| Record Information |
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| Version | 5.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2005-11-16 15:48:42 UTC |
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| Update Date | 2023-02-21 17:14:59 UTC |
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| HMDB ID | HMDB0000606 |
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| Secondary Accession Numbers | - HMDB0002323
- HMDB00606
- HMDB02323
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| Metabolite Identification |
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| Common Name | D-2-Hydroxyglutaric acid |
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| 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. | Read more...
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| Structure | 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 |
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| Synonyms | | Value | Source |
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| (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 |
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| Chemical Formula | C5H8O5 |
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| Average Molecular Weight | 148.114 |
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| Monoisotopic Molecular Weight | 148.037173366 |
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| IUPAC Name | (2R)-2-hydroxypentanedioic acid |
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| Traditional Name | D-2-hydroxyglutaric acid |
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| CAS Registry Number | 13095-47-1 |
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| SMILES | O[C@H](CCC(O)=O)C(O)=O |
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| 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 |
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| InChI Key | HWXBTNAVRSUOJR-GSVOUGTGSA-N |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Organic acids and derivatives |
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| Class | Hydroxy acids and derivatives |
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| Sub Class | Short-chain hydroxy acids and derivatives |
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| Direct Parent | Short-chain hydroxy acids and derivatives |
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| Alternative Parents | |
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| 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
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | |
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| Ontology |
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| Physiological effect | |
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| Disposition | |
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| Physical Properties |
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| State | Solid |
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| Experimental Molecular Properties | | Property | Value | Reference |
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| Melting Point | > 300 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Experimental Chromatographic Properties | Not Available |
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| Predicted Molecular Properties | | Show more...
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| Predicted Chromatographic Properties | Predicted Collision Cross SectionsPredicted Kovats Retention IndicesUnderivatizedDerivatized| Derivative Name / Structure | SMILES | Kovats RI Value | Column Type | Reference |
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| D-2-Hydroxyglutaric acid,1TMS,isomer #1 | C[Si](C)(C)O[C@H](CCC(=O)O)C(=O)O | 1441.3 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,1TMS,isomer #2 | C[Si](C)(C)OC(=O)CC[C@@H](O)C(=O)O | 1442.3 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,1TMS,isomer #3 | C[Si](C)(C)OC(=O)[C@H](O)CCC(=O)O | 1400.3 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TMS,isomer #1 | C[Si](C)(C)OC(=O)CC[C@@H](O[Si](C)(C)C)C(=O)O | 1536.2 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TMS,isomer #2 | C[Si](C)(C)OC(=O)[C@@H](CCC(=O)O)O[Si](C)(C)C | 1504.0 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TMS,isomer #3 | C[Si](C)(C)OC(=O)CC[C@@H](O)C(=O)O[Si](C)(C)C | 1476.7 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,3TMS,isomer #1 | C[Si](C)(C)OC(=O)CC[C@@H](O[Si](C)(C)C)C(=O)O[Si](C)(C)C | 1584.8 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,1TBDMS,isomer #1 | CC(C)(C)[Si](C)(C)O[C@H](CCC(=O)O)C(=O)O | 1698.7 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,1TBDMS,isomer #2 | CC(C)(C)[Si](C)(C)OC(=O)CC[C@@H](O)C(=O)O | 1702.2 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,1TBDMS,isomer #3 | CC(C)(C)[Si](C)(C)OC(=O)[C@H](O)CCC(=O)O | 1672.0 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TBDMS,isomer #1 | CC(C)(C)[Si](C)(C)OC(=O)CC[C@@H](O[Si](C)(C)C(C)(C)C)C(=O)O | 1992.1 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TBDMS,isomer #2 | CC(C)(C)[Si](C)(C)OC(=O)[C@@H](CCC(=O)O)O[Si](C)(C)C(C)(C)C | 1979.7 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,2TBDMS,isomer #3 | CC(C)(C)[Si](C)(C)OC(=O)CC[C@@H](O)C(=O)O[Si](C)(C)C(C)(C)C | 1935.0 | Semi standard non polar | 33892256 | | D-2-Hydroxyglutaric acid,3TBDMS,isomer #1 | CC(C)(C)[Si](C)(C)OC(=O)CC[C@@H](O[Si](C)(C)C(C)(C)C)C(=O)O[Si](C)(C)C(C)(C)C | 2222.5 | Semi standard non polar | 33892256 |
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| Spectra |
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| GC-MS Spectra| Spectrum Type | Description | Splash Key | Deposition Date | Source | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (Non-derivatized) - 70eV, Positive | splash10-0zgl-9300000000-805667744aba36281cec | 2017-09-01 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (3 TMS) - 70eV, Positive | splash10-00gv-8191000000-f6fdffd87ffe1acf65b4 | 2017-10-06 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_1_1) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_1_2) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_1_3) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_2_1) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_2_2) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TMS_2_3) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_1_2) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_1_3) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_2_1) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_2_2) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_2_3) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - D-2-Hydroxyglutaric acid GC-MS (TBDMS_3_1) - 70eV, Positive | Not Available | 2021-11-05 | Wishart Lab | View Spectrum |
MS/MS Spectra| Spectrum Type | Description | Splash Key | Deposition Date | Source | View |
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| Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 10V, Positive-QTOF | splash10-001j-1900000000-dbf80fc2b86ec60d623e | 2016-06-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 20V, Positive-QTOF | splash10-0m5r-9600000000-d1bc7ce2206164b5bc2c | 2016-06-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 40V, Positive-QTOF | splash10-0a4i-9000000000-df3e77cb42d6f7647a64 | 2016-06-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 10V, Negative-QTOF | splash10-0002-1900000000-095c1140772d4cdd149b | 2016-08-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 20V, Negative-QTOF | splash10-0zfr-7900000000-ce158ac5b56eff867735 | 2016-08-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 40V, Negative-QTOF | splash10-0a4i-9000000000-e30760384709aa978986 | 2016-08-03 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 10V, Negative-QTOF | splash10-0fbi-3900000000-f88fcf3ac0dd06636b16 | 2021-09-22 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 20V, Negative-QTOF | splash10-0k9i-9400000000-31bf8d3bb7203e7bf200 | 2021-09-22 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 40V, Negative-QTOF | splash10-0a4u-9000000000-c0ac45c4d66178ac20cf | 2021-09-22 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 10V, Positive-QTOF | splash10-0w39-4900000000-1385b471f7cdf14ca14d | 2021-09-22 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 20V, Positive-QTOF | splash10-052r-9500000000-17ece6956644d4cf2069 | 2021-09-22 | Wishart Lab | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - D-2-Hydroxyglutaric acid 40V, Positive-QTOF | splash10-0a4r-9000000000-dbb4195080bddb5f6210 | 2021-09-22 | Wishart Lab | View Spectrum |
NMR Spectra| Spectrum Type | Description | Deposition Date | Source | View |
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| Predicted 1D NMR | 13C NMR Spectrum (1D, 100 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 100 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 200 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 200 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 300 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 300 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 400 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 400 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 500 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 500 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 600 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 600 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 700 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 700 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 800 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 800 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 900 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 900 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 13C NMR Spectrum (1D, 1000 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum | | Predicted 1D NMR | 1H NMR Spectrum (1D, 1000 MHz, D2O, predicted) | 2021-09-16 | Wishart Lab | View Spectrum |
IR Spectra| Spectrum Type | Description | Deposition Date | Source | View |
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| Predicted IR Spectrum | IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M-H]-) | 2023-02-03 | FELIX lab | View Spectrum | | Predicted IR Spectrum | IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+H]+) | 2023-02-03 | FELIX lab | View Spectrum | | Predicted IR Spectrum | IR Ion Spectrum (Predicted IRIS Spectrum, Adduct: [M+Na]+) | 2023-02-03 | FELIX lab | View Spectrum |
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| Biological Properties |
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| Cellular Locations | - Cytoplasm (predicted from logP)
- Mitochondria
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| Biospecimen Locations | - Blood
- Cerebrospinal Fluid (CSF)
- Feces
- Saliva
- Urine
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| Tissue Locations | |
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| Pathways | |
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| Normal Concentrations |
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| Blood | Detected and Quantified | 0.280-0.930 uM | Infant (0-1 year old) | Male | Normal | | details | | Blood | Detected and Quantified | 0.3-0.9 uM | Infant (0-1 year old) | Both | Normal | | details | | Blood | Detected and Quantified | 0.7(0.3-0.9) uM | Infant (0-1 year old) | Female | Normal | | details | | Blood | Detected and Quantified | 0.7 +/- 0.2 uM | Adult (>18 years old) | Both | Normal | | details | | Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.07-0.3 uM | Infant (0-1 year old) | Both | Normal | | details | | Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.0670-0.340 uM | Infant (0-1 year old) | Male | Normal | | details | | Feces | Detected but not Quantified | Not Quantified | Not Specified | Not Specified | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Saliva | Detected but not Quantified | Not Quantified | Adult (>18 years old) | Male | Normal | | details | | Urine | Detected and Quantified | 11.2 (4.6-33.6) umol/mmol creatinine | Adolescent (13-18 years old) | Both | Normal | | details | | Urine | Detected and Quantified | 2.8-17 umol/mmol creatinine | Infant (0-1 year old) | Male | Normal | | details | | Urine | Detected and Quantified | 1.5-2.1 umol/mmol creatinine | Adult (>18 years old) | Female | Normal | | details | | Urine | Detected and Quantified | <15.267 umol/mmol creatinine | Children (1 - 13 years old) | Male | Normal | | details | | Urine | Detected and Quantified | 0.34 +/- 0.16 umol/mmol creatinine | Children (1-13 years old) | Not Specified | Normal | | details | | Urine | Detected and Quantified | 2.8-17 umol/mmol creatinine | Infant (0-1 year old) | Both | Normal | | details | | Urine | Detected and Quantified | 6(2.8-17) umol/mmol creatinine | Infant (0-1 year old) | Female | Normal | | details | | Urine | Detected and Quantified | <26.15 umol/mmol creatinine | Children (1 - 18 years old) | Both | Normal | | details | | Urine | Detected and Quantified | 1.0-1.8 umol/mmol creatinine | Adult (>18 years old) | Male | Normal | | details | | Urine | Detected and Quantified | 51.9 (13.7-97.3) umol/mmol creatinine | Newborn (0-30 days old) | Both | Normal | | details | | Urine | Detected and Quantified | 41.5 (14.6-150.3) umol/mmol creatinine | Infant (0-1 year old) | Both | Normal | | details | | Urine | Detected and Quantified | 12.4 (5.1-24.9) umol/mmol creatinine | Children (1-13 years old) | Both | Normal | | details |
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| Abnormal Concentrations |
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| Blood | Detected and Quantified | 217 uM | Infant (0-1 year old) | Male | D-2-hydroxyglutaric aciduria | | details | | Blood | Detected and Quantified | 2.6(2.2-3.2) uM | Infant (0-1 year old) | Both | Combined D,L-2-hydroxyglutaric aciduria | | details | | Blood | Detected and Quantified | 366(99-757) uM | Infant (0-1 year old) | Female | D-2-Hydroxyglutaric aciduria II | | details | | Blood | Detected and Quantified | 68(26-123) uM | Infant (0-1 year old) | Female | D-2-Hydroxyglutaric aciduria I | | details | | Blood | Detected and Quantified | 68(26-123) uM | Infant (0-1 year old) | Female | D-2-hydroxyglutaric aciduria type I | | details | | Blood | Detected and Quantified | 61.0 +/- 14.0 uM | Adult (>18 years old) | Both | D-2-Hydroxyglutaric aciduria | | details | | 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 | | details | | Cerebrospinal Fluid (CSF) | Detected and Quantified | 61 uM | Infant (0-1 year old) | Male | D-2-hydroxyglutaric aciduria | | details | | Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.2 (0.1-0.30) uM | Adult (>18 years old) | Both | D-2-hydroxyglutaric aciduria | | details | | Urine | Detected but not Quantified | Not Quantified | Children (1-13 years old) | Female | Spondyloenchondrodysplasia | | details | | Urine | Detected and Quantified | 228 umol/mmol creatinine | Children (1-13 years old) | Male | D, L-2-hydroxygluraric aciduria | | details | | Urine | Detected and Quantified | 4067 umol/mmol creatinine | Infant (0-1 year old) | Male | D-2-hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 97 umol/mmol creatinine | Infant (0-1 year old) | Female | D2-/L2-hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 360 umol/mmol creatinine | Children (1 - 13 years old) | Male | D-2-Hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 427 umol/mmol creatinine | Infant (0-1 year old) | Female | D2-/L2-hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 632 umol/mmol creatinine | Infant (0-1 year old) | Female | D,L-2-hydroxyglutaric aciduria type I | | details | | Urine | Detected and Quantified | 915.997 umol/mmol creatinine | Children (1 - 13 years old) | Male | D-2-Hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 1511.395 umol/mmol creatinine | Children (1 - 13 years old) | Male | D-2-Hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 2486(448-11305) umol/mmol creatinine | Infant (0-1 year old) | Female | D-2-hydroxyglutaric aciduria type II | | details | | Urine | Detected and Quantified | 496(228-750) umol/mmol creatinine | Infant (0-1 year old) | Both | Combined D,L-2-hydroxyglutaric aciduria | | details | | Urine | Detected and Quantified | 10.0 (3.0-17.0) umol/mmol creatinine | Adult (>18 years old) | Both | D-2-hydroxyglutaric aciduria | | details |
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| Associated Disorders and Diseases |
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| Disease References | | D-2-hydroxyglutaric aciduria |
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- 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. [PubMed:8134166 ]
- Chalmers RA, Lawson AM, Watts RW, Tavill AS, Kamerling JP, Hey E, Ogilvie D: D-2-hydroxyglutaric aciduria: case report and biochemical studies. J Inherit Metab Dis. 1980;3(1):11-5. [PubMed:6774165 ]
- Geerts Y, Renier WO, Bakkeren J, de Jong J: 2-Hydroxyglutaric aciduria: a case report on an infant with the D-isomeric form with review of the literature. J Neurol Sci. 1996 Nov;143(1-2):166-9. [PubMed:8981317 ]
- G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
| | D, L-2-hydroxyglutaric aciduria |
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- Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C: Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-87. doi: 10.1007/s10545-012-9462-5. Epub 2012 Mar 6. [PubMed:22391998 ]
- Muntau AC, Roschinger W, Merkenschlager A, van der Knaap MS, Jakobs C, Duran M, Hoffmann GF, Roscher AA: Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria? Neuropediatrics. 2000 Jun;31(3):137-40. doi: 10.1055/s-2000-7497. [PubMed:10963100 ]
- G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
| | Spondyloenchondrodysplasia |
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- Talkhani IS, Saklatvala J, Dwyer J: D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. Skeletal Radiol. 2000 May;29(5):289-92. [PubMed:10883451 ]
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| Associated OMIM IDs | - 600721 (D-2-hydroxyglutaric aciduria)
- 615182 (D, L-2-hydroxyglutaric aciduria)
- 271550 (Spondyloenchondrodysplasia)
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| External Links |
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| DrugBank ID | Not Available |
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| Phenol Explorer Compound ID | Not Available |
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| FooDB ID | FDB022139 |
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| KNApSAcK ID | Not Available |
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| Chemspider ID | 388508 |
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| KEGG Compound ID | C01087 |
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| BioCyc ID | R-2-HYDROXYGLUTARATE |
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| BiGG ID | Not Available |
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| Wikipedia Link | Alpha-Hydroxyglutaric acid |
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| METLIN ID | 5581 |
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| PubChem Compound | 439391 |
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| PDB ID | Not Available |
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| ChEBI ID | 32796 |
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| Food Biomarker Ontology | Not Available |
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| VMH ID | Not Available |
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| MarkerDB ID | MDB00000198 |
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| Good Scents ID | Not Available |
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| References |
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| Synthesis Reference | Kobayashi, Hidehiko; Yamaguchi, Koretaka; Yamashita, Takeshi. a-Hydroxyglutaric acid from glutamic acid. Jpn. Tokkyo Koho (1968), 3 pp. |
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| Material Safety Data Sheet (MSDS) | Not Available |
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| 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. [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. [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. [PubMed:10960831 ]
- 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. [PubMed:14511354 ]
- 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. [PubMed:12884432 ]
- 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 ]
- 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. [PubMed:12153528 ]
- 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 ]
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