ContaminantDB: L-2-Hydroxyglutaric acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (16)XML

Record Information

Version

1.0

Creation Date

2014-08-29 06:03:11 UTC

Update Date

2026-04-06 11:40:12 UTC

Accession Number

CHEM003207

Identification

Common Name

L-2-Hydroxyglutaric acid

Class

Small Molecule

Description

L-2-Hydroxyglutaric acid is an alpha hydroxy acid. In humans the compound is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria is formed by a 2-hydroxyglutarate synthase. The compound can be converted to α-ketoglutaric acid through the action of a 2-hydroxyglutarate dehydrogenase. In humans, there are two such enzymes called D2HGDH and L2HGDH. 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. Patients who have excess accumulation of D-2-hydroxyglutaric acid in the urine exhibit a variable phenotype but included mental retardation, macrocephaly with cerebral atrophy, hypotonia, seizures, and involuntary movements.

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Feces
HMDB Contaminants - Urine
T3DB toxins

Contaminant Type

Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
(S)-2-Hydroxyglutarate	ChEBI
(S)-2-Hydroxyglutaric acid	Generator
L-2-Hydroxyglutarate	Generator
(S)-Α-hydroxyglutarate	HMDB
(S)-Α-hydroxyglutaric acid	HMDB
(S)-alpha-Hydroxyglutarate	HMDB
(S)-alpha-Hydroxyglutaric acid	HMDB
2-Hydroxy-(S)-pentanedioate	HMDB
2-Hydroxy-(S)-pentanedioic acid	HMDB
2-Hydroxy-L-glutarate	HMDB
2-Hydroxy-L-glutaric acid	HMDB
L-Α-hydroxyglutarate	HMDB
L-Α-hydroxyglutaric acid	HMDB
L-alpha-Hydroxyglutarate	HMDB
L-alpha-Hydroxyglutaric acid	HMDB
L-2-Hydroxyglutaric acid	HMDB

Chemical Formula

C₅H₈O₅

Average Molecular Mass

148.114 g/mol

Monoisotopic Mass

148.037 g/mol

CAS Registry Number

13095-48-2

IUPAC Name

(2S)-2-hydroxypentanedioic acid

Traditional Name

L-2-hydroxyglutaric acid

SMILES

[H][C@](O)(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

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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Hydroxy acids and derivatives

Sub Class

Short-chain hydroxy acids and derivatives

Direct Parent

Short-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 Framework

Aliphatic acyclic compounds

External Descriptors

2-hydroxyglutaric acid (CHEBI:32797 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
2-Hydroxyglutric Aciduria (D And L Form)	SMP00136	Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	157 g/L	ALOGPS
logP	-1	ALOGPS
logP	-0.82	ChemAxon
logS	0.03	ALOGPS
pKa (Strongest Acidic)	3.28	ChemAxon
pKa (Strongest Basic)	-3.8	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	94.83 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	29.63 m³·mol⁻¹	ChemAxon
Polarizability	12.97 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_3_1) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-05mk-1900000000-c8b7818c2a1224f0b694	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-000i-9000000000-fc923f875e23e766078c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9000000000-9fb296154571d7ea7d13	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-9400000000-821ae25c1b9ac04003b7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-004i-3900000000-dc8454bb187902d1a08b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-1900000000-68ac8b23cf0ed0cf09f5	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0m5r-9600000000-fb8fb6611cf2b1bca9f7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-4912ecf3489ec68e9641	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-002b-0900000000-116ef9fca434a654a8f9	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zi9-5900000000-76cefbf1a7e32ce74bef	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9000000000-c4562468d1b81effdb63	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0w39-4900000000-1385b471f7cdf14ca14d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052r-9500000000-17ece6956644d4cf2069	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4r-9000000000-dbb4195080bddb5f6210	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0fbi-3900000000-f88fcf3ac0dd06636b16	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0k9i-9400000000-31bf8d3bb7203e7bf200	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4u-9000000000-c0ac45c4d66178ac20cf	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Endogenous, Injection

Mechanism of Toxicity

2-hydroxyglutarate is an oncometabolite. It is a competitive inhibitor of multiple α-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (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. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. L-2-hydroxyglutarate is structurally similar to the excitatory amino acid glutamate and stimulates neurodegeneration by mechanisms well-known for glutamate, NMDA or mitochondrial toxins (9).

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Not listed by IARC. Has been implicated in oncogenesis (8, 7).

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of L-2-hydroxyglutaric acid are associated with the inborn error of metabolism called: 2-Hydroxyglutaric Aciduria. L-2-hydroxyglutarate is neurotoxic. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. Symptoms of L-2-Hydroxyglutaric Aciduria include hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.

Symptoms

Chronic exposure of high levels of L-2-hydroxyglutarate leads to hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0000694

FooDB ID

FDB022185

Phenol Explorer ID