alpha-Hydroxyglutaric acid

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α-Hydroxyglutaric acid
Alpha-hydroxyglutaric acid.png
IUPAC name
2-Hydroxypentanedioic acid
Other names
2-Hydroxyglutaric acid
3D model (JSmol)
MeSH Alpha-hydroxyglutarate
Molar mass 148.11 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an alpha hydroxy acid form of glutaric acid.

In biology[edit]

In humans the compound is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria is formed by a 2-hydroxyglutarate synthase. The compound can be converted to α-ketoglutaric acid through the action of a 2-hydroxyglutarate dehydrogenase which, in humans, are two enzymes called D2HGDH and L2HGDH. Deficiency in either of these two enzymes lead to a disease known as 2-hydroxyglutaric aciduria.


Mutations in isocitrate dehydrogenase (IDH1 and IDH2), which frequently occur in glioma and AML,[1][2][3] produce (D)-2-hydroxyglutarate from alpha-ketoglutarate. (D)-2-hydroxyglutarate accumulates to very high concentrations which inhibits the function of enzymes that are dependent on alpha-ketoglutarate. This leads to a hypermethylated state of DNA and histones,[4] which results in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes.

On the other hand, (L)-2-hydroxyglutarate is produced to high levels in low oxygen conditions, including cells of the immune system [5]


  1. ^ Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (November 2009). "Monoclonal antibody specific for IDH1 R132H mutation". Acta Neuropathol. 118 (5): 599–601. doi:10.1007/s00401-009-0595-z. PMID 19798509. 
  2. ^ Ward PS, Patel J, Wise DR, et al. (March 2010). "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate". Cancer Cell. 17 (3): 225–34. doi:10.1016/j.ccr.2010.01.020. PMC 2849316Freely accessible. PMID 20171147. 
  3. ^ Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L, Wang P, Yang H, Ma S, Lin H, Jiao B, Ren R, Ye D, Guan KL, Xiong Y (Feb 2015). "WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation". Molecular Cell. 57 (4): 662–73. doi:10.1016/j.molcel.2014.12.023. PMC 4336627Freely accessible. PMID 25601757. 
  4. ^ Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y (Jan 2011). "Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases". Cancer Cell. 19 (1): 17–30. doi:10.1016/j.ccr.2010.12.014. PMC 3229304Freely accessible. PMID 21251613. 
  5. ^ Tyrakis PA, Palazon A, Macias D, Lee KL, Phan AT, Veliça P, You J, Chia GS, Sim J, Doedens A, Abelanet A, Evans CE, Griffiths JR, Poellinger L, Goldrath AW, Johnson RS (Dec 2016). "S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate". Nature. 540 (7632): 236–241. doi:10.1038/nature20165. PMC 5149074Freely accessible. PMID 27798602.