D-2-hydroxyglutarate dehydrogenase
In enzymology, a D-2-hydroxyglutarate dehydrogenase (EC 1.1.99.39) is an enzyme that catalyzes the chemical reaction
- (R)-2-hydroxyglutarate + acceptor 2-oxoglutarate + reduced acceptor
| D-2-hydroxyglutarate dehydrogenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.1.99.39 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Thus, the two substrates of this enzyme are (R)-2-hydroxyglutarate and acceptor, whereas its two products are 2-oxoglutarate and reduced acceptor.
The enzyme activity has been confirmed in animals[1] as well as in plants .[2]
Nomenclature
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 (R)-2-hydroxyglutarate:acceptor 2-oxidoreductase. Other names in common use include:
- (R)-2-hydroxyglutarate:(acceptor) 2-oxidoreductase
- alpha-hydroxyglutarate dehydrogenase
- alpha-hydroxyglutarate dehydrogenase (NAD+ specific)
- alpha-hydroxyglutarate oxidoreductase
- alpha-ketoglutarate reductase
- hydroxyglutaric dehydrogenase
- D-alpha-hydroxyglutarate dehydrogenase
- D-alpha-hydroxyglutarate:NAD+ 2-oxidoreductase
Clinical significance
Deficiency in this enzyme in humans (D2HGDH) or in the model plant Arabidopsis thaliana (At4g36400) leads to massive accumulation of D-2-hydroxyglutarate. In humans this results in the fatal neurometabolic disorder 2-Hydroxyglutaric aciduria whereas plants seem to be to a large extent unaffected by high cellular concentrations of this compound.[3][4]
See also
References
- Achouri Y, Noël G, Vertommen D, Rider MH, Veiga-Da-Cunha M, Van Schaftingen E (July 2004). "Identification of a dehydrogenase acting on D-2-hydroxyglutarate". Biochem. J. 381 (Pt 1): 35–42. doi:10.1042/BJ20031933. PMC 1133759. PMID 15070399.
- Engqvist M, Drincovich MF, Flügge UI, Maurino VG (September 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". J. Biol. Chem. 284 (37): 25026–37. doi:10.1074/jbc.M109.021253. PMC 2757207. PMID 19586914.
- Araújo WL, Ishizaki K, Nunes-Nesi A, Larson TR, Tohge T, Krahnert I, Witt S, Obata T, Schauer N, Graham IA, Leaver CJ, Fernie AR (May 2010). "Identification of the 2-hydroxyglutarate and isovaleryl-CoA dehydrogenases as alternative electron donors linking lysine catabolism to the electron transport chain of Arabidopsis mitochondria". Plant Cell. 22 (5): 1549–63. doi:10.1105/tpc.110.075630. PMC 2899879. PMID 20501910.
- Engqvist MK, Kuhn A, Wienstroer J, Weber K, Jansen EE, Jakobs C, Weber AP, Maurino VG (April 2011). "Plant D-2-hydroxyglutarate dehydrogenase participates in the catabolism of lysine especially during senescence". J Biol Chem. 286 (April 1): 11382–11390. doi:10.1074/jbc.M110.194175. PMC 3064194. PMID 21296880.
Further reading
- Maurino, Veronica; Engqvist, Martin (2015). "2-Hydroxy Acids in Plant Metabolism". The Arabidopsis Book. 13: e0182. doi:10.1199/tab.0182. PMC 4568905. PMID 26380567.