19(2):271-8. [PubMed:16541463 ]
Biotinidase deficiency
  1. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Lung Cancer
  1. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2009 Jan;37(Database issue):D603-10. doi: 10.1093/nar/gkn810. Epub 2008 Oct 25. [PubMed:18953024 ]
Associated OMIM IDs
  • 250950 (3-Methylglutaconic aciduria type I)
  • 211980 (Lung Cancer)
  • 246450 (3-Hydroxy-3-methylglutaryl-CoA lyase deficiency)
  • 253260 (Biotinidase deficiency)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022225
KNApSAcK IDNot Available
Chemspider ID62571
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID5722
PubChem Compound69362
PDB IDNot Available
ChEBI ID37084
References
Synthesis ReferenceRudney, Harry. Biosynthesis of b-hydroxy-b-methylglutaric acid. Journal of Biological Chemistry (1957), 227 363-77.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Boulat O, Gradwohl M, Matos V, Guignard JP, Bachmann C: Organic acids in the second morning urine in a healthy Swiss paediatric population. Clin Chem Lab Med. 2003 Dec;41(12):1642-58. [PubMed:14708889 ]
  2. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. [PubMed:8087979 ]
  3. Mock DM, Stadler DD: Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. J Am Coll Nutr. 1997 Jun;16(3):252-7. [PubMed:9176832 ]
  4. Baykal T, Gokcay GH, Ince Z, Dantas MF, Fowler B, Baumgartner MR, Demir F, Can G, Demirkol M: Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome. J Inherit Metab Dis. 2005;28(2):229-33. [PubMed:15877210 ]
  5. Amberg A, Rosner E, Dekant W: Biotransformation and kinetics of excretion of tert-amyl-methyl ether in humans and rats after inhalation exposure. Toxicol Sci. 2000 Jun;55(2):274-83. [PubMed:10828258 ]
  6. Schurmann M, Engelbrecht V, Lohmeier K, Lenard HG, Wendel U, Gartner J: Cerebral metabolic changes in biotinidase deficiency. J Inherit Metab Dis. 1997 Nov;20(6):755-60. [PubMed:9427142 ]
  7. Sealey WM, Teague AM, Stratton SL, Mock DM: Smoking accelerates biotin catabolism in women. Am J Clin Nutr. 2004 Oct;80(4):932-5. [PubMed:15447901 ]
  8. Jakobs C, Sweetman L, Nyhan WL, Packman S: Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism. J Inherit Metab Dis. 1984;7(1):15-20. [PubMed:6429435 ]
  9. Santer R, Muhle H, Suormala T, Baumgartner ER, Duran M, Yang X, Aoki Y, Suzuki Y, Stephani U: Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. Mol Genet Metab. 2003 Jul;79(3):160-6. [PubMed:12855220 ]
  10. Rodriguez JM, Ruiz-Sala P, Ugarte M, Penalva MA: Fungal metabolic model for 3-methylcrotonyl-CoA carboxylase deficiency. J Biol Chem. 2004 Feb 6;279(6):4578-87. Epub 2003 Nov 11. [PubMed:14612443 ]
  11. Stratton SL, Bogusiewicz A, Mock MM, Mock NI, Wells AM, Mock DM: Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans. Am J Clin Nutr. 2006 Aug;84(2):384-8. [PubMed:16895887 ]
  12. Mock DM, Mock NI, Nelson RP, Lombard KA: Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr. 1998 Mar;26(3):245-50. [PubMed:9523856 ]

Enzymes

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
Reactions
3-Hydroxyisovaleric acid → 6-[(1-carboxy-2-methylpropan-2-yl)oxy]-3,4,5-trihydroxyoxane-2-carboxylic aciddetails
3-Hydroxyisovaleric acid → 3,4,5-trihydroxy-6-[(3-hydroxy-3-methylbutanoyl)oxy]oxane-2-carboxylic aciddetails