L-2-hydroxyglutarate dehydrogenase

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L-2-hydroxyglutarate dehydrogenase
EC no.
CAS no.9028-80-2
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

In enzymology, an L-2-hydroxyglutarate dehydrogenase (EC is an enzyme that catalyzes the chemical reaction

(S)-2-hydroxyglutarate + acceptor 2-oxoglutarate + reduced acceptor

Thus, the two substrates of this enzyme are (S)-2-hydroxyglutarate and acceptor, whereas its two products are 2-oxoglutarate and reduced acceptor. [1][2] Enzymes which preferentially catalyze the conversion of the (R) stereoisomer of 2-oxoglutarate also exist in both mammals and plants [3] [4] and are named D-2-hydroxyglutarate dehydrogenase. L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate; L-2-hydroxyglutarate dehydrogenase is an example of a metabolite repair enzyme that oxidizes L-2-hydroxyglutarate back to 2-oxoglutarate.


This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with other acceptors. The systematic name of this enzyme class is (S)-2-hydroxyglutarate:acceptor 2-oxidoreductase. Other names in common use include:

  • (S)-2-hydroxyglutarate:(acceptor) 2-oxidoreductase
  • alpha-hydroxyglutarate dehydrogenase
  • alpha-hydroxyglutarate dehydrogenase (NAD+ specific)
  • alpha-hydroxyglutarate oxidoreductase
  • alpha-ketoglutarate reductase
  • hydroxyglutaric dehydrogenase
  • L-alpha-hydroxyglutarate dehydrogenase
  • L-alpha-hydroxyglutarate:NAD+ 2-oxidoreductase

Clinical significance[edit]

Deficiency in this enzyme in humans (L2HGDH) or in the model plant Arabidopsis thaliana (At3g56840) leads to accumulation of L-2-hydroxyglutarate. In humans this results in the fatal neurometabolic disorder 2-Hydroxyglutaric aciduria whereas plants seem to be unaffected by elevated cellular concentrations of this compound [1] [2] [5]

See also[edit]


  1. ^ a b Rzem R, Van Schaftingen E, Veiga-da-Cunha M (Jan 2006). "The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase". Biochimie. 88 (1): 113–6. doi:10.1016/j.biochi.2005.06.005. PMID 16005139.
  2. ^ a b Hüdig M, Maier A, Scherrers I, Seidel L, Jansen EE, Mettler-Altmann T, Engqvist MK, Maurino VG (Sep 2015). "Plants Possess a Cyclic Mitochondrial Metabolic Pathway similar to the Mammalian Metabolic Repair Mechanism Involving Malate Dehydrogenase and l-2-Hydroxyglutarate Dehydrogenase". Plant & Cell Physiology. 56 (9): 1820–30. doi:10.1093/pcp/pcv108. PMID 26203119.
  3. ^ Achouri Y, Noël G, Vertommen D, Rider MH, Veiga-Da-Cunha M, Van Schaftingen E (Jul 2004). "Identification of a dehydrogenase acting on D-2-hydroxyglutarate". The Biochemical Journal. 381 (Pt 1): 35–42. doi:10.1042/BJ20031933. PMC 1133759. PMID 15070399.
  4. ^ Engqvist M, Drincovich MF, Flügge UI, Maurino VG (Sep 2009). "Two D-2-hydroxy-acid dehydrogenases in Arabidopsis thaliana with catalytic capacities to participate in the last reactions of the methylglyoxal and beta-oxidation pathways". The Journal of Biological Chemistry. 284 (37): 25026–37. doi:10.1074/jbc.M109.021253. PMC 2757207. PMID 19586914.
  5. ^ Rzem R, Veiga-da-Cunha M, Noël G, Goffette S, Nassogne MC, Tabarki B, Schöller C, Marquardt T, Vikkula M, Van Schaftingen E (Nov 2004). "A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria". Proceedings of the National Academy of Sciences of the United States of America. 101 (48): 16849–54. Bibcode:2004PNAS..10116849R. doi:10.1073/pnas.0404840101. PMC 534725. PMID 15548604.

Further reading[edit]