α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an
alpha hydroxy acid form of
glutaric acid.
In biology
In humans the compound is formed by a
hydroxyacid-oxoacid transhydrogenase whereas in bacteria is formed by a
2-hydroxyglutarate synthase
In enzymology, a 2-hydroxyglutarate synthase () is an enzyme that catalyzes the chemical reaction
:propanoyl-CoA + H2O + glyoxylate \rightleftharpoons 2-hydroxyglutarate + CoA
The 3 substrates of this enzyme are propanoyl-CoA, H2O, and glyoxyl ...
. The compound can be converted to
α-ketoglutaric acid
α-Ketoglutaric acid (2-oxoglutaric acid) is one of two ketone derivatives of glutaric acid. The term "ketoglutaric acid," when not further qualified, almost always refers to the alpha variant. β-Ketoglutaric acid varies only by the position o ...
through the action of a
2-hydroxyglutarate dehydrogenase
2-hydroxyglutarage dehydrogenase may refer to:
* L-2-hydroxyglutarate dehydrogenase, an enzyme specific to L-2-hydroxyglutarate (EC 1.1.99.2)
* D-2-hydroxyglutarate dehydrogenase, an enzyme specific to D-2-hydroxyglutarate (EC 1.1.99.39)
{{e ...
which, in humans, are two enzymes called
D2HGDH
D-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ''D2HGDH'' gene.
This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase t ...
and
L2HGDH
L-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ''L2HGDH'' gene, also known as C14orf160, on chromosome 14.
Function
This gene encodes L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucle ...
. Deficiency in either of these two enzymes lead to a disease known as
2-hydroxyglutaric aciduria
2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine. It is either autosomal recessive or autosomal dominant.
Presentation
The signs/symptoms of thi ...
.
D-2-hydroxyglutarate
Mutations in
isocitrate dehydrogenase (
IDH1 and
IDH2), which frequently occur in
glioma and
AML,
[
] produce
D-2-hydroxyglutarate from
alpha-ketoglutarate.
-2-hydroxyglutarate accumulates to very high concentrations which inhibits the function of enzymes that are dependent on alpha-ketoglutarate, including
histone lysine demethylases.
This leads to a hypermethylated state of DNA and histones,
which results in different gene expression that can activate
oncogenes and inactivate
tumor-suppressor gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
s. Studies have also shown that 2-hydroxyglutarate may be converted back to alpha-ketoglutarate either enzymatically or non-enzymatically.
Further studies are required to fully understand the dynamics between 2-hydroxyglutarate and alpha-ketoglutarate.
L-2-hydroxyglutarate
On the other hand, L-2-hydroxyglutarate is produced at high levels in low oxygen conditions, including cells of the immune system.
[ ]
References
{{DEFAULTSORT:Hydroxyglutaric acid, alpha-
Dicarboxylic acids
Alpha hydroxy acids