Human Metabolome Database Version 3.5

Showing metabocard for D-2-Hydroxyglutaric acid (HMDB00606)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:08:55 -0700
HMDB ID HMDB00606
Secondary Accession Numbers
  • HMDB02323
Metabolite Identification
Common Name D-2-Hydroxyglutaric acid
Description D-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 1.1.99.2) 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).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  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 Formula C5H8O5
Average Molecular Weight 148.114
Monoisotopic Molecular Weight 148.037173366
IUPAC Name (2R)-2-hydroxypentanedioic acid
Traditional IUPAC Name D-2-hydroxy-glutaric acid
CAS Registry Number 2889-31-8
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 Key HWXBTNAVRSUOJR-GSVOUGTGSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Organic Acids and Derivatives
Class Hydroxy Acids and Derivatives
Sub Class Alpha 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
Substituents
  • Carboxylic Acid
  • Secondary Alcohol
Direct Parent Alpha Hydroxy Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
  • Microbial
Biofunction Not Available
Application Not Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point > 300 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 157 g/L ALOGPS
LogP -1.04 ALOGPS
LogP -0.82 ChemAxon
LogS 0.03 ALOGPS
pKa (strongest acidic) 3.28 ChemAxon
pKa (strongest basic) -3.8 ChemAxon
Hydrogen Acceptor Count 5 ChemAxon
Hydrogen Donor Count 3 ChemAxon
Polar Surface Area 94.83 A2 ChemAxon
Rotatable Bond Count 4 ChemAxon
Refractivity 29.63 ChemAxon
Polarizability 12.97 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -2 ChemAxon
Spectra
Gas-MS Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location Not Available
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.6 (0.30-0.90) uM Adult (>18 years old) Both Normal
Blood Detected and Quantified
0.7 +/- 0.2 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
0.2 (0.1-0.30) uM Adult (>18 years old) Both Normal
Urine Detected and Quantified
11.2 (4.6-33.6) umol/mmol creatinine Adolescent (13-18 years old) Both Normal
Urine Detected and Quantified
33.0 (20.0-46.0) umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
10.0 (3.0-17.0) umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
51.9 (13.7-97.3) umol/mmol creatinine Newborn (0-30 days old) Both Normal
Urine Detected and Quantified
41.5 (14.6-150.3) umol/mmol creatinine Infant (0-1 year old) Both Normal
Urine Detected and Quantified
12.4 (5.1-24.9) umol/mmol creatinine Children (1-13 year old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 67.5 (62.0-73.0) uM Children (1-13 year old) Both 2-Hydroxyglutaric acid Aciduria (D)
Blood Detected and Quantified 61.0 +/- 14.0 uM Adult (>18 years old) Both D-2-Hydroxyglutaric aciduria
Cerebrospinal Fluid (CSF) Detected and Quantified 25.0 uM Children (1-13 year old) Both 2-Hydroxyglutaric Aciduria (D)
Urine Detected and Quantified 2175.0 (50.0-4300.0) umol/mmol creatinine Children (1-13 year old) Both Glutaric Aciduria II
Urine Detected and Quantified 1238.5 (730.0-1747.0) umol/mmol creatinine Children (1-13 year old) Both 2-Hydroxyglutaric Aciduria (D)
Associated Disorders and Diseases
Disease References
D-2-hydroxyglutaric aciduria
  • 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 Link_out
    Glutaric aciduria II
        Glutaric acidemia type 2
            Associated OMIM IDs
            DrugBank ID Not Available
            DrugBank Metabolite ID Not Available
            Phenol Explorer Compound ID Not Available
            Phenol Explorer Metabolite ID Not Available
            FoodDB ID FDB022139
            KNApSAcK ID Not Available
            Chemspider ID 388508 Link_out
            KEGG Compound ID C01087 Link_out
            BioCyc ID Not Available
            BiGG ID Not Available
            Wikipedia Link Not Available
            NuGOwiki Link HMDB00606 Link_out
            Metagene Link HMDB00606 Link_out
            METLIN ID 5581 Link_out
            PubChem Compound 439391 Link_out
            PDB ID 2HG Link_out
            ChEBI ID 32796 Link_out
            References
            Synthesis Reference Kobayashi, 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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out

            Enzymes
            Name: D-2-hydroxyglutarate dehydrogenase, mitochondrial
            Reactions:
            D-2-Hydroxyglutaric acid + acceptor unknown Oxoglutaric acid + reduced acceptor details
            Gene Name: D2HGDH
            Uniprot ID: Q8N465 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Hydroxyacid-oxoacid transhydrogenase, mitochondrial
            Reactions:
            (S)-3-Hydroxybutyric acid + Oxoglutaric acid unknown Acetoacetic acid + D-2-Hydroxyglutaric acid details
            4-Hydroxybutyric acid + Oxoglutaric acid unknown Succinic acid semialdehyde + D-2-Hydroxyglutaric acid details
            Gene Name: ADHFE1
            Uniprot ID: Q8IWW8 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA