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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:02:35 UTC
HMDB IDHMDB00355
Secondary Accession NumbersNone
Metabolite Identification
Common Name3-Hydroxymethylglutaric acid
Description3-Hydroxymethylglutaric acid is a metabolite that accumulates in the urine of patients affected by 3-Hydroxy-3-methylglutaric aciduria, a rare inborn error of metabolism (OMIM 246450 ). 3-Hydroxy-3-methylglutaric aciduria is caused by reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4), the enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. The profile of urinary organic acids is different from that of the other identified defects of leucine degradation--maple syrup urine disease (OMIM 248600 ), isovaleric acidemia (OMIM 243500 ), and methylcrotonylglycinemia (OMIM 210200 ). Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids. (PMID: 10916782 , 9658458 , 3063529 ).
Structure
Thumb
Synonyms
ValueSource
(S)-3-Hydroxy-3-methylglutaric acidChEBI
(S)-MeglutolChEBI
3-HYDROXY-3-methyl-glutarIC ACIDChEBI
beta-Hydroxy-beta-methylglutaric acidChEBI
Dicrotalic acidChEBI
MeglutolChEBI
MeglutolumChEBI
(S)-3-Hydroxy-3-methylglutarateGenerator
3-Hydroxy-3-methylpentanedioateGenerator
3-HYDROXY-3-methyl-glutarateGenerator
b-Hydroxy-b-methylglutarateGenerator
b-Hydroxy-b-methylglutaric acidGenerator
beta-Hydroxy-beta-methylglutarateGenerator
β-hydroxy-β-methylglutarateGenerator
β-hydroxy-β-methylglutaric acidGenerator
DicrotalateGenerator
3-Hydroxy-3-methylglutarateHMDB
3-Hydroxy-3-methylglutaric acidHMDB
3-HydroxymethylglutarateHMDB
3-Methyl-3-hydroxyglutarateHMDB
3-Methyl-3-hydroxyglutaric acidHMDB
CB 337HMDB
Chemical FormulaC6H10O5
Average Molecular Weight162.1406
Monoisotopic Molecular Weight162.05282343
IUPAC Name3-hydroxy-3-methylpentanedioic acid
Traditional Namemeglutol
CAS Registry Number503-49-1
SMILES
CC(O)(CC(O)=O)CC(O)=O
InChI Identifier
InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)
InChI KeyInChIKey=NPOAOTPXWNWTSH-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound 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
  • Hydroxy fatty acid
  • Methyl-branched fatty acid
  • Short-chain hydroxy acid
  • Branched fatty acid
  • Beta-hydroxy acid
  • Hydroxy acid
  • Dicarboxylic acid or derivatives
  • Tertiary alcohol
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point105 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility275.0 mg/mLALOGPS
logP-0.88ALOGPS
logP-0.75ChemAxon
logS0.23ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity34.14 m3·mol-1ChemAxon
Polarizability14.55 Å3ChemAxon
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)splash10-0002-0930000000-67cdb23f1a51498bb80dView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-05nb-2950000000-10da019551eceff729ecView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-05fr-2900000000-d5b3d7ccc3617f392a63View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-004i-9800000000-1a510972071bf02a23f7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0kdi-9300000000-6afee652d0eb18e589c3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-03di-0900000000-ae679b03ae8cdbc1cc40View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0002-9300000000-8d7565d3b9cbed5d13acView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0a4i-9000000000-d06ad8ce44567793a49dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a4i-9000000000-f3c4c2c0cb3ff49db482View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4i-9000000000-98c0337e0bebe4fefe6cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-01qa-2900000000-182405b2867309ab7df8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-03dj-5900000000-d9ffa79e6b62296f2626View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-a3631689983e6d6a3be7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-002b-2900000000-54e16eaede819dea2bdcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-9600000000-31a4e319505eebd3d1d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03xr-2900000000-405383db70ec0564b916View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-07bg-5900000000-dfc057320722ae1d926cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4m-9300000000-e5a720c14cbc5de82d4dView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Saliva
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
SalivaDetected and Quantified0.0201 +/- 0.0639 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified0.0917 +/- 0.0851 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
UrineDetected and Quantified6.788 +/- 4.222 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified27.0 (6.0-73.0) umol/mmol creatinineNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified1.4 (0.7-3.0) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified3 (0-10) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<31.61 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified2.8 (1.1 -5.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified28.1 (10.7-57.5) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified10.3 (4.3-31.4) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified9.9 (5.7-14.4) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified51.7 (13.1-101.1) umol/mmol creatinineInfant (0-1 year old)FemaleNormal details
UrineDetected and Quantified7.1 (2.2-24.5) umol/mmol creatinineAdolescent (13-18 years old)Not SpecifiedNormal details
UrineDetected and Quantified3.2(1.1-5.2) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified27.9 (6.2-49.7) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified12.098 +/- 6.49 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified10.581 +/- 10.628 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified5600.0 (200.0-11000.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency details
UrineDetected and Quantified17.227 +/- 8.202 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified31.947 +/- 39.294 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
Associated Disorders and Diseases
Disease References
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
  1. MetaGene [Link]
Associated OMIM IDs
  • 246450 (3-Hydroxy-3-methylglutaryl-CoA lyase deficiency)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB005950
KNApSAcK IDNot Available
Chemspider ID1600
KEGG Compound IDC03761
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Link3-Hydroxy-3-methylglutaric acid
NuGOwiki LinkHMDB00355
Metagene LinkHMDB00355
METLIN ID5344
PubChem Compound1662
PDB IDMAH
ChEBI ID16831
References
Synthesis ReferenceKlosterman, Harold J.; Smith, F. The isolation of b-hydroxy-b-methylglutaric acid from the seed of flax (Linum usitatissimum). Journal of the American Chemical Society (1954), 76 1229-30.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Fu Z, Runquist JA, Forouhar F, Hussain M, Hunt JF, Miziorko HM, Kim JJ: Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria. J Biol Chem. 2006 Mar 17;281(11):7526-32. Epub 2005 Dec 5. [16330550 ]
  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. [8087979 ]
  3. Mitchell GA, Jakobs C, Gibson KM, Robert MF, Burlina A, Dionisi-Vici C, Dallaire L: Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. Prenat Diagn. 1995 Aug;15(8):725-9. [7479590 ]
  4. Wysocki SJ, Wilkinson SP, Hahnel R, Wong CY, Panegyres PK: 3-Hydroxy-3-methylglutaric aciduria, combined with 3-methylglutaconic aciduria. Clin Chim Acta. 1976 Aug 2;70(3):399-406. [947633 ]
  5. Tuchman M, McCann MT, Johnson PE, Lemieux B: Screening newborns for multiple organic acidurias in dried filter paper urine samples: method development. Pediatr Res. 1991 Oct;30(4):315-21. [1956713 ]
  6. Truscott RJ, Halpern B, Wysocki SJ, Hahnel R, Wilcken B: Studies on a child suspected of having a dficiency in 3-hydroxy-3-methylglutaryl-Co A lyase. Clin Chim Acta. 1979 Jul 2;95(1):11-16. [509721 ]
  7. Koling S, Kalhoff H, Schauerte P, Lehnert W, Diekmann L: [3-hydroxy-3-methylglutaraciduria (case report of a female Turkish sisters with 3-hydroxy-3- methylglutaryl-Coenzyme A lyase deficiency]. Klin Padiatr. 2000 May-Jun;212(3):113-6. [10916782 ]
  8. Eiris J, Ribes A, Fernandez-Prieto R, Rodriguez-Garcia J, Rodriguez-Segade S, Castro-Gago M: [3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome]. Rev Neurol. 1998 Jun;26(154):911-4. [9658458 ]
  9. Gibson KM, Breuer J, Nyhan WL: 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. Eur J Pediatr. 1988 Dec;148(3):180-6. [3063529 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.
Gene Name:
HMGCL
Uniprot ID:
P35914
Molecular weight:
34359.84