α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an alpha hydroxy acid form of glutaric acid.
| |
| Names | |
|---|---|
| Preferred IUPAC name
2-Hydroxypentanedioic acid | |
| Other names
2-Hydroxyglutaric acid | |
| Identifiers | |
3D model (JSmol) |
|
| 1723805 | |
| ChEBI | |
| ChemSpider |
|
| KEGG |
|
| MeSH | Alpha-hydroxyglutarate |
PubChem CID |
|
| UNII | |
CompTox Dashboard (EPA) |
|
| |
| |
| Properties | |
| C5H8O5 | |
| Molar mass | 148.114 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
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 which, in humans, are two enzymes called D2HGDH and L2HGDH. Deficiency in either of these two enzymes lead to a disease known as 2-hydroxyglutaric aciduria.
Mutations in isocitrate dehydrogenase (IDH1 and IDH2), which frequently occur in glioma and AML,[1][2][3] produce D-2-hydroxyglutarate from alpha-ketoglutarate.[4] D-2-hydroxyglutarate accumulates to very high concentrations which inhibits the function of enzymes that are dependent on alpha-ketoglutarate, including histone lysine demethylases.[5][6] This leads to a hypermethylated state of DNA and histones,[7] which results in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes. Studies have also shown that 2-hydroxyglutarate may be converted back to alpha-ketoglutarate either enzymatically or non-enzymatically.[8][9] Further studies are required to fully understand the dynamics between 2-hydroxyglutarate and alpha-ketoglutarate.
On the other hand, L-2-hydroxyglutarate is produced at high levels in low oxygen conditions, including cells of the immune system.[10]
