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Structure Database (LMSD)

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Common Name

2-hydroxyglutaric acid

Systematic Name

2-oxidanylpentanedioic acid

Synonyms

2-hydroxyglutaric acid

LM ID

LMFA01050483

Formula

C₅H₈O₅

Exact Mass

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148.037175

Sum Composition

FA 5:1;O3

Status

Curated

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Classification

Biological Context

α-Hydroxyglutaric acid (2-HG) is an α-hydroxy acid. It is metabolized to 2-oxoglutarate by D- and L-2-hydroxyglutarate dehydrogenases, and mutations in these enzymes lead to 2-hydroxyglutaric aciduria, a neurometabolic disorder characterized by increased levels of L-2-hydroxyglutaric acid .^1,2,3 2-HG can also be metabolized from isocitrate by mutated forms of isocitrate dehydrogenase 1 (IDH1) and IDH2.4,5 2-HG is structurally similar to α-ketoglutarate, the product of wild-type isocitrate dehydrogenases, and competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone lysine demethylases and DNA hydroxylases.^5,6,7

This information has been provided by Cayman Chemical

References

1. Chowdhury, R., Yeoh, K.K., Tian, Y.M., et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 12(5), 463-469 (2011).

2. Rzem, R., Veiga-da-Cunha, M., Noël, G., et al. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc. Natl. Acad. Sci. USA 101(48), 16849-16854 (2004).

3. Struys, E.A., Verhoeven, N.M., Roos, B., et al. Disease-related metabolites in culture medium of fibroblasts from patients with D-2-hydroxyglutaric aciduria, L-2-hydroxyglutaric aciduria, and combined D/L-2-hydroxyglutaric aciduria. Clin. Chem. 49(7), 1133-1138 (2003).

4. Struys, E.A., Salomons, G.S., Achouri, Y., et al. Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am. J. Hum. Genet. 76(2), 358-360 (2005).

5. Ward, P., Patel, J., Wise, D.R., et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3), 225-234 (2010).

6. Xu, W., Yang, H., Liu, Y., et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19(1), 17-30 (2011).

7. Yang, H., Ye, D., Guan, K.L., et al. IDH1 and IDH2 mutations in tumorigenesis: Mechanistic insights and clinical perspectives. Clin. Cancer Res. 18(20), 5562-5571 (2012).