α-Hydroxyglutaric acid

α-Hydroxyglutaric acid (2-Hydroxyglutarate) is an α-hydroxy acid form of glutaric acid. α-Hydroxyglutaric acid is a competitive inhibitor of multiple α-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Demethylase

Isocitrate Dehydrogenase 1 (IDH1) and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and α-Hydroxyglutaric acid (2-Hydroxyglutarate), respectively[1]. α-Hydroxyglutaric acid (2-Hydroxyglutarate) inhibits the activity of multiple histone demethylases. α-Hydroxyglutaric acid occupies the same space as α-KG does in the active site of histone demethylases. α-Hydroxyglutaric acid (2-Hydroxyglutarate) inhibits the activity of TET 5-methylcytosine hydroxylases[1]. Treatment of U-87MG cells with α-Hydroxyglutaric acid (2-Hydroxyglutarate; 10-50 mM) increases HIF-1α and decreases endostatin[1].

[1]. Wei Xu, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30.