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Record Information
Version4.0
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-10-23 18:14:06 UTC
HMDB IDHMDB0000694
Secondary Accession Numbers
  • HMDB00694
Metabolite Identification
Common NameL-2-Hydroxyglutaric acid
DescriptionL-2-Hydroxyglutaric acid is a metabolite that accumulates in L-2-hydroxyglutaric aciduria (a neurometabolic disorder, OMIM 236792 ), and has been reported in multiple patients who have a clinical phenotype of progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and spongiform changes in the white matter (OMIM 600721 ). L-2-hydroxyglutarate can be converted to α-ketoglutaric acid through the action of L-2-hydroxyglutarate dehydrogenase (L2HGDH). L-2-Hydroxyglutaric acid is also considered to be an oncometabolite (or cancer-causing metabolite). It can be produced via gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of TCA cycle and this compound is generated in high abundance when IDH is mutated. L-2-hydroxyglutarate is sufficiently similar in structure to 2-oxogluratate (2OG) that it is able to inhibit a range of 2OG-dependent dioxygenases, including histone lysine demethylases (KDMs) and members of the ten-eleven translocation (TET) family of 5-methylcytosine (5mC) hydroxylases. This inhibitory effect leads to alterations in the hypoxia induced factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that L-2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation.
Structure
Thumb
Synonyms
ValueSource
(R)-2-HydroxyglutarateChEBI
(R)-HydroxyglutarateChEBI
(R)-2-Hydroxyglutaric acidGenerator
D-2-HydroxyglutarateGenerator
(R)-Hydroxyglutaric acidGenerator
(R)-2-Hydroxy-pentanedioateHMDB
(R)-2-Hydroxy-pentanedioic acidHMDB
(R)-a-HydroxyglutarateHMDB
(R)-a-Hydroxyglutaric acidHMDB
(R)-alpha-HydroxyglutarateHMDB
(R)-alpha-Hydroxyglutaric acidHMDB
2-Hydroxy-D-glutarateHMDB
2-Hydroxy-D-glutaric acidHMDB
2-Hydroxy-delta-glutarateHMDB
2-Hydroxy-delta-glutaric acidHMDB
D-a-HydroxyglutarateHMDB
D-a-Hydroxyglutaric acidHMDB
delta-2-HydroxyglutarateHMDB
delta-2-Hydroxyglutaric acidHMDB
delta-alpha-HydroxyglutarateHMDB
delta-alpha-Hydroxyglutaric acidHMDB
Chemical FormulaC5H8O5
Average Molecular Weight148.114
Monoisotopic Molecular Weight148.037173366
IUPAC Name(2R)-2-hydroxypentanedioic acid
Traditional NameD-2-hydroxyglutaric acid
CAS Registry Number13095-48-2
SMILES
O[C@H](CCC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m1/s1
InChI KeyHWXBTNAVRSUOJR-GSVOUGTGSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as short-chain hydroxy acids and derivatives. These are hydroxy acids with an alkyl chain the contains less than 6 carbon atoms.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassHydroxy acids and derivatives
Direct ParentShort-chain hydroxy acids and derivatives
Alternative Parents
Substituents
  • Short-chain hydroxy acid
  • Fatty acid
  • Monosaccharide
  • Dicarboxylic acid or derivatives
  • Alpha-hydroxy acid
  • Secondary alcohol
  • 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:

    Cancer:

    Metabolism and nutrition disorders:

    Cardiac disorders:

Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Source:

Route of exposure:

  Enteral:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility157 g/LALOGPS
logP-1ALOGPS
logP-0.82ChemAxon
logS0.03ALOGPS
pKa (Strongest Acidic)3.28ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity29.63 m³·mol⁻¹ChemAxon
Polarizability12.97 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0zgl-9300000000-805667744aba36281cecView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-00gv-8191000000-f6fdffd87ffe1acf65b4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001j-1900000000-dbf80fc2b86ec60d623eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0m5r-9600000000-d1bc7ce2206164b5bc2cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-df3e77cb42d6f7647a64View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1900000000-095c1140772d4cdd149bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0zfr-7900000000-ce158ac5b56eff867735View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-e30760384709aa978986View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria Pw002452Pw002452 greyscalePw002452 simpleNot Available
Displaying 1 entry
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.5 (0.0-1.5) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1 uMChildren (1-13 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.0 +/- 1.0 uMAdult (>18 years old)Not SpecifiedNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
FecesDetected but not Quantified Not SpecifiedNot Specified
Normal
details
SalivaDetected but not Quantified Adult (>18 years old)Both
Normal
    • Zerihun T. Dame, ...
details
UrineDetected and Quantified24.379 +/- 9.126 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified51.9 (13.7-97.3) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified41.5 (14.6-150.3) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified12.4 (5.1-24.9) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified11.2 (4.6-33.6) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified2.2 (0.8-52) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<26.15 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified33.0 (13.3-77.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified33.0 (20.0-46.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified47.0 +/- 13.0 uMAdult (>18 years old)BothL-2-hydroxyglutaric aciduria details
BloodDetected and Quantified0.75 (0.0-1.5) uMAdult (>18 years old)Both2-hydroxyglutaric aciduria details
BloodDetected and Quantified33.3 (7.0-61.0) uMChildren (1-13 years old)BothL-2-hydroxyglutaric aciduria details
UrineDetected and Quantified61.074 +/- 36.982 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified50.00-4300.00 umol/mmol creatinineChildren (1-13 years old)BothD, L-2-hydroxyglutaric aciduria details
Associated Disorders and Diseases
Disease References
2-hydroxyglutaric aciduria
    MetaGene
L-2-hydroxyglutaric aciduria
  1. Gibson KM, ten Brink HJ, Schor DS, Kok RM, Bootsma AH, Hoffmann GF, Jakobs C: Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias. Pediatr Res. 1993 Sep;34(3):277-80. [PubMed:8134166 ]
D, L-2-hydroxygluraric aciduria
    MetaGene
Associated OMIM IDs
  • 236792 (L-2-hydroxyglutaric aciduria)
  • 236792 (2-hydroxyglutaric aciduria)
  • 615182 (D, L-2-hydroxygluraric aciduria)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022185
KNApSAcK IDNot Available
Chemspider ID388969
KEGG Compound IDC03196
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID5662
PubChem Compound439939
PDB IDS2G
ChEBI ID32797
References
Synthesis ReferenceKobayashi, Hidehiko; Yamaguchi, Koretaka; Yamashita, Takeshi. a-Hydroxyglutaric acid from glutamic acid. Jpn. Tokkyo Koho (1968), 3 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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 ]
  2. Gibson KM, ten Brink HJ, Schor DS, Kok RM, Bootsma AH, Hoffmann GF, Jakobs C: Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias. Pediatr Res. 1993 Sep;34(3):277-80. [PubMed:8134166 ]
  3. Rashed MS, AlAmoudi M, Aboul-Enein HY: Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of 2-hydroxyglutaric acid in urine. Biomed Chromatogr. 2000 Aug;14(5):317-20. [PubMed:10960831 ]
  4. Fujitake J, Ishikawa Y, Fujii H, Nishimura K, Hayakawa K, Inoue F, Terada N, Okochi M, Tatsuoka Y: L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family. J Neurol. 1999 May;246(5):378-82. [PubMed:10399870 ]
  5. Barth PG, Hoffmann GF, Jaeken J, Lehnert W, Hanefeld F, van Gennip AH, Duran M, Valk J, Schutgens RB, Trefz FK, et al.: L-2-hydroxyglutaric acidemia: a novel inherited neurometabolic disease. Ann Neurol. 1992 Jul;32(1):66-71. [PubMed:1642474 ]
  6. de Klerk JB, Huijmans JG, Stroink H, Robben SG, Jakobs C, Duran M: L-2-hydroxyglutaric aciduria: clinical heterogeneity versus biochemical homogeneity in a sibship. Neuropediatrics. 1997 Dec;28(6):314-7. [PubMed:9453028 ]

Enzymes

General function:
Involved in 2-hydroxyglutarate dehydrogenase activity
Specific function:
Not Available
Gene Name:
L2HGDH
Uniprot ID:
Q9H9P8
Molecular weight:
50315.58
Reactions
L-2-Hydroxyglutaric acid + acceptor → Oxoglutaric acid + reduced acceptordetails