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).
|
α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an alpha hydroxy acid form of glutaric 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 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]
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).
|
α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an alpha hydroxy acid form of glutaric 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 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]