Description
L-α-Hydroxyglutaric acid (L-2-HG) is an α-hydroxy acid. It is metabolized to 2-oxoglutarate (α-ketoglutarate) by L-2-hydroxyglutarate dehydrogenase, and mutations in this enzyme lead to 2-hydroxyglutaric aciduria, a neurometabolic disorder characterized by increased L-2-HG levels. L-2-HG is structurally similar to α-ketoglutarate and competitively inhibits α-ketoglutarate-dependent dioxygenases, including several involved in histone lysine and DNA demethylation.
Chemical Properties
White Solid
Uses
A potential inhibitor of glutamate carboxypeptidase.
General Description
Glutamic acid is metabolized to α-Hydroxyglutaric acid in an NAD-dependent manner by cell-free extracts of Peptococcus aerogenes. It is formed as an intermediate during glyoxylic acid metabolism in bacteria.
Biochem/physiol Actions
L-alpha-Hydroxyglutaric acid accumulates as a result of a rare defect in L-2-HG dehydogenase, leading to the metabolic disorder L-2-hydroxyglutaric aciduria (L-2HGA). L-2HGA is associated with neuronal defects, leukodystrophy and linked to an increased risk of brain tumors.
in vitro
it has been reported that l-α-hydroxyglutaric acid disodium salt could be used as the collection buffer for increasing the recovery of hypoxia-inducible factor-1 α, which was a marker of hypoxia in human tumors [1]. in another previous study, l-α-hydroxyglutaric acid disodium salt was also used in the radiolabeled conversion assay to evaluate its effect on the tet family of methyl hydroxylases [2].
in vivo
in the 30-day-old rats, l-α-hydroxyglutaric acid was found to be able to significantly increase chemiluminescence, pcf and tba-rs measurements and decrease the tar values in cerebellum markedly. in addition, the l-α-hydroxyglutaric acid-induced increase of tba-rs was significantly attenuated by melatonin and also by the combinations of ascorbic acid and soluble alpha-tocopherol (trolox) and of superoxide dismutase plus catalase but not by the inhibitor of nitric oxide synthase nomega-nitro-l-arginine methyl ester (l-name), , superoxide dismutase or creatine or catalase alone in either cerebral structure [3].
References
[1] park sr,kinders rj,khin s,et al. validation of a hypoxia-inducible factor-1 alpha specimen collection procedure and quantitative enzyme-linked immunosorbent assay in solid tumor tissues. anal biochem.2014 aug 15;459:1-11.
[2] evans b,griner e. registered report: oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. elife.2015 jul 31;4:e07420.
[3] latini a,scussiato k,rosa rb,leipnitz g,llesuy s,belló-klein a,dutra-filho cs,wajner m. induction of oxidative stress by l-2-hydroxyglutaric acid in rat brain. j neurosci res.2003 oct 1;74(1):103-10.
