Livestock Metabolome Database: Showing metabocard for 2-Hydroxyglutarate (LMDB00702)

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

Record Information

Version

1.0

Creation Date

2016-07-13 19:55:48 UTC

Update Date

2016-09-23 18:45:41 UTC

Lmdb

LMDB00702

Secondary Accession Numbers

None

Metabolite Identification

Common Name

2-Hydroxyglutarate

Description

2-Hydroxyglutarate exists in 2 isomers: L-2-hydroxyglutarate acid and D-2-hydroxyglutarate. Both the D and the L stereoisomers of hydroxyglutaric acid (EC 1.1.99.2) are found in body fluids. In animals it is part of butanoate metabolic pathway and can be produced by phosphoglycerate dehydrogenase (PHGDH). More specifically, the enzyme PHGDH catalyzes the NADH-dependent reduction of ?-ketoglutarate (AKG) to D-2-hydroxyglutarate (D-2HG). 2-hydroxyglutarate is also the product of gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). Additionally, 2-hydroxyglutarate can be converted to ?-ketoglutaric acid through the action of 2-hydroxyglutarate dehydrogenase (HGDH). Humans have to variants of this enzyme: D-2-hydroxyglutarate dehydrogenase (D2HGDH) and L-2-hydroxyglutarate dehydrogenase (L2HGDH). A deficiency in either of these two enzymes can lead to a disease known as 2-hydroxyglutaric aciduria. L-2-hydroxyglutaric aciduria (caused by loss of L2HGDH) is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression. 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. 2-hydroxyglutarate was the first oncometabolite (or cancer-causing metabolite) to be formally named or identified. In cancer it is either produced by overexpression of phosphoglycerate dehydrogenase (PHGDH) or is produced in excess by gain-of-function mutations in the cytosolic and mitochondrial isoforms of isocitrate dehydrogenase (IDH). IDH is part of TCA cycle and is generated in high abundance when IDH is mutated. 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 2-hydroxyglutarate causes a cascading effect that leads genetic perturbations and malignant transformation.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
alpha-Hydroxyglutaric acid	ChEBI
alpha-Hydroxyglutarate	Kegg
a-Hydroxyglutarate	Generator
a-Hydroxyglutaric acid	Generator
Α-hydroxyglutarate	Generator
Α-hydroxyglutaric acid	Generator
2-Hydroxyglutaric acid	Generator
D-2-Hydroxyglutarate	HMDB
alpha-Hydroxyglutarate, (D)-isomer	HMDB
alpha-Hydroxyglutarate, (DL)-isomer	HMDB
alpha-Hydroxyglutarate, (L)-isomer	HMDB
alpha-Hydroxyglutarate, disodium salt	HMDB
(±)-2-hydroxyglutaric acid	HMDB
2,3-Dideoxypentaric acid	HMDB
2-Hydroxypentanedioic acid	HMDB
DL-2-Hydroxyglutaric acid	HMDB
2-Hydroxyglutarate	Generator

Chemical Formula

C₅H₈O₅

Average Molecular Weight

148.114

Monoisotopic Molecular Weight

148.037173366

IUPAC Name

2-hydroxypentanedioic acid

Traditional Name

2-hydroxyglutaric acid

CAS Registry Number

Not Available

SMILES

OC(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)

InChI Key

HWXBTNAVRSUOJR-UHFFFAOYSA-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-hydroxydicarboxylic acid (CHEBI:17084 )

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	splash10-0uel-9300000000-fbe125fbbc3b5bc0783b	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
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 0V, negative	splash10-0002-0900000000-09163ea46c418972472c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-0002-0900000000-d04b995445fdf4b9a53d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-0002-0900000000-b0a25d5d220611188e25	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-0002-0900000000-fffbc099f0f67f0511f3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-0002-0900000000-09f10084fba5e519de0a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-002b-0900000000-dff435b3dcd956320479	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, negative	splash10-004j-0900000000-bda2b170e24c7a9e5c35	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, negative	splash10-004i-0900000000-73ae87a8fb9bc7ee539d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 4V, negative	splash10-0fb9-1900000000-b1dc0a848bf8324490a7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 5V, negative	splash10-0ug0-3900000000-07793b211b4728e17669	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 6V, negative	splash10-0udr-6900000000-f034f6e5155f6da3db5a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 10V, negative	splash10-004i-0900000000-80c3e765d7538561ccbf	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 10V, negative	splash10-000i-9300000000-7ffbc20d629772e358cc	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-004i-0900000000-982cc580a7d58e352fcb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-004i-1900000000-5920ffef63672e32cc73	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-004i-2900000000-0945bfdbb47d1208ca55	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-004r-3900000000-8a092cb937763eb031bb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, negative	splash10-004r-6900000000-41fa2c2ee20825e5b11d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 4V, negative	splash10-002r-9800000000-6677f366953c5f35a17b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 4V, negative	splash10-000i-9500000000-0ca597332561395d2cc3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 5V, negative	splash10-000i-9400000000-510a9566cf27424fa58c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 10V, negative	splash10-0udr-4900000000-cf48fcc4c8561ba5a0e0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF 35V, positive	splash10-00di-9000000000-36768b96f759cfee016d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 10V, positive	splash10-0udi-0900000000-47e5cb48d7b683b18747	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, positive	splash10-03dj-1790000000-8eb0579a5917747d340e	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

Biological Properties

Cellular Locations

Not Available

Biofluid Locations and Tissue Locations

Milk

Concentrations

Biofluid	Status	Value	Condition	Species	Reference	Details
Milk	Detected but not Quantified	Not Applicable	Not Available	Bovine	25108860	details

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0059655

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

2-HYDROXYGLUTARIC_ACID

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Alpha-Hydroxyglutaric_acid

Chemspider ID

ChEBI ID

17084

PubChem Compound ID

Kegg Compound ID

C02630

YMDB ID

YMDB00059

ECMDB ID

ECMDB00606

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Not Available

Showing metabocard for 2-Hydroxyglutarate (LMDB00702)

Structure for LMDB00702 (2-Hydroxyglutarate)