Livestock Metabolome Database: Showing metabocard for D-2-Hydroxyglutaric acid (LMDB00189)

Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References XML

Record Information

Version

1.0

Creation Date

2016-07-13 19:44:18 UTC

Update Date

2016-07-20 20:57:29 UTC

Lmdb

LMDB00189

Secondary Accession Numbers

None

Metabolite Identification

Common Name

D-2-Hydroxyglutaric acid

Description

D-2-Hydroxyglutaric acid is a biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria. D-2-hydroxyglutaric aciduria (caused by loss of D2HGDH or gain of function of IDH) is rare, with symptoms including cancer, macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. An elevated urine level of D-2-hydroxyglutarate has been reported patient with spondyloenchondrodysplasia (OMIM 271550 ). D-2-hydroxyglutarate can be converted to ?-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (D2HGDH). Additionally, the enzyme D-3-phosphoglycerate dehydrogenase (PHGDH) can catalyze the NADH-dependent reduction of ?-ketoglutarate (AKG) to D-2-hydroxyglutarate (D-2HG). 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 (OMIM 600721 ). D-2-Hydroxyglutaric acid is also considered to be an oncometabolite (or cancer-causing metabolite). It can be produced via gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of TCA cycle and this compound is generated in high abundance when IDH is mutated. D-2-hydroxyglutarate is sufficiently similar in structure to 2-oxogluratate (2OG) that 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 induced factor (HIF)-mediated hypoxic response and alterations in gene expression through global epigenetic remodeling. The net effect is that D-2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation.

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 Weight

148.114

Monoisotopic Molecular Weight

148.037173366

IUPAC Name

(2R)-2-hydroxypentanedioic acid

Traditional Name

D-2-hydroxyglutaric 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

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 )

Ontology

Status

Detected but not Quantified

Origin

Not Available

Biofunction

Not Available

Application

Not Available

Cellular locations

Not Available

Physical Properties

State

Not Available

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
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	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	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