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Showing metabocard for L-2-Hydroxyglutaric acid (HMDB0000694)

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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2022-03-07 02:49:05 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, which is 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 ). In humans, 2-hydroxyglutarate is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria it is formed by a 2-hydroxyglutarate synthase. L-2-Hydroxyglutaric acid can be converted to alpha-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (EC 1.1.99.2). In humans, there are two such enzymes (D2HGDH and L2HGDH). Both the D and L stereoisomers of hydroxyglutaric acid are found in body fluids. L-2-Hydroxyglutaric acid can also be produced via gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of the TCA cycle and this compound is generated in high abundance when IDH is mutated. Since L-2-hydroxyglutaric acid is sufficiently similar in structure to 2-oxoglutarate (2OG), 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-inducible factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that L-2-hydroxyglutaric acid causes a cascading effect that leads genetic perturbations and malignant transformation. Depending on the circumstances, L-2-hydroxyglutaric acid can function as an oncometabolite, a neurotoxin, an acidogen, and a metabotoxin. An oncometabolite is a compound that promotes tumour growth and survival. A neurotoxin is compound that is toxic to neurons or neural tissue. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. As an oncometabolite, L-2-hydroxyglutaric acid is a competitive inhibitor of multiple alpha-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5mC hydroxylases. As a result, high levels of 2-hydroxyglutarate lead to genome-wide histone and DNA methylation alterations, which in turn lead to mutations that ultimately cause cancer (PMID: 29038145 ). As a neurotoxin, L-2-hydroxyglutaric acid mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. L-2-Hydroxyglutaric acid is structurally similar to the excitatory amino acid glutamate and stimulates neurodegeneration by mechanisms similar to glutamate, NMDA, or mitochondrial toxins (PMID: 12153528 ). As an acidogen, L-2-hydroxyglutaric acid is classified as an alpha hydroxy acid belonging to the general class of compounds known as organic acids. Chronically high levels of L-2-hydroxyglutaric acid are characteristic of the inborn error of metabolism called L-2-hydroxyglutaric aciduria. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, kidney abnormalities, liver damage, seizures, coma, and possibly death. These are the symptoms typical of untreated L-2-hydroxyglutaric aciduria. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Structure
Data?1582752149
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for HMDB0000694 (L-2-Hydroxyglutaric acid)


  Mrv1652305271900172D          

 10  9  0  0  0  0            999 V2000
 9998.6124 9997.7078    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
 9997.8979 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1831 9997.7078    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4684 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9995.7534 9997.7078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4684 9998.9448    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.3301 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.0437 9997.7078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.3301 9998.9448    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9998.6124 9996.8823    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  7  1  0  0  0  0
  1 10  1  1  0  0  0
  2  3  1  0  0  0  0
  3  4  1  0  0  0  0
  4  5  1  0  0  0  0
  4  6  2  0  0  0  0
  7  8  1  0  0  0  0
  7  9  2  0  0  0  0
M  END
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3D MOL for HMDB0000694 (L-2-Hydroxyglutaric acid)

HMDB0000694
     RDKit          3D
L-2-Hydroxyglutaric acid
 18 17  0  0  0  0  0  0  0  0999 V2000
    1.9977   -0.2899   -1.4646 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1686    0.1066   -0.3001 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4952    0.0307    0.1750 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.1853    0.6390    0.6379 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2303    0.6592    0.2044 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8392   -0.6798   -0.0787 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.2355   -1.4124   -1.0744 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3010   -0.5240   -0.4111 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7416   -1.0283   -1.4581 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0707    0.1863    0.4926 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6610   -0.4993    1.0067 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2910    0.0467    1.6018 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5412    1.6852    0.9006 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4219    1.3837   -0.6309 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8187    1.1009    1.0675 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8160   -1.3288    0.8399 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6126   -1.2382   -1.9753 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2525    1.1624    0.4668 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  6  8  1  0
  8  9  2  0
  8 10  1  0
  3 11  1  0
  4 12  1  0
  4 13  1  0
  5 14  1  0
  5 15  1  0
  6 16  1  1
  7 17  1  0
 10 18  1  0
M  END
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3D SDF for HMDB0000694 (L-2-Hydroxyglutaric acid)


  Mrv1652305271900172D          

 10  9  0  0  0  0            999 V2000
 9998.6124 9997.7078    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
 9997.8979 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1831 9997.7078    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4684 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9995.7534 9997.7078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4684 9998.9448    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.3301 9998.1199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.0437 9997.7078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.3301 9998.9448    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9998.6124 9996.8823    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  7  1  0  0  0  0
  1 10  1  1  0  0  0
  2  3  1  0  0  0  0
  3  4  1  0  0  0  0
  4  5  1  0  0  0  0
  4  6  2  0  0  0  0
  7  8  1  0  0  0  0
  7  9  2  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0000694

> <DATABASE_NAME>
hmdb

> <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-/m0/s1

> <INCHI_KEY>
HWXBTNAVRSUOJR-VKHMYHEASA-N

> <FORMULA>
C5H8O5

> <MOLECULAR_WEIGHT>
148.114

> <EXACT_MASS>
148.037173366

> <JCHEM_ACCEPTOR_COUNT>
5

> <JCHEM_ATOM_COUNT>
18

> <JCHEM_AVERAGE_POLARIZABILITY>
12.9730498807228

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
3

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
(2S)-2-hydroxypentanedioic acid

> <ALOGPS_LOGP>
-1.04

> <JCHEM_LOGP>
-0.824980223

> <ALOGPS_LOGS>
0.03

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
0

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-2

> <JCHEM_PKA>
4.159324461588801

> <JCHEM_PKA_STRONGEST_ACIDIC>
3.276485914460605

> <JCHEM_PKA_STRONGEST_BASIC>
-3.8068384384876675

> <JCHEM_POLAR_SURFACE_AREA>
94.83000000000001

> <JCHEM_REFRACTIVITY>
29.6302

> <JCHEM_ROTATABLE_BOND_COUNT>
4

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
1.57e+02 g/l

> <JCHEM_TRADITIONAL_IUPAC>
L-2-hydroxyglutaric acid

> <JCHEM_VEBER_RULE>
0

$$$$
Download

3D-SDF for HMDB0000694 (L-2-Hydroxyglutaric acid)

HMDB0000694
     RDKit          3D
L-2-Hydroxyglutaric acid
 18 17  0  0  0  0  0  0  0  0999 V2000
    1.9977   -0.2899   -1.4646 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1686    0.1066   -0.3001 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4952    0.0307    0.1750 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.1853    0.6390    0.6379 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2303    0.6592    0.2044 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8392   -0.6798   -0.0787 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.2355   -1.4124   -1.0744 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3010   -0.5240   -0.4111 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7416   -1.0283   -1.4581 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0707    0.1863    0.4926 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6610   -0.4993    1.0067 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2910    0.0467    1.6018 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5412    1.6852    0.9006 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4219    1.3837   -0.6309 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8187    1.1009    1.0675 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8160   -1.3288    0.8399 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6126   -1.2382   -1.9753 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2525    1.1624    0.4668 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  6  8  1  0
  8  9  2  0
  8 10  1  0
  3 11  1  0
  4 12  1  0
  4 13  1  0
  5 14  1  0
  5 15  1  0
  6 16  1  1
  7 17  1  0
 10 18  1  0
M  END
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PDB for HMDB0000694 (L-2-Hydroxyglutaric acid)

HEADER    PROTEIN                                 27-MAY-19   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   27-MAY-19         0                                  
HETATM    1  C   UNK     0    8664.0768662.388   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8662.7438663.157   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0    8661.4088662.388   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0    8660.0748663.157   0.000  0.00  0.00           C+0
HETATM    5  O   UNK     0    8658.7408662.388   0.000  0.00  0.00           O+0
HETATM    6  O   UNK     0    8660.0748664.697   0.000  0.00  0.00           O+0
HETATM    7  C   UNK     0    8665.4168663.157   0.000  0.00  0.00           C+0
HETATM    8  O   UNK     0    8666.7488662.388   0.000  0.00  0.00           O+0
HETATM    9  O   UNK     0    8665.4168664.697   0.000  0.00  0.00           O+0
HETATM   10  O   UNK     0    8664.0768660.847   0.000  0.00  0.00           O+0
CONECT    1    2    7   10                                                  
CONECT    2    1    3                                                       
CONECT    3    2    4                                                       
CONECT    4    3    5    6                                                  
CONECT    5    4                                                            
CONECT    6    4                                                            
CONECT    7    1    8    9                                                  
CONECT    8    7                                                            
CONECT    9    7                                                            
CONECT   10    1                                                            
MASTER        0    0    0    0    0    0    0    0   10    0   18    0
END
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3D PDB for HMDB0000694 (L-2-Hydroxyglutaric acid)

COMPND    HMDB0000694
HETATM    1  O1  UNL     1       1.998  -0.290  -1.465  1.00  0.00           O  
HETATM    2  C1  UNL     1       2.169   0.107  -0.300  1.00  0.00           C  
HETATM    3  O2  UNL     1       3.495   0.031   0.175  1.00  0.00           O  
HETATM    4  C2  UNL     1       1.185   0.639   0.638  1.00  0.00           C  
HETATM    5  C3  UNL     1      -0.230   0.659   0.204  1.00  0.00           C  
HETATM    6  C4  UNL     1      -0.839  -0.680  -0.079  1.00  0.00           C  
HETATM    7  O3  UNL     1      -0.235  -1.412  -1.074  1.00  0.00           O  
HETATM    8  C5  UNL     1      -2.301  -0.524  -0.411  1.00  0.00           C  
HETATM    9  O4  UNL     1      -2.742  -1.028  -1.458  1.00  0.00           O  
HETATM   10  O5  UNL     1      -3.071   0.186   0.493  1.00  0.00           O  
HETATM   11  H1  UNL     1       3.661  -0.499   1.007  1.00  0.00           H  
HETATM   12  H2  UNL     1       1.291   0.047   1.602  1.00  0.00           H  
HETATM   13  H3  UNL     1       1.541   1.685   0.901  1.00  0.00           H  
HETATM   14  H4  UNL     1      -0.422   1.384  -0.631  1.00  0.00           H  
HETATM   15  H5  UNL     1      -0.819   1.101   1.067  1.00  0.00           H  
HETATM   16  H6  UNL     1      -0.816  -1.329   0.840  1.00  0.00           H  
HETATM   17  H7  UNL     1      -0.613  -1.238  -1.975  1.00  0.00           H  
HETATM   18  H8  UNL     1      -3.253   1.162   0.467  1.00  0.00           H  
CONECT    1    2    2
CONECT    2    3    4
CONECT    3   11
CONECT    4    5   12   13
CONECT    5    6   14   15
CONECT    6    7    8   16
CONECT    7   17
CONECT    8    9    9   10
CONECT   10   18
END
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SMILES for HMDB0000694 (L-2-Hydroxyglutaric acid)

O[C@@H](CCC(O)=O)C(O)=O
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INCHI for HMDB0000694 (L-2-Hydroxyglutaric acid)

InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m0/s1
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View in JSmolView NMR AssignmentsView Stereo Labels
Synonyms
ValueSource
(S)-2-HydroxyglutarateChEBI
(S)-2-Hydroxyglutaric acidGenerator
L-2-HydroxyglutarateGenerator
(S)-Α-hydroxyglutarateHMDB
(S)-Α-hydroxyglutaric acidHMDB
(S)-alpha-HydroxyglutarateHMDB
(S)-alpha-Hydroxyglutaric acidHMDB
2-Hydroxy-(S)-pentanedioateHMDB
2-Hydroxy-(S)-pentanedioic acidHMDB
2-Hydroxy-L-glutarateHMDB
2-Hydroxy-L-glutaric acidHMDB
L-Α-hydroxyglutarateHMDB
L-Α-hydroxyglutaric acidHMDB
L-alpha-HydroxyglutarateHMDB
L-alpha-Hydroxyglutaric acidHMDB
L-2-Hydroxyglutaric acidHMDB
Chemical FormulaC5H8O5
Average Molecular Weight148.114
Monoisotopic Molecular Weight148.037173366
IUPAC Name(2S)-2-hydroxypentanedioic acid
Traditional NameL-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-/m0/s1
InChI KeyHWXBTNAVRSUOJR-VKHMYHEASA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as short-chain hydroxy acids and derivatives. These are hydroxy acids with an alkyl chain the contains less than 6 carbon atoms.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassHydroxy acids and derivatives
Sub ClassShort-chain hydroxy 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
Disposition
Biological locationRoute of exposureSource
Process
Naturally occurring process
Role
Indirect biological roleBiological roleIndustrial application
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M-H]-Not Available119.063http://allccs.zhulab.cn/database/detail?ID=AllCCS00000025
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
AllCCS[M+H]+134.03432859911
AllCCS[M-H]-126.53232859911
DeepCCS[M+H]+127.20130932474
DeepCCS[M-H]-123.33930932474
DeepCCS[M-2H]-160.84330932474
DeepCCS[M+Na]+136.25230932474
AllCCS[M+H]+134.032859911
AllCCS[M+H-H2O]+130.032859911
AllCCS[M+NH4]+137.832859911
AllCCS[M+Na]+138.932859911
AllCCS[M-H]-126.532859911
AllCCS[M+Na-2H]-128.732859911
AllCCS[M+HCOO]-131.132859911

Predicted Retention Times

Underivatized

Chromatographic MethodRetention TimeReference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.5.74 minutes32390414
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.1.53 minutes32390414
Predicted by Siyang on May 30, 20229.4449 minutes33406817
Predicted by Siyang using ReTip algorithm on June 8, 20223.03 minutes32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid265.5 seconds40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid773.8 seconds40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid329.8 seconds40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid55.1 seconds40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid191.3 seconds40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid66.7 seconds40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid262.2 seconds40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid251.6 seconds40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)453.3 seconds40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid603.0 seconds40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid76.9 seconds40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid825.9 seconds40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid207.7 seconds40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid217.5 seconds40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate720.0 seconds40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA286.7 seconds40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water462.6 seconds40023050

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
L-2-Hydroxyglutaric acidO[C@@H](CCC(O)=O)C(O)=O2340.9Standard polar33892256
L-2-Hydroxyglutaric acidO[C@@H](CCC(O)=O)C(O)=O1100.2Standard non polar33892256
L-2-Hydroxyglutaric acidO[C@@H](CCC(O)=O)C(O)=O1428.9Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
L-2-Hydroxyglutaric acid,1TMS,isomer #1C[Si](C)(C)O[C@@H](CCC(=O)O)C(=O)O1441.3Semi standard non polar33892256
L-2-Hydroxyglutaric acid,1TMS,isomer #2C[Si](C)(C)OC(=O)CC[C@H](O)C(=O)O1442.3Semi standard non polar33892256
L-2-Hydroxyglutaric acid,1TMS,isomer #3C[Si](C)(C)OC(=O)[C@@H](O)CCC(=O)O1400.3Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TMS,isomer #1C[Si](C)(C)OC(=O)CC[C@H](O[Si](C)(C)C)C(=O)O1536.2Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TMS,isomer #2C[Si](C)(C)OC(=O)[C@H](CCC(=O)O)O[Si](C)(C)C1504.0Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TMS,isomer #3C[Si](C)(C)OC(=O)CC[C@H](O)C(=O)O[Si](C)(C)C1476.7Semi standard non polar33892256
L-2-Hydroxyglutaric acid,3TMS,isomer #1C[Si](C)(C)OC(=O)CC[C@H](O[Si](C)(C)C)C(=O)O[Si](C)(C)C1584.8Semi standard non polar33892256
L-2-Hydroxyglutaric acid,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)O[C@@H](CCC(=O)O)C(=O)O1698.7Semi standard non polar33892256
L-2-Hydroxyglutaric acid,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC(=O)CC[C@H](O)C(=O)O1702.2Semi standard non polar33892256
L-2-Hydroxyglutaric acid,1TBDMS,isomer #3CC(C)(C)[Si](C)(C)OC(=O)[C@@H](O)CCC(=O)O1672.0Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC(=O)CC[C@H](O[Si](C)(C)C(C)(C)C)C(=O)O1992.1Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC(=O)[C@H](CCC(=O)O)O[Si](C)(C)C(C)(C)C1979.7Semi standard non polar33892256
L-2-Hydroxyglutaric acid,2TBDMS,isomer #3CC(C)(C)[Si](C)(C)OC(=O)CC[C@H](O)C(=O)O[Si](C)(C)C(C)(C)C1935.0Semi standard non polar33892256
L-2-Hydroxyglutaric acid,3TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC(=O)CC[C@H](O[Si](C)(C)C(C)(C)C)C(=O)O[Si](C)(C)C(C)(C)C2222.5Semi standard non polar33892256
Spectra
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
  • Mitochondria
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.6(0.5-1.0) uMInfant (0-1 year old)FemaleNormal details
BloodDetected and Quantified0.5-1.0 uMInfant (0-1 year old)BothNormal details
BloodDetected and Quantified0 uMChildren (1 - 13 years old)BothNormal details
BloodDetected and Quantified1.5 (0.0-1.5) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.3-2.3 uMInfant (0-1 year old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.7(0.3-2.3) uMInfant (0-1 year old)FemaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.0 +/- 1.0 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1 uMChildren (1-13 years old)BothNormal details
FecesDetected but not QuantifiedNot QuantifiedNot SpecifiedNot Specified
Normal		 details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal		 details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
    • Zerihun T. Dame, ...
 details
UrineDetected and Quantified1.3-19 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified<2.5 umol/mmol creatinineAdolescent (13-18 years old)MaleNormal details
UrineDetected and Quantified6(1.3-19) umol/mmol creatinineInfant (0-1 year old)FemaleNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected and Quantified24.379 +/- 9.126 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Analysis of 30 no...
 details
UrineDetected and Quantified<26.15 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
 details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal		 details
UrineDetected and Quantified33.0 (13.3-77.9) umol/mmol creatinineAdult (>18 years old)Both
Normal		 details
UrineDetected and Quantified2.2 (0.8-52) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified11.2 (4.6-33.6) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified12.4 (5.1-24.9) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified41.5 (14.6-150.3) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified51.9 (13.7-97.3) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified47.0 +/- 13.0 uMAdult (>18 years old)BothL-2-hydroxyglutaric aciduria details
BloodDetected and Quantified23 uMAdolescent (13-18 years old)MaleL-2-hydroxyglutaric aciduria details
BloodDetected and Quantified2.0(1.1-3.0) uMInfant (0-1 year old)BothCombined D,L-2-hydroxyglutaric aciduria details
BloodDetected and Quantified47(27-62) uMInfant (0-1 year old)FemaleL-2-Hydroxyglutaric aciduria details
Cerebrospinal Fluid (CSF)Detected and Quantified30 uMAdolescent (13-18 years old)MaleL-2-hydroxyglutaric aciduria details
Cerebrospinal Fluid (CSF)Detected and Quantified62 (34-100) uMInfant (0-1 year old)FemaleL-2-Hydroxyglutaric aciduria details
UrineDetected and Quantified61.074 +/- 36.982 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Analysis of 30 no...
 details
UrineDetected and Quantified32 umol/mmol creatinineInfant (0-1 year old)FemaleD,L-2-Hydroxyglutaric aciduria details
UrineDetected and Quantified60 umol/mmol creatinineInfant (0-1 year old)Female
D2-/L2-hydroxyglutaric aciduria		 details
UrineDetected and Quantified122 umol/mmol creatinineInfant (0-1 year old)FemaleD2-/L2-hydroxyglutaric aciduria details
UrineDetected and Quantified942 umol/mmol creatinineAdolescent (13-18 years old)MaleL-2-hydroxyglutaric aciduria details
UrineDetected and Quantified161(64-247) umol/mmol creatinineInfant (0-1 year old)BothCombined D,L-2-hydroxyglutaric aciduria details
UrineDetected and Quantified76-83 umol/mmol creatinineInfant (0-1 year old)MaleD-2-hydroxyglutaric aciduria details
UrineDetected and Quantified145 umol/mmol creatinineChildren (1-13 years old)Male
D, L-2-hydroxyglutaric aciduria		 details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Bladder cancer		 details
Associated Disorders and Diseases
Disease References
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 ]
  2. Seijo-Martinez M, Navarro C, Castro del Rio M, Vila O, Puig M, Ribes A, Butron M: L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings. Arch Neurol. 2005 Apr;62(4):666-70. [PubMed:15824270 ]
  3. Gibson KM, Craigen W, Herman GE, Jakobs C: D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? J Inherit Metab Dis. 1993;16(3):497-500. [PubMed:7609436 ]
  4. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
D, L-2-hydroxyglutaric aciduria
  1. Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C: Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-87. doi: 10.1007/s10545-012-9462-5. Epub 2012 Mar 6. [PubMed:22391998 ]
  2. Gibson KM, Craigen W, Herman GE, Jakobs C: D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? J Inherit Metab Dis. 1993;16(3):497-500. [PubMed:7609436 ]
  3. Muntau AC, Roschinger W, Merkenschlager A, van der Knaap MS, Jakobs C, Duran M, Hoffmann GF, Roscher AA: Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria? Neuropediatrics. 2000 Jun;31(3):137-40. doi: 10.1055/s-2000-7497. [PubMed:10963100 ]
  4. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Eosinophilic esophagitis
  1. Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work). NA.
D-2-hydroxyglutaric aciduria
  1. Wajne M, Vargas CR, Funayama C, Fernandez A, Elias ML, Goodman SI, Jakobs C, van der Knaap MS: D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings. J Inherit Metab Dis. 2002 Feb;25(1):28-34. [PubMed:11999977 ]
Associated OMIM IDs
  • 236792 (L-2-Hydroxyglutaric aciduria)
  • 615182 (D, L-2-hydroxyglutaric aciduria)
  • 610247 (Eosinophilic esophagitis)
  • 600721 (D-2-hydroxyglutaric aciduria)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022185
KNApSAcK IDNot Available
Chemspider ID388969
KEGG Compound IDC03196
BioCyc IDCPD-381
BiGG IDNot Available
Wikipedia LinkAlpha-Hydroxyglutaric acid
METLIN IDNot Available
PubChem Compound439939
PDB IDNot Available
ChEBI ID32797
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000222
Good Scents IDNot Available
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 ]
  7. Collins RRJ, Patel K, Putnam WC, Kapur P, Rakheja D: Oncometabolites: A New Paradigm for Oncology, Metabolism, and the Clinical Laboratory. Clin Chem. 2017 Dec;63(12):1812-1820. doi: 10.1373/clinchem.2016.267666. Epub 2017 Oct 16. [PubMed:29038145 ]
  8. Kolker S, Pawlak V, Ahlemeyer B, Okun JG, Horster F, Mayatepek E, Krieglstein J, Hoffmann GF, Kohr G: NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria. Eur J Neurosci. 2002 Jul;16(1):21-8. [PubMed:12153528 ]

Enzymes

Enzyme Details
1. L-2-hydroxyglutarate dehydrogenase, mitochondrial
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