MiMeDB: Showing metabocard for D-2-Hydroxyglutaric acid (MMDBc0047975)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2021-12-11 00:18:30 UTC

Update Date

2024-04-30 20:34:36 UTC

Metabolite ID

MMDBc0047975

Metabolite Identification

Common Name

D-2-Hydroxyglutaric acid

Description

In humans, D-2-hydroxyglutaric acid is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria it is formed by a 2-hydroxyglutarate synthase. D-2-Hydroxyglutaric acid 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 alpha-ketoglutaric acid through the action of a 2-hydroxyglutarate dehydrogenase (EC 1.1.99.2). In humans, there are two such enzymes (D2HGDH and L2HGDH). Both the D and the L stereoisomers of hydroxyglutaric acid are found in body fluids. D-2-Hydroxyglutaric acid is a biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria (OMIM: 600721 ) and the genetic disorder glutaric aciduria II. 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-hydroxyglutaric acid has been reported in patients with spondyloenchondrodysplasia (OMIM: 271550 ). D-2-Hydroxyglutaric acid can be converted to alpha-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 alpha-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. D-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 D-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 D-2-hydroxyglutaric acid causes a cascading effect that leads genetic perturbations and malignant transformation. Depending on the circumstances, D-2-hydroxyglutaric acid can act 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 nerual 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, D-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, D-2-hydroxyglutaric acid mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. D-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, D-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 D-2-hydroxyglutaric acid are a feature of the inborn error of metabolism called D-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 also the characteristic symptoms of untreated D-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

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

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

Molecular Formula

C₅H₈O₅

Average Mass

148.114

Monoisotopic Mass

148.037173366

IUPAC Name

(2R)-2-hydroxypentanedioic acid

Traditional Name

D-2-hydroxyglutaric acid

CAS Registry Number

Not Available

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 )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

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	Yes	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	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0zgl-9300000000-805667744aba36281cec	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-00gv-8191000000-f6fdffd87ffe1acf65b4	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_3_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001j-1900000000-dbf80fc2b86ec60d623e	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0m5r-9600000000-d1bc7ce2206164b5bc2c	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-df3e77cb42d6f7647a64	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-1900000000-095c1140772d4cdd149b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zfr-7900000000-ce158ac5b56eff867735	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9000000000-e30760384709aa978986	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0fbi-3900000000-f88fcf3ac0dd06636b16	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0k9i-9400000000-31bf8d3bb7203e7bf200	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4u-9000000000-c0ac45c4d66178ac20cf	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0w39-4900000000-1385b471f7cdf14ca14d	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052r-9500000000-17ece6956644d4cf2069	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4r-9000000000-dbb4195080bddb5f6210	2021-09-22	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-16	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-16	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Mitochondria

Biospecimen Locations

Blood
Brain
Cerebrospinal Fluid (CSF)
Feces
Placenta
Saliva
Urine

Tissue Locations

Brain
Placenta

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192540	D-3-phosphoglycerate dehydrogenase	Unknown	O43175	Homo sapiens
MMDBp0191674	D-2-hydroxyglutarate dehydrogenase, mitochondrial	Enzyme	Q8N465	Saccharomyces cerevisiae
MMDBp0193939	Hydroxyacid-oxoacid transhydrogenase, mitochondrial	Unknown	Q8IWW8	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference
MMDBr0016467	D-2-Hydroxyglutaric acid	alpha-Ketoglutarate	(R)-2-hydroxyglutarate dehydrogenase	Dehydrogenation	RHEA	34755880
MMDBr0016555	D-2-Hydroxyglutaric acid	D-Lactic acid	D-2-hydroxyglutarate--pyruvate transhydrogenase DLD2	Hydrogenation	RHEA	34755880
MMDBr0019674	Oxoglutaric acid	NAD	D-2-hydroxyglutarate dehydrogenase, mitochondrial	Dehydrogenation	PathBank	31602464
MMDBr0024988	D-2-Hydroxyglutaric acid	alpha-Ketoglutarate	D-2-hydroxyglutarate dehydrogenase	Dehydrogenation	RHEA	34755880
MMDBr0024989	D-2-Hydroxyglutaric acid	alpha-Ketoglutarate	D-2-hydroxyglutarate dehydrogenase	Dehydrogenation	RHEA	34755880
MMDBr0038884	(R)-2-hydroxyglutaryl-CoA	D-2-Hydroxyglutaric acid	Thioesterase TesA	Hydrolysis	RHEA	34755880

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
D-2-hydroxyglutaric aciduria	Increased	Association	Human Cerebrospinal Fluid (CSF)	HMDB	8981317
D-2-hydroxyglutaric aciduria	Increased	Association	Human Blood	HMDB	8981317
D-2-hydroxyglutaric aciduria	Increased	Association	Human Urine	HMDB	6774165
D-2-hydroxyglutaric aciduria	Increased	Association	Human Urine	HMDB	8981317
D-2-hydroxyglutaric aciduria	Increased	Association	Human Blood	HMDB	8134166
D-2-hydroxyglutaric aciduria		Association	Human Cerebrospinal Fluid (CSF)	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
D-2-hydroxyglutaric aciduria		Association	Human Urine	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites
Bacteria	Firmicutes	2	Pig ; Human feces
Eukaryota/Fungi	Ascomycota	4
Bacteria	Proteobacteria	5	Human ; Human feces
Bacteria	Actinobacteria	4	Cattle ; Human
Bacteria	nah	1
Eukaryota/Fungi	Basidiomycota	8	Human feces

Exposure Sources

Source Type	Source Sub-type	Species	Data Source	Reference
Animal	Milk	Bos taurus	FooDB	31437929
Animal	Milk	Bos taurus	FooDB	31437929

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Urine	Detected and Quantified	360				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	915.997				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	1511.395				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	<15.267				umol/mmol creatinine	Children (1 - 13 years old)	Male	Normal	HMDB	6774165
Human Urine	Detected and Quantified	0.34	0.16			umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	HMDB	7586571
Human Blood	Detected and Quantified	0.7		0.3	0.9	uM	Infant (0-1 year old)	Female	Normal	HMDB	7609436
Human Blood	Detected and Quantified	68		26	123	uM	Infant (0-1 year old)	Female	D-2-Hydroxyglutaric aciduria I	HMDB	7609436
Human Blood	Detected and Quantified	366		99	757	uM	Infant (0-1 year old)	Female	D-2-Hydroxyglutaric aciduria II	HMDB	7609436
Human Blood	Detected and Quantified	68		26	123	uM	Infant (0-1 year old)	Female	D-2-hydroxyglutaric aciduria type I	HMDB	7609436
Human Urine	Detected and Quantified	2486		448	11305	umol/mmol creatinine	Infant (0-1 year old)	Female	D-2-hydroxyglutaric aciduria type II	HMDB	7609436
Human Urine	Detected and Quantified	632				umol/mmol creatinine	Infant (0-1 year old)	Female	D,L-2-hydroxyglutaric aciduria type I	HMDB	7609436
Human Urine	Detected and Quantified	6		2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Female	Normal	HMDB	7609436
Human Urine	Detected and Quantified	51.9		13.7	97.3	umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	41.5		14.6	150.3	umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	12.4		5.1	24.9	umol/mmol creatinine	Children (1-13 years old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	11.2		4.6	33.6	umol/mmol creatinine	Adolescent (13-18 years old)	Both	Normal	HMDB	8087979
Human Blood	Detected and Quantified	0.7	0.2			uM	Adult (>18 years old)	Both	Normal	HMDB	8134166
Human Blood	Detected and Quantified	61	14			uM	Adult (>18 years old)	Both	D-2-Hydroxyglutaric aciduria	HMDB	8134166
Human Blood	Detected and Quantified	217				uM	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Blood	Detected and Quantified			0.28	0.93	uM	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Cerebrospinal fluid (csf)	Detected and Quantified	61				uM	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Cerebrospinal fluid (csf)	Detected and Quantified			0.067	0.34	uM	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Urine	Detected and Quantified	4067				umol/mmol creatinine	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Urine	Detected and Quantified			2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Urine	Detected but not Quantified						Children (1-13 years old)	Female	Spondyloenchondrodysplasia	HMDB	10883451
Human Urine	Detected and Quantified	228				umol/mmol creatinine	Children (1-13 years old)	Male	D, L-2-hydroxygluraric aciduria	HMDB	10963100
Human Feces	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	20669995
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Blood	Detected and Quantified			0.3	0.9	uM	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Blood	Detected and Quantified	2.6		2.2	3.2	uM	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Cerebrospinal fluid (csf)	Detected and Quantified			0.07	0.3	uM	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Cerebrospinal fluid (csf)	Detected and Quantified	1.1		0.42	2.5	uM	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Urine	Detected and Quantified			2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Urine	Detected and Quantified	496		228	750	umol/mmol creatinine	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Urine	Detected and Quantified	427				umol/mmol creatinine	Infant (0-1 year old)	Female	D2-/L2-hydroxyglutaric aciduria	HMDB	24687295
Human Urine	Detected and Quantified	97				umol/mmol creatinine	Infant (0-1 year old)	Female	D2-/L2-hydroxyglutaric aciduria	HMDB	24687295
Human Urine	Detected and Quantified			1.5	2.1	umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	27012787
Human Urine	Detected and Quantified			1	1.8	umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	27012787
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.2		0.1	0.3	uM	Adult (>18 years old)	Both	D-2-hydroxyglutaric aciduria	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
Human Urine	Detected and Quantified	10		3	17	umol/mmol creatinine	Adult (>18 years old)	Both	D-2-hydroxyglutaric aciduria	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
Human Cerebrospinal fluid (csf)	Detected and Quantified	61				uM	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Blood	Detected and Quantified	217				uM	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Urine	Detected and Quantified	360				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	915.997				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	1511.395				umol/mmol creatinine	Children (1 - 13 years old)	Male	D-2-Hydroxyglutaric aciduria	HMDB	6774165
Human Urine	Detected and Quantified	4067				umol/mmol creatinine	Infant (0-1 year old)	Male	D-2-hydroxyglutaric aciduria	HMDB	8981317
Human Blood	Detected and Quantified	61.0	14.0			uM	Adult (>18 years old)	Both	D-2-Hydroxyglutaric aciduria	HMDB	8134166
Human Urine	Detected and Quantified	228				umol/mmol creatinine	Children (1-13 years old)	Male	D, L-2-hydroxygluraric aciduria	HMDB	10963100
Human Cerebrospinal fluid (csf)	Detected and Quantified	1.1		0.42	2.5	uM	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Blood	Detected and Quantified	2.6		2.2	3.2	uM	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Urine	Detected and Quantified	496		228	750	umol/mmol creatinine	Infant (0-1 year old)	Both	Combined D,L-2-hydroxyglutaric aciduria	HMDB	22391998
Human Urine	Detected and Quantified	<15.267				umol/mmol creatinine	Children (1 - 13 years old)	Male	Normal	HMDB	6774165
Human Cerebrospinal fluid (csf)	Detected and Quantified			0.0670	0.340	uM	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Cerebrospinal fluid (csf)	Detected and Quantified			0.07	0.3	uM	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Blood	Detected and Quantified			0.280	0.930	uM	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Blood	Detected and Quantified			0.3	0.9	uM	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Urine	Detected and Quantified	0.34	0.16			umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	HMDB	7586571
Human Blood	Detected and Quantified	0.7	0.2			uM	Adult (>18 years old)	Both	Normal	HMDB	8134166
Human Blood	Detected and Quantified	0.7		0.3	0.9	uM	Infant (0-1 year old)	Female	Normal	HMDB	7609436
Human Urine	Detected and Quantified			1.0	1.8	umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	27012787
Human Urine	Detected and Quantified			1.5	2.1	umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	27012787
Human Urine	Detected and Quantified	11.2		4.6	33.6	umol/mmol creatinine	Adolescent (13-18 years old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	12.4		5.1	24.9	umol/mmol creatinine	Children (1-13 years old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified			2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Male	Normal	HMDB	8981317
Human Urine	Detected and Quantified			2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	22391998
Human Urine	Detected and Quantified	41.5		14.6	150.3	umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	51.9		13.7	97.3	umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	8087979
Human Urine	Detected and Quantified	6		2.8	17	umol/mmol creatinine	Infant (0-1 year old)	Female	Normal	HMDB	7609436
Human Cerebrospinal fluid (csf)	Detected and Quantified	0.2		0.1	0.30	uM	Adult (>18 years old)	Both	D-2-hydroxyglutaric aciduria	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
Human Urine	Detected and Quantified	10.0		3.0	17.0	umol/mmol creatinine	Adult (>18 years old)	Both	D-2-hydroxyglutaric aciduria	HMDB	MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)
Human Urine	Detected and Quantified	<26.15				umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	HMDB	BC Children's Hospital Biochemical Genetics Lab
Human Brain	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Placenta	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Feces	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	20669995

External Links

HMDB ID

HMDB0000606

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB022139

KNApSAcK ID

Not Available

Chemspider ID

388508

KEGG Compound ID

C01087

BioCyc ID

R-2-HYDROXYGLUTARATE

BiGG ID

Not Available

Wikipedia Link

Alpha-Hydroxyglutaric acid

METLIN ID

5581

PubChem Compound

439391

PDB ID

Not Available

ChEBI ID

32796

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

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. doi: 10.1203/00006450-199309000-00007. [PubMed:8134166 ]
van der Knaap MS, Jakobs C, Hoffmann GF, Nyhan WL, Renier WO, Smeitink JA, Catsman-Berrevoets CE, Hjalmarson O, Vallance H, Sugita K, Bowe CM, Herrin JT, Craigen WJ, Buist NR, Brookfield DS, Chalmers RA: D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? Ann Neurol. 1999 Jan;45(1):111-9. doi: 10.1002/1531-8249(199901)45:1<111::aid-art17>3.0.co;2-n. [PubMed:9894884 ]
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. doi: 10.1002/1099-0801(200008)14:5<317::AID-BMC989>3.0.CO;2-V. [PubMed:10960831 ]
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. doi: 10.1046/j.1460-9568.2002.02055.x. [PubMed:12153528 ]
Clarke NF, Andrews I, Carpenter K, Jakobs C, van der Knaap MS, Kirk EP: D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. Am J Med Genet A. 2003 Aug 1;120A(4):523-7. doi: 10.1002/ajmg.a.20120. [PubMed:12884432 ]
da Silva CG, Bueno AR, Schuck PF, Leipnitz G, Ribeiro CA, Wannmacher CM, Wyse AT, Wajner M: D-2-hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats. Eur J Clin Invest. 2003 Oct;33(10):840-7. doi: 10.1046/j.1365-2362.2003.01237.x. [PubMed:14511354 ]
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 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Showing metabocard for D-2-Hydroxyglutaric acid (MMDBc0047975)

MOL for #<Metabolite:0x00007fe2a3e261d8>

3D MOL for #<Metabolite:0x00007fe2a3e261d8>

3D SDF for #<Metabolite:0x00007fe2a3e261d8>

3D-SDF for #<Metabolite:0x00007fe2a3e261d8>

PDB for #<Metabolite:0x00007fe2a3e261d8>

3D PDB for #<Metabolite:0x00007fe2a3e261d8>

SMILES for #<Metabolite:0x00007fe2a3e261d8>

INCHI for #<Metabolite:0x00007fe2a3e261d8>

Structure for #<Metabolite:0x00007fe2a3e261d8>

3D Structure for #<Metabolite:0x00007fe2a3e261d8>