Hmdb loader
Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2023-05-30 20:56:02 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. It is a byproduct of the leucine degradation pathway. Production of 3-hydroxyisovaleric acid begins with the conversion of 3-methylcrotonyl-CoA into 3-methylglutaconyl-CoA in the mitochondria by the biotin-dependent enzyme methylcrotonyl-CoA carboxylase. Biotin deficiencies, certain lifestyle habits (smoking), or specific genetic conditions can reduce methylcrotonyl-CoA carboxylase activity. This reduction can lead to a buildup of 3-methylcrotonyl-CoA, which is converted into 3-hydroxyisovaleryl-CoA by the enzyme enoyl-CoA hydratase. Increased concentrations of 3-methylcrotonyl-CoA and 3-hydroxyisovaleryl-CoA can lead to a disruption of the esterified CoA:free CoA ratio, and ultimately to mitochondrial toxicity. Detoxification of these metabolic end products occur via the transfer of the 3-hydroxyisovaleryl moiety to carnitine forming 3-hydroxyisovaleric acid-carnitine or 3HIA-carnitine, which is then transferred across the inner mitochondrial membrane where 3-hydroxyisovaleric acid is released as the free acid (PMID: 21918059 ). 3-Hydroxyisovaleric acid has been found to be elevated in smokers and 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 ). When present in sufficiently high levels, 3-hydroxyisovaleric acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of 3-hydroxyisovaleric acid are associated with at least a dozen inborn errors of metabolism, including 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methylglutaconic aciduria type I, biotinidase deficiency and isovaleric aciduria, dihydrolipoamide dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase 1 deficiency, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, late-onset multiple carboxylase deficiency, holocarboxylase synthetase deficiency, and 3-methylcrotonyl-CoA carboxylase 2 deficiency. 3-Hydroxyisovaleric acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Structure
Data?1676999708
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-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-HydroxyisovalerateGenerator
beta Hydroxy beta methylbutyrateHMDB
beta-Hydroxy beta-methylbutyrateHMDB
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
3-Hydroxyisovaleric acidMeSH
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
Description Belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
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
Disposition
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point65 - 67 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP6.300The Good Scents Company Information System
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+124.8331661259
DarkChem[M-H]-118.43831661259
AllCCS[M+H]+127.48832859911
AllCCS[M-H]-125.81432859911
DeepCCS[M+H]+128.27330932474
DeepCCS[M-H]-125.41630932474
DeepCCS[M-2H]-161.78930932474
DeepCCS[M+Na]+136.72830932474
AllCCS[M+H]+127.532859911
AllCCS[M+H-H2O]+123.332859911
AllCCS[M+NH4]+131.432859911
AllCCS[M+Na]+132.532859911
AllCCS[M-H]-125.832859911
AllCCS[M+Na-2H]-129.232859911
AllCCS[M+HCOO]-132.932859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
3-Hydroxyisovaleric acidCC(C)(O)CC(O)=O2194.1Standard polar33892256
3-Hydroxyisovaleric acidCC(C)(O)CC(O)=O956.3Standard non polar33892256
3-Hydroxyisovaleric acidCC(C)(O)CC(O)=O992.0Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
3-Hydroxyisovaleric acid,1TMS,isomer #1CC(C)(CC(=O)O)O[Si](C)(C)C1144.9Semi standard non polar33892256
3-Hydroxyisovaleric acid,1TMS,isomer #2CC(C)(O)CC(=O)O[Si](C)(C)C1046.0Semi standard non polar33892256
3-Hydroxyisovaleric acid,2TMS,isomer #1CC(C)(CC(=O)O[Si](C)(C)C)O[Si](C)(C)C1216.4Semi standard non polar33892256
3-Hydroxyisovaleric acid,1TBDMS,isomer #1CC(C)(CC(=O)O)O[Si](C)(C)C(C)(C)C1403.1Semi standard non polar33892256
3-Hydroxyisovaleric acid,1TBDMS,isomer #2CC(C)(O)CC(=O)O[Si](C)(C)C(C)(C)C1268.8Semi standard non polar33892256
3-Hydroxyisovaleric acid,2TBDMS,isomer #1CC(C)(CC(=O)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C1657.2Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental GC-MSGC-MS Spectrum - 3-Hydroxyisovaleric acid GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-000t-0900000000-56f9e1ee9e19bacfc9392014-06-16HMDB team, MONA, MassBankView Spectrum
Experimental GC-MSGC-MS Spectrum - 3-Hydroxyisovaleric acid GC-EI-TOF (Non-derivatized)splash10-000t-0900000000-56f9e1ee9e19bacfc9392017-09-12HMDB team, MONA, MassBankView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9100000000-0809a885d114ba6b21d72017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (2 TMS) - 70eV, Positivesplash10-0089-6910000000-3573bf97996ef71079552017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - 3-Hydroxyisovaleric acid GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-11-05Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-052f-9000000000-c15a37ad10e6379350aa2014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 35V, Negative-QTOFsplash10-0006-9000000000-1381eacc487b12932a432021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 20V, Negative-QTOFsplash10-00dj-9000000000-f10c5afd9954f294ea912021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 10V, Negative-QTOFsplash10-00xr-9600000000-3b24b27c64b89a6a5b252021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid Quattro_QQQ 10V, Positive-QTOF (Annotated)splash10-0a4i-9300000000-e715db06e575104deccd2012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid Quattro_QQQ 25V, Positive-QTOF (Annotated)splash10-0a4i-9000000000-885e3d959712c99982502012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid Quattro_QQQ 40V, Positive-QTOF (Annotated)splash10-0avi-9800000000-f0296f537bd22b26f1732012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 35V, Positive-QTOFsplash10-014i-1900000000-b947237de42eec92a67e2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 10V, Negative-QTOFsplash10-00xr-9400000000-13e4ec512c0fde3123ab2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 20V, Negative-QTOFsplash10-05tb-9200000000-96c7d7b3f54e7377a8752017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 40V, Negative-QTOFsplash10-0aba-9000000000-3cc71227974213e131c42017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 10V, Negative-QTOFsplash10-00kb-9400000000-9721ad435e43092a072d2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 20V, Negative-QTOFsplash10-0a4i-9000000000-13f5bd4a628f51aec8102021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 40V, Negative-QTOFsplash10-052f-9000000000-0eeab2c474971ae60e7b2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 10V, Positive-QTOFsplash10-0ue9-5900000000-2f664d0b967c87e7358c2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 20V, Positive-QTOFsplash10-0zn9-9500000000-233e5cd462b504c09d3c2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 40V, Positive-QTOFsplash10-0a4i-9000000000-62361f03b7c7a0d82bc42017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 10V, Positive-QTOFsplash10-0udi-8900000000-a25104a0136877edd57e2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 20V, Positive-QTOFsplash10-052f-9000000000-d2d6bcff64e0a706fc952021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 3-Hydroxyisovaleric acid 40V, Positive-QTOFsplash10-0006-9000000000-65f5183bc669daba34f42021-09-22Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-24Wishart LabView Spectrum
Experimental 1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)2021-10-10Wishart LabView Spectrum
Experimental 1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)2021-10-10Wishart LabView Spectrum
Experimental 2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)2012-12-05Wishart LabView Spectrum

IR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-)2023-02-03FELIX labView Spectrum
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+)2023-02-03FELIX labView Spectrum
Predicted IR SpectrumIR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+)2023-02-03FELIX labView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Locations
  • Fibroblasts
  • Placenta
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.0 (0.0 - 10.0) uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Female
Normal
details
BloodDetected and Quantified<10 uMAdult (>18 years old)FemaleNormal details
BloodDetected but not QuantifiedNot QuantifiedAdult (>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 QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>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
    • Analysis of 30 no...
details
UrineDetected and Quantified3.56 umol/mmol creatinineAdult (>18 years old)Male
Normal
    • Shaykhutdinov RA,...
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>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 QuantifiedNot QuantifiedAdult (>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 Quantified<46 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified0-1.3 umol/mmol creatinineInfant (0-1 year old)Male
Normal
details
UrineDetected and Quantified0-1.3 umol/mmol creatinineInfant (0-1 year old)Female
Normal
details
UrineDetected and Quantified4.5-6.3 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.0-3.2 umol/mmol creatinineInfant (0-1 year old)Female
Normal
details
UrineDetected and Quantified26.9 (9.1-66.4) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified<50 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal 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 Quantified<0.0420 umol/mmol creatinineNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified40.486 +/- 23.766 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Analysis of 30 no...
details
UrineDetected and Quantified8.5 +/- 3.2 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified7.21 (4.65-11.74) umol/mmol creatinineNewborn (0-30 days old)Both
Normal
    • Analysis of 40 NI...
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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 QuantifiedNot QuantifiedAdult (>18 years old)Both
Pancreatic cancer
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 QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothColorectal Cancer details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MaleAttachment loss  details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MalePeriodontal Probing Depth 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
    • Analysis of 30 no...
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothAutosomal dominant polycystic kidney disease (ADPKD) details
UrineDetected and Quantified1154.8 umol/mmol creatinineNewborn (0-30 days old)Male3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected and Quantified6.0 +/- 2.0 umol/mmol creatinineAdult (>18 years old)BothLung cancer details
UrineDetected and Quantified851 umol/mmol creatinineAdult (>18 years old)Female3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothBladder 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 Quantified0.0100-0.0460 umol/mmol creatinineChildren (1-13 years old)Female3-Methylglutaconic Aciduria (Type VI) details
UrineDetected and Quantified247.428 +/- 452.008 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Analysis of 30 no...
details
UrineDetected and Quantified119.783 +/- 114.263 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Analysis of 30 no...
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-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.
Pancreatic cancer
  1. OuYang D, Xu J, Huang H, Chen Z: Metabolomic profiling of serum from human pancreatic cancer patients using 1H NMR spectroscopy and principal component analysis. Appl Biochem Biotechnol. 2011 Sep;165(1):148-54. doi: 10.1007/s12010-011-9240-0. Epub 2011 Apr 20. [PubMed:21505807 ]
Early preeclampsia
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: Metabolomics and first-trimester prediction of early-onset preeclampsia. J Matern Fetal Neonatal Med. 2012 Oct;25(10):1840-7. doi: 10.3109/14767058.2012.680254. Epub 2012 Apr 28. [PubMed:22494326 ]
Pregnancy
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: Metabolomics and first-trimester prediction of early-onset preeclampsia. J Matern Fetal Neonatal Med. 2012 Oct;25(10):1840-7. doi: 10.3109/14767058.2012.680254. Epub 2012 Apr 28. [PubMed:22494326 ]
  2. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: First-trimester metabolomic detection of late-onset preeclampsia. Am J Obstet Gynecol. 2013 Jan;208(1):58.e1-7. doi: 10.1016/j.ajog.2012.11.003. Epub 2012 Nov 13. [PubMed:23159745 ]
  3. Bahado-Singh RO, Akolekar R, Chelliah A, Mandal R, Dong E, Kruger M, Wishart DS, Nicolaides K: Metabolomic analysis for first-trimester trisomy 18 detection. Am J Obstet Gynecol. 2013 Jul;209(1):65.e1-9. doi: 10.1016/j.ajog.2013.03.028. Epub 2013 Mar 25. [PubMed:23535240 ]
Late-onset preeclampsia
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: First-trimester metabolomic detection of late-onset preeclampsia. Am J Obstet Gynecol. 2013 Jan;208(1):58.e1-7. doi: 10.1016/j.ajog.2012.11.003. Epub 2012 Nov 13. [PubMed:23159745 ]
3-Methyl-crotonyl-glycinuria
  1. de Kremer RD, Latini A, Suormala T, Baumgartner ER, Larovere L, Civallero G, Guelbert N, Paschini-Capra A, Depetris-Boldini C, Mayor CQ: Leukodystrophy and CSF purine abnormalities associated with isolated 3-methylcrotonyl-CoA carboxylase deficiency. Metab Brain Dis. 2002 Mar;17(1):13-8. [PubMed:11893004 ]
  2. Thomsen JA, Lund AM, Olesen JH, Mohr M, Rasmussen J: Is L-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency? JIMD Rep. 2015;21:79-88. doi: 10.1007/8904_2014_393. Epub 2015 Mar 3. [PubMed:25732994 ]
Colorectal cancer
  1. Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
  2. Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. [PubMed:27015276 ]
  3. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Attachment loss
  1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
Periodontal Probing Depth
  1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmuller G, Artati A, Suhre K, Adamski J, Nauck M, Volzke H, Friedrich N, Kocher T, Holtfreter B, Pietzner M: The Saliva Metabolome in Association to Oral Health Status. J Dent Res. 2019 Jun;98(6):642-651. doi: 10.1177/0022034519842853. Epub 2019 Apr 26. [PubMed:31026179 ]
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 ]
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  1. Bischof F, Nagele T, Wanders RJ, Trefz FK, Melms A: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy. Ann Neurol. 2004 Nov;56(5):727-30. [PubMed:15505778 ]
  2. Santarelli F, Cassanello M, Enea A, Poma F, D'Onofrio V, Guala G, Garrone G, Puccinelli P, Caruso U, Porta F, Spada M: A neonatal case of 3-hydroxy-3-methylglutaric-coenzyme A lyase deficiency. Ital J Pediatr. 2013 May 24;39:33. doi: 10.1186/1824-7288-39-33. [PubMed:23705938 ]
  3. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Diabetes mellitus type 1
  1. (). Lorena Ivona ŞTEFAN, Alina NICOLESCU, Simona POPA, Maria MOŢA, Eugenia KOVACS and Calin DELEANU. 1H-NMR URINE METABOLIC PROFILING IN TYPE 1 DIABETES MELLITUS. Rev. Roum. Chim., 2010, 55(11-12), 1033-1037 . .
Autosomal dominant polycystic kidney disease
  1. Gronwald W, Klein MS, Zeltner R, Schulze BD, Reinhold SW, Deutschmann M, Immervoll AK, Boger CA, Banas B, Eckardt KU, Oefner PJ: Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine. Kidney Int. 2011 Jun;79(11):1244-53. doi: 10.1038/ki.2011.30. Epub 2011 Mar 9. [PubMed:21389975 ]
Eosinophilic esophagitis
  1. Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work). NA.
3-Methylglutaconic Aciduria type VI
  1. Wortmann S, Rodenburg RJ, Huizing M, Loupatty FJ, de Koning T, Kluijtmans LA, Engelke U, Wevers R, Smeitink JA, Morava E: Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. Mol Genet Metab. 2006 May;88(1):47-52. doi: 10.1016/j.ymgme.2006.01.013. Epub 2006 Mar 9. [PubMed:16527507 ]
Associated OMIM IDs
  • 250950 (3-Methylglutaconic aciduria type I)
  • 253260 (Biotinidase deficiency)
  • 260350 (Pancreatic cancer)
  • 210200 (3-Methyl-crotonyl-glycinuria)
  • 114500 (Colorectal cancer)
  • 211980 (Lung Cancer)
  • 246450 (3-Hydroxy-3-methylglutaryl-CoA lyase deficiency)
  • 222100 (Diabetes mellitus type 1)
  • 601313 (Autosomal dominant polycystic kidney disease)
  • 610247 (Eosinophilic esophagitis)
  • 614739 (3-Methylglutaconic Aciduria type VI)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022225
KNApSAcK IDNot Available
Chemspider ID62571
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBeta-Hydroxy_beta-methylbutyric_acid
METLIN ID5722
PubChem Compound69362
PDB IDNot Available
ChEBI ID37084
Food Biomarker OntologyNot Available
VMH ID3HIVAC
MarkerDB IDMDB00013435
Good Scents IDrw1687381
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 ]
  13. Mock DM, Stratton SL, Horvath TD, Bogusiewicz A, Matthews NI, Henrich CL, Dawson AM, Spencer HJ, Owen SN, Boysen G, Moran JH: Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. J Nutr. 2011 Nov;141(11):1925-30. doi: 10.3945/jn.111.146126. Epub 2011 Sep 14. [PubMed:21918059 ]
  14. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

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