ContaminantDB: D-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 06:03:49 UTC

Update Date

2026-04-06 11:40:09 UTC

Accession Number

CHEM003211

Identification

Common Name

D-2-Hydroxyglutaric acid

Class

Small Molecule

Description

D-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. D-2-Hydroxyglutarate is also formed via the normal activity of hydroxyacid-oxoacid transhydrogenase during conversion of 4-hydroxybutyrate to succinate semialdehyde. 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. D-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. D-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)

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
(R)-2-Hydroxyglutarate	ChEBI
(R)-Hydroxyglutarate	ChEBI
(R)-2-Hydroxyglutaric acid	Generator
(R)-Hydroxyglutaric acid	Generator
D-2-Hydroxyglutarate	Generator
(R)-2-Hydroxy-pentanedioate	HMDB
(R)-2-Hydroxy-pentanedioic acid	HMDB
(R)-a-Hydroxyglutarate	HMDB
(R)-a-Hydroxyglutaric acid	HMDB
(R)-alpha-Hydroxyglutarate	HMDB
(R)-alpha-Hydroxyglutaric acid	HMDB
2-Hydroxy-D-glutarate	HMDB
2-Hydroxy-D-glutaric acid	HMDB
2-Hydroxy-delta-glutarate	HMDB
2-Hydroxy-delta-glutaric acid	HMDB
D-a-Hydroxyglutarate	HMDB
D-a-Hydroxyglutaric acid	HMDB
delta-2-Hydroxyglutarate	HMDB
delta-2-Hydroxyglutaric acid	HMDB
delta-alpha-Hydroxyglutarate	HMDB
delta-alpha-Hydroxyglutaric acid	HMDB
2-Hydroxyglutarate	HMDB
alpha-Hydroxyglutarate, (D)-isomer	HMDB
alpha-Hydroxyglutarate, (DL)-isomer	HMDB
2-Hydroxyglutaric acid	HMDB
alpha-Hydroxyglutarate	HMDB
alpha-Hydroxyglutarate, (L)-isomer	HMDB
alpha-Hydroxyglutarate, disodium salt	HMDB

Chemical Formula

C₅H₈O₅

Average Molecular Mass

148.114 g/mol

Monoisotopic Mass

148.037 g/mol

CAS Registry Number

2889-31-8

IUPAC Name

(2R)-2-hydroxypentanedioic acid

Traditional Name

D-2-hydroxyglutaric acid

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

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:32796 )

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

metabolite

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	> 300°C
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	splash10-0zgl-9300000000-805667744aba36281cec	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-00gv-8191000000-f6fdffd87ffe1acf65b4	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 (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 (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
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001j-1900000000-dbf80fc2b86ec60d623e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0m5r-9600000000-d1bc7ce2206164b5bc2c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-df3e77cb42d6f7647a64	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-1900000000-095c1140772d4cdd149b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zfr-7900000000-ce158ac5b56eff867735	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9000000000-e30760384709aa978986	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
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
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

Toxicity Profile

Route of Exposure

Endogenous, Ingestion

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. High L-2-Hydroxyglutarate levels are associated with gliomas and acute myeloid leukemia. L-2-Hydroxyglutarate can reversibly promote leukemogenesis in vitro. D-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. D-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

2-hydroxyglutarate can be converted to α-ketoglutaric acid through the action of a 2-hydroxyglutarate dehydrogenase.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Not listed by IARC. Has been implicated in oncogenesis (8, 7, 6).

Uses/Sources

Not Available

Minimum Risk Level

Not Available

Health Effects

High 2-Hydroxyglutarate levels are associated with gliomas and acute myeloid leukemia. L-2-Hydroxyglutarate can reversibly promote leukemogenesis in vitro. Chronically high levels of L-2-hydroxyglutaric acid are associated with the inborn error of metabolism called: D-2-Hydroxyglutaric Aciduria. The D form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness.

Symptoms

Symptoms of chronic exposure to D-2-Hydroxyglutarate include macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness.

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0000606

FooDB ID