103404-90-6

D-α-Hydroxyglutaric Acid (D-2-HG) is an α-hydroxy acid that is over-produced in the human neurometabolic disease D-2-hydroxyglutaric aciduria (D-2-HGA). It is normally synthesized from 2-ketoglutarate (2-KG) by hydroxyacid-oxoacid transhydrogenase (HOT), although defects in HOT are not known to be associated with D-2-HGA. Instead, type I D-2-HGA involves mutations in D-2-hydroxyglutarate dehydrogenase, which converts D-2-HG back to 2-KG. Type II D-2-HGA results from gain-of-function mutations in isocitrate dehydrogenase 2, causing it to supplement HOT in converting 2-KG to D-2-HG. In bacteria, this α-hydroxy acid may be synthesized from oxalate and propionyl-coenzyme A by an α-hydroxyglutaric acid synthetase.

Pale Orange Solid

A potential inhibitor of glutamate carboxypeptidase.

Biomarker for inborn errors of metabolism and cancer

Store at -20°C

[1] XUDONG FU. 2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling.[J]. Cell metabolism, 2015, 22 3: 508-515. DOI: 10.1016/j.cmet.2015.06.009
[2] ALEXANDRA LATINI. D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats[J]. European Journal of Neuroscience, 2003, 17 10: 2017-2022. DOI: 10.1046/j.1460-9568.2003.02639.x
[3] MARTIJN KRANENDIJK. IDH2 Mutations in Patients with d-2-Hydroxyglutaric Aciduria[J]. Science, 2010, 330 6002. DOI: 10.1126/science.1192632
[4] EDUARD A STRUYS. Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria.[J]. American journal of human genetics, 2005, 76 2: 358-360. DOI: 10.1086/427890
[5] HUI YANG. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives.[J]. Clinical Cancer Research, 2012, 18 20: 5562-5571. DOI: 10.1158/1078-0432.ccr-12-1773
[6] WEI XU. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.[J]. Cancer Cell, 2011, 19 1: 17-30. DOI: 10.1016/j.ccr.2010.12.014
[7] RASHEDUZZAMAN CHOWDHURY. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.[J]. EMBO Reports, 2011, 12 5: 463-469. DOI: 10.1038/embor.2011.43