4301 L-2-Hydroxyglutaric acid L-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. 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. 13095-48-2 439939 C5H8O5 White powder. Endogenous, Injection 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. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. L-2-hydroxyglutarate is structurally similar to the excitatory amino acid glutamate and stimulates neurodegeneration by mechanisms well-known for glutamate, NMDA or mitochondrial toxins (A15198). Not listed by IARC. Has been implicated in oncogenesis (A15091, A15090). Chronically high levels of L-2-hydroxyglutaric acid are associated with the inborn error of metabolism called: 2-Hydroxyglutaric Aciduria. L-2-hydroxyglutarate is neurotoxic. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. Symptoms of L-2-Hydroxyglutaric Aciduria include hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression. Chronic exposure of high levels of L-2-hydroxyglutarate leads to hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression. 2014-08-29T06:03:11Z 2026-04-06T11:40:12Z C03196 32797 S2G true [H][C@](O)(CCC(O)=O)C(O)=O C5H8O5 InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m0/s1 HWXBTNAVRSUOJR-VKHMYHEASA-N 148.114 148.037173366 Endogenous Solid HMDB00694 CHEMBL1615211 388969 Kobayashi, Hidehiko; Yamaguchi, Koretaka; Yamashita, Takeshi. a-Hydroxyglutaric acid from glutamic acid. Jpn. Tokkyo Koho (1968), 3 pp. CHEM003207 NS00122108 94.83000000000001 29.6302 12.9730498807228 4 5 3 3.276485914460605 -3.8068384384876675 -2 0 -1.04 0.03 1.57e+02 g/l