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Record Information
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:08:55 UTC
Secondary Accession Numbers
  • HMDB02323
Metabolite Identification
Common NameD-2-Hydroxyglutaric acid
DescriptionD-2-Hydroxyglutaric acid is related to neurometabolic disorder. Tissue accumulation of high amounts of D 2 hydroxyglutaric acid is the biochemical hallmark of the inherited neurometabolic disorder D 2 hydroxyglutaric aciduria. Both the D and the L stereoisomers of hydroxyglutaric acid (EC are found in body fluids. Accumulation of L-2-hydroxyglutaric acid 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 (see 236792). Nyhan et al. (1995) described 3 female patients, 2 of them sibs, who were found to have excess accumulation of D-2-hydroxyglutaric acid in the urine. The phenotype was quite variable, even among the sibs, but included mental retardation, macrocephaly with cerebral atrophy, hypotonia, seizures, and involuntary movements. One of the patients developed severe intermittent vomiting and was given a pyloromyotomy. The electroencephalogram demonstrated hypsarrhythmia. There was an increased concentration of protein in cerebrospinal fluid, an unusual finding in inborn errors of metabolism. Increased CSF protein has also been observed in mitochondrial disorders, peroxisomal disorders, and Krabbe disease. (OMIM #600721).
  1. (R)-2-hydroxy-Pentanedioate
  2. (R)-2-hydroxy-Pentanedioic acid
  3. (R)-2-Hydroxyglutarate
  4. (R)-2-Hydroxyglutaric acid
  5. (R)-a-Hydroxyglutarate
  6. (R)-a-Hydroxyglutaric acid
  7. (R)-alpha-Hydroxyglutarate
  8. (R)-alpha-Hydroxyglutaric acid
  9. 2-Hydroxy-D-Glutarate
  10. 2-Hydroxy-D-Glutaric acid
  11. 2-Hydroxy-delta-Glutarate
  12. 2-Hydroxy-delta-Glutaric acid
  13. D-2-Hydroxyglutarate
  14. D-2-Hydroxyglutaric acid
  15. D-a-Hydroxyglutarate
  16. D-a-Hydroxyglutaric acid
  17. delta-2-Hydroxyglutarate
  18. delta-2-Hydroxyglutaric acid
  19. delta-alpha-Hydroxyglutarate
  20. delta-alpha-Hydroxyglutaric acid
Chemical FormulaC5H8O5
Average Molecular Weight148.114
Monoisotopic Molecular Weight148.037173366
IUPAC Name(2R)-2-hydroxypentanedioic acid
Traditional NameD-2-hydroxy-glutaric acid
CAS Registry Number2889-31-8
InChI Identifier
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassOrganic Acids and Derivatives
ClassHydroxy Acids and Derivatives
Sub ClassAlpha Hydroxy Acids and Derivatives
Other Descriptors
  • 2-hydroxyglutaric acid(ChEBI)
  • Aliphatic Acyclic Compounds
  • Dicarboxylic Acids and Derivatives
  • Fatty Acids and Conjugates
  • Short-chain Hydroxy Acids and Derivatives
  • Carboxylic Acid
  • Secondary Alcohol
Direct ParentAlpha Hydroxy Acids and Derivatives
StatusDetected and Quantified
  • Endogenous
  • Microbial
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
Experimental Properties
Melting Point> 300 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility157 g/LALOGPS
pKa (Strongest Acidic)3.28ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83ChemAxon
Rotatable Bond Count4ChemAxon
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BloodDetected and Quantified0.6 (0.30-0.90) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.7 +/- 0.2 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.2 (0.1-0.30) uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified11.2 (4.6-33.6) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified33.0 (20.0-46.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified10.0 (3.0-17.0) umol/mmol creatinineAdult (>18 years old)BothNormal 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 and Quantified12.4 (5.1-24.9) umol/mmol creatinineChildren (1-13 years old)BothNormal details
Abnormal Concentrations
BloodDetected and Quantified67.5 (62.0-73.0) uMChildren (1-13 years old)Both2-Hydroxyglutaric Aciduria (D) details
BloodDetected and Quantified61.0 +/- 14.0 uMAdult (>18 years old)BothD-2-Hydroxyglutaric aciduria details
Cerebrospinal Fluid (CSF)Detected and Quantified25.0 uMChildren (1-13 years old)Both2-Hydroxyglutaric Aciduria (D) details
UrineDetected and Quantified2175.0 (50.0-4300.0) umol/mmol creatinineChildren (1-13 years old)BothGlutaric Aciduria II details
UrineDetected and Quantified1238.5 (730.0-1747.0) umol/mmol creatinineChildren (1-13 years old)Both2-Hydroxyglutaric Aciduria (D) details
Associated Disorders and Diseases
Disease References
D-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
  2. MetaGene
  3. MetaGene
Glutaric acidemia type 2
  1. MetaGene
Glutaric aciduria II
  1. MetaGene
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022139
KNApSAcK IDNot Available
Chemspider ID388508
KEGG Compound IDC01087
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00606
Metagene LinkHMDB00606
PubChem Compound439391
ChEBI ID32796
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. 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
  2. van der Knaap MS, Jakobs C, Hoffmann GF, Nyhan WL, Renier WO, Smeitink JA, Catsman-Berrevoets CE, Hjalmarson O, Vallance H, Sugita K, Bowe CM, Herrin JT, Craigen WJ, Buist NR, Brookfield DS, Chalmers RA: D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? Ann Neurol. 1999 Jan;45(1):111-9. Pubmed: 9894884
  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. da Silva CG, Bueno AR, Schuck PF, Leipnitz G, Ribeiro CA, Wannmacher CM, Wyse AT, Wajner M: D-2-hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats. Eur J Clin Invest. 2003 Oct;33(10):840-7. Pubmed: 14511354
  5. Clarke NF, Andrews I, Carpenter K, Jakobs C, van der Knaap MS, Kirk EP: D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. Am J Med Genet A. 2003 Aug 1;120(4):523-7. Pubmed: 12884432


General function:
Involved in catalytic activity
Specific function:
Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate.
Gene Name:
Uniprot ID:
Molecular weight:
D-2-Hydroxyglutaric acid + acceptor → Oxoglutaric acid + reduced acceptordetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.
Gene Name:
Uniprot ID:
Molecular weight:
(S)-3-Hydroxybutyric acid + Oxoglutaric acid → Acetoacetic acid + D-2-Hydroxyglutaric aciddetails
4-Hydroxybutyric acid + Oxoglutaric acid → Succinic acid semialdehyde + D-2-Hydroxyglutaric aciddetails