Degradation of D-2-hydroxyglutarate in the presence of isocitrate dehydrogenase mutations.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 05 2019
15 05 2019
Historique:
received:
26
09
2018
accepted:
20
03
2019
entrez:
17
5
2019
pubmed:
17
5
2019
medline:
6
11
2020
Statut:
epublish
Résumé
D-2-Hydroxyglutarate (D-2-HG) is regarded as an oncometabolite. It is found at elevated levels in certain malignancies such as acute myeloid leukaemia and glioma. It is produced by a mutated isocitrate dehydrogenase IDH1/2, a low-affinity/high-capacity enzyme. Its degradation, in contrast, is catalysed by the high-affinity/low-capacity enzyme D-2-hydroxyglutarate dehydrogenase (D2HDH). So far, it has not been proven experimentally that the accumulation of D-2-HG in IDH mutant cells is the result of its insufficient degradation by D2HDH. Therefore, we developed an LC-MS/MS-based enzyme activity assay that measures the temporal drop in substrate and compared this to the expression of D2HDH protein as measured by Western blot. Our data clearly indicate, that the maximum D-2-HG degradation rate by D2HDH is reached in vivo, as v
Identifiants
pubmed: 31092874
doi: 10.1038/s41598-019-43891-3
pii: 10.1038/s41598-019-43891-3
pmc: PMC6520482
doi:
Substances chimiques
Glutarates
0
alpha-hydroxyglutarate
2889-31-8
Alcohol Oxidoreductases
EC 1.1.-
IDH2 protein, human
EC 1.1.1.41
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
D2HGDH protein, human
EC 1.1.99.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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