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Information on EC 1.1.99.39 - D-2-hydroxyglutarate dehydrogenase and Organism(s) Homo sapiens

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IUBMB Comments
Contains FAD. The enzyme has no activity with NAD+ or NADP+, and was assayed in vitro using artificial electron acceptors. It has lower activity with (R)-lactate, (R)-2-hydroxybutyrate and meso-tartrate, and no activity with the (S) isomers. The mammalian enzyme is stimulated by Zn2+, Co2+ and Mn2+.
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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
d2hgdh, d-2-hga, d-2-hydroxyglutarate dehydrogenase, d2hdh, atd-2hgdh, d-2-hg dehydrogenase, d2-hydroxyglutarate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D-2-HGA
-
-
D-2-hydroxyglutarate dehydrogenase
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D2-hydroxyglutarate dehydrogenase
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PATHWAY SOURCE
PATHWAYS
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-
SYSTEMATIC NAME
IUBMB Comments
(R)-2-hydroxyglutarate:acceptor 2-oxidoreductase
Contains FAD. The enzyme has no activity with NAD+ or NADP+, and was assayed in vitro using artificial electron acceptors. It has lower activity with (R)-lactate, (R)-2-hydroxybutyrate and meso-tartrate, and no activity with the (S) isomers. The mammalian enzyme is stimulated by Zn2+, Co2+ and Mn2+.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-2-hydroxyglutarate + acceptor
2-oxoglutarate + reduced acceptor
show the reaction diagram
-
-
-
?
(R)-2-hydroxyglutarate + electron transfer flavoprotein
2-oxoglutarate + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
?
(R)-2-hydroxyglutarate + phenazine methosulfate
2-oxoglutarate + reduced phenazine methosulfate
show the reaction diagram
-
-
-
?
additional information
?
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-
description of two pathogenic mutations in the D-2-hydroxyglutarate dehydrogenase gene causing D-2-HGA with a very mild clinical presentation: a splice error (IVS4-2A->G) and a missense mutation (c.1315A->G, p.Asn439Asp). Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause bith the severe and mild phenotypes of D-2-HGA
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-2-hydroxyglutarate + acceptor
2-oxoglutarate + reduced acceptor
show the reaction diagram
-
-
-
?
(R)-2-hydroxyglutarate + electron transfer flavoprotein
2-oxoglutarate + reduced electron transfer flavoprotein
show the reaction diagram
-
-
-
?
additional information
?
-
-
description of two pathogenic mutations in the D-2-hydroxyglutarate dehydrogenase gene causing D-2-HGA with a very mild clinical presentation: a splice error (IVS4-2A->G) and a missense mutation (c.1315A->G, p.Asn439Asp). Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause bith the severe and mild phenotypes of D-2-HGA
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the enzyme elevates 2-oxoglutarate levels, influencing histone and DNA methylation, and HIF1alpha hydroxylation, and induces mitochondrial isocitrate dehydrogenase activity
physiological function
the enzyme directly reduces recombinant human electron transferring flavoprotein (ETF), thus establishing a metabolic link between the oxidation of D-2-hydroxyglutarate and the mitochondrial electron transport chain
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
D2HDH_HUMAN
521
0
56416
Swiss-Prot
Mitochondrion (Reliability: 2)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A208T
inactive
A426T
inactive
G131X
inactive
I147S
D-2-hydroxyglutaric aciduria disease-related variant. The cofactor binding site is compromised by the single amino acid replacement. The variant forms aggregates that are unable to bind the FAD cofactor
R212W
inactive
R421H
inactive
V444A
D-2-hydroxyglutaric aciduria disease-related variant. The cofactor binding site is compromised by the single amino acid replacement. The variant forms aggregates that are unable to bind the FAD cofactor
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of the enzyme is upregulated in the presence of high endogenous concentrations of (S)-2-hydroxyglutarate
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Struys, E.A.; Korman, S.H.; Salomons, G.S.; Darmin, P.S.; Achouri, Y.; van Schaftingen, E.; Verhoeven, N.M.; Jakobs, C.
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria
Ann. Neurol.
58
626-630
2005
Homo sapiens
Manually annotated by BRENDA team
Lin, A.P.; Abbas, S.; Kim, S.W.; Ortega, M.; Bouamar, H.; Escobedo, Y.; Varadarajan, P.; Qin, Y.; Sudderth, J.; Schulz, E.; Deutsch, A.; Mohan, S.; Ulz, P.; Neumeister, P.; Rakheja, D.; Gao, X.; Hinck, A.; Weintraub, S.T.; DeBerardinis, R.J.; Sill, H.; Dahia, P.L.; Aguiar, R.C.
D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2
Nat. Commun.
6
7768
2015
Homo sapiens (Q8N465)
Manually annotated by BRENDA team
Toplak, M.; Brunner, J.; Schmidt, J.; Macheroux, P.
Biochemical characterization of human D-2-hydroxyglutarate dehydrogenase and two disease related variants reveals the molecular cause of D-2-hydroxyglutaric aciduria
Biochim. Biophys. Acta
1867
140255
2019
Homo sapiens (Q8N465), Homo sapiens
Manually annotated by BRENDA team
Berger, R.S.; Ellmann, L.; Reinders, J.; Kreutz, M.; Stempfl, T.; Oefner, P.J.; Dettmer, K.
Degradation of D-2-hydroxyglutarate in the presence of isocitrate dehydrogenase mutations
Sci. Rep.
9
7436
2019
Homo sapiens (Q8N465)
Manually annotated by BRENDA team