Dataset Information


D-2-Hydroxyglutarate producing neo-enzymatic activity inversely correlates with frequency of the type of isocitrate dehydrogenase 1 mutations found in glioma.



IDH mutations frequently occur in diffuse gliomas and result in a neo-enzymatic activity that results in reduction of ?-ketoglutarate to D-2-hydroxyglutarate. In gliomas, the frequency of IDH1 mutations in codon 132 increases in the order R132L-R132S-R132G-R132C-R132H with R132H constituting more than 90% of all IDH1 mutations.


We determined the levels of D-2-hydroxyglutarate in glioma tissues with IDH1 mutations. D-2-hydroxyglutarate levels increased in the order of R132H-R132C-R132S/R132G/R132L. We expressed and purified IDH1 wild type and mutant protein for biochemical characterization. Enzyme kinetics of mutant IDH protein correlated well with D-2-hydroxyglutarate production in cells with R132H exhibiting the highest and R132L the lowest KM for ?-ketoglutarate. Addition of D-2-hydroxyglutarate to the medium of cell lines revealed an inhibitory effect at higher concentrations. Migration of LN229 increased at lower D-2-hydroxyglutarate concentrations while higher concentrations showed no effect.


These findings may suggest natural selection against the rare IDH1R132 mutations in human glioma due to toxicity caused by high levels of D-2-hydroxyglutarate.

PROVIDER: S-EPMC3937031 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4338038 | BioStudies
| S-EPMC4569544 | BioStudies
| S-EPMC6422176 | BioStudies
| S-EPMC6526618 | BioStudies
| S-EPMC3100313 | BioStudies
| S-EPMC3893588 | BioStudies
| S-EPMC6429355 | BioStudies
| S-EPMC7880418 | BioStudies
| S-EPMC4022846 | BioStudies
| S-EPMC4229941 | BioStudies