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Human Metabolome Database Version 2.5

 

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

Legend: metabolite field enzyme field

Version 2.5
Creation Date 2005-11-16 15:48:42
Update Date 2009-07-03 11:07:23
Accession Number HMDB00606
Secondary Accession Numbers HMDB02323
Common Name D-2-Hydroxyglutaric acid
Description 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)
Synonyms
  1. (R)-2-Hydroxyglutarate
  2. (R)-2-Hydroxyglutaric acid
  3. (R)-2-hydroxy-Pentanedioate
  4. (R)-2-hydroxy-Pentanedioic acid
  5. (R)-a-Hydroxyglutarate
  6. (R)-a-Hydroxyglutaric acid
  7. 2-hydroxy-D-Glutarate
  8. 2-hydroxy-D-Glutaric acid
  9. D-2-Hydroxyglutarate
  10. D-2-Hydroxyglutaric acid
  11. D-a-Hydroxyglutarate
  12. D-a-Hydroxyglutaric acid
  13. (R)-alpha-Hydroxyglutarate
  14. (R)-alpha-Hydroxyglutaric acid
  15. 2-hydroxy-delta-Glutarate
  16. 2-hydroxy-delta-Glutaric acid
  17. delta-2-Hydroxyglutarate
  18. delta-2-Hydroxyglutaric acid
  19. delta-alpha-Hydroxyglutarate
  20. delta-alpha-Hydroxyglutaric acid
Chemical IUPAC Name 2-hydroxypentanedioic acid
Chemical Formula C5H8O5
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Organic acids
Class
  • Dicarboxylic Acids
Sub Class
  • Short chain dicarboxylic acids
Family
  • Mammalian Metabolite
Species
  • secondary alcohol
  • carboxylic acid
  • alpha-hydroxyacid
Biofunction
—
Application
—
Source
  • Endogenous
Average Molecular Weight 148.114
Monoisotopic Molecular Weight 148.037170
Isomeric SMILES O[C@H](CCC(O)=O)C(O)=O
Canonical SMILES OC(CCC(O)=O)C(O)=O
KEGG Compound ID C01087 Link Image
BioCyc ID Not Available
BiGG ID Not Available
Wikipedia Link Not Available
NuGOwiki Link HMDB00606 Link Image
Metagene Link HMDB00606 Link Image
METLIN ID 5581 Link Image
PubChem Compound 43 Link Image
PubChem Substance 828566 Link Image
ChEBI ID 32796 Link Image
CAS Registry Number 2889-31-8
InChI Identifier InChI=1/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m1/s1
Synthesis Reference Kobayashi, Hidehiko; Yamaguchi, Koretaka; Yamashita, Takeshi. a-Hydroxyglutaric acid from glutamic acid. Jpn. Tokkyo Koho (1968), 3 pp.
Melting Point (Experimental) >300 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 157.0 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge -2
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity -1.04 [Predicted by ALOGPS]; -1.1 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS)
MOL File Show
SDF File Show
PDB File Show
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Not Available
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Not Available
Predicted 1H NMR Spectrum Show Image
Show Peaklist
Predicted 13C NMR Spectrum Show Image
Show Peaklist
Mass Spectrum Not Available
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Cytoplasm (Predicted from LogP)
Biofluid Location
  • Blood
  • Cerebrospinal Fluid
  • Urine
Tissue Location Not Available
Concentrations (Normal)
Biofluid Blood
Value 0.7 +/- 0.2 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Blood
Value 0.6 (0.30-0.90) uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
Biofluid CSF
Value 0.2 (0.1-0.30) uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
Biofluid Urine
Value 51.9 (13.7-97.3) umol/mmol creatinine
Age Newborn:0-30 days old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 41.5 (14.6-150.3) umol/mmol creatinine
Age Infant:0-1 yr old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 12.4 (5.1-24.9) umol/mmol creatinine
Age Children:1-13 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 11.2 (4.6-33.6) umol/mmol creatinine
Age Adolescent:13-18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
  • 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 Link Image]
Biofluid Urine
Value 10.0 (3.0-17.0) umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
Biofluid Urine
Value 33.0 (20.0-46.0) umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments Not Available
References
Concentrations (Abnormal)
Biofluid Blood
Value 61.0 +/- 14.0 uM
Age Adult:>18 yrs old
Sex Both
Condition D-2-hydroxyglutaric aciduria
Comments Not Available
References
  • 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 Link Image]
Biofluid Blood
Value 67.5 (62.0-73.0) uM
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
Biofluid CSF
Value 25.0 uM
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
Biofluid Urine
Value 1238.5 (730.0-1747.0) umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Comments Not Available
References
Biofluid Urine
Value 2175.0 (50.0-4300.0) umol/mmol creatinine
Age Adult:>18 yrs old
Sex Both
Condition Glutaric acidemia type 2
Comments Not Available
References
Associated Disorders
Condition 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 Link Image]
Glutaric acidemia type 2
OMIM ID
  • 600721 Link Image (D-2-hydroxyglutaric aciduria)
  • 231680 Link Image (Glutaric acidemia type 2)
Pathways Not Available
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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
Metabolic Enzymes
  1. Alcohol dehydrogenase iron-containing 1
Enzyme 1 [top]
Enzyme 1 ID 9419
Enzyme 1 Name Alcohol dehydrogenase iron-containing 1
Enzyme 1 Synonyms Not Available
Enzyme 1 Gene Name ADHFE1
Enzyme 1 Protein Sequence >Alcohol dehydrogenase iron-containing 1 
MAAAARARVAYLLRQLQRAACQCPTHSHTYSQAPGLSPSGKTTDYAFEMAVSNIRYGAAV
TKEVGMDLKNMGAKNVCLMTDKNLSKLPPVQVAMDSLVKNGIPFTVYDNVRVEPTDSSFM
EAIEFAQKGAFDAYVAVGGGSTMDTCKAANLYASSPHSDFLDYVSAPIGKGKPVSVPLKP
LIAVPTTSGTGSETTGVAIFDYEHLKVKIGITSRAIKPTLGLIDPLHTLHMPARVVANSG
FDVLCHALESYTTLPYHLRSPCPSNPITRPAYQGSNPISDIWAIHALRIVAKYLKRAVRN
PDDLEARSHMHLASAFAGIGFGNAGVHLCHGMSYPISGLVKMYKAKDYNVDHPLVPHGLS
VVLTSPAVFTFTAQMFPERHLEMAEILGADTRTARIQDAGLVLADTLRKFLFDLDVDDGL
AAVGYSKADIPALVKGTLPQERVTKLAPCPQSEEDLAALFEASMKLY
Enzyme 1 Number of Residues 467
Enzyme 1 Molecular Weight 50308
Enzyme 1 Theoretical pI Not Available
Enzyme 1 GO Classification
Function
  • binding
  • catalytic activity
  • cation binding
  • ion binding
  • iron ion binding
  • oxidoreductase activity
  • transition metal ion binding
Process
  • metabolism
  • physiological process
Component
—
Enzyme 1 General Function Energy production and conversion
Enzyme 1 Specific Function Not Available
Enzyme 1 Pathways Not Available
Enzyme 1 Reactions
  • 3,4-Dihydroxymandelaldehyde + H+ + Nicotinamide adenine dinucleotide - reduced <==> 3,4-Dihydroxyphenylethyleneglycol + Nicotinamide adenine dinucleotide
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals
  • None
Enzyme 1 Transmembrane Regions
  • None
Enzyme 1 Essentiality Not Available
Enzyme 1 GenBank ID Protein 25989126 Link Image
Enzyme 1 UniProtKB/Swiss-Prot ID Q8IWW8 Link Image
Enzyme 1 UniProtKB/Swiss-Prot Entry Name Q8IWW8_HUMAN Link Image
Enzyme 1 PDB ID Not Available
Enzyme 1 Cellular Location Not Available
Enzyme 1 Gene Sequence Not Available
Enzyme 1 GenBank Gene ID AY033237 Link Image
Enzyme 1 GeneCard ID Not Available
Enzyme 1 GenAtlas ID ADHFE1 Link Image
Enzyme 1 HGNC ID HGNC:16354 Link Image
Enzyme 1 Chromosome Location Not Available
Enzyme 1 Locus Not Available
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 General References
  1. Deng Y, Wang Z, Gu S, Ji C, Ying K, Xie Y, Mao Y: Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1). DNA Seq. 2002 Oct;13(5):301-6. [PubMed Link Image]
Enzyme 1 Metabolite References Not Available