Synonyms: 2-Hydroxyglutaric acid, α-hydroxyglutarate, 2-hydroxyglutarate.
Method(s): GC-MS/MS (1).
What is α-hydroxyglutaric acid?
α-Hydroxyglutaric acid (α-hydroxyglutarate) is formed from α-ketoglutarate in a reaction catalyzed by phosphoglycerate dehydrogenase (PHGDH). α-Hydroxyglutaric acid is also formed by the gain-of-function mutations in isocitrate dehydrogenase (IDH), which have been reported in a wide range of tumours, including acute myeloid leukemia (AML), intrahepatic cholangiocarcinoma, breast carcinoma and glioma. Thus, α-hydroxyglutaric acid has been regarded as an “oncometabolite”, the circulating levels of which may provide diagnostic and prognostic information (2).
Performance of the assay
Lower limit of detection (LOD): na.
Within-day CV: 5 %; between-day CV: na.
Assessment of α-hydroxyglutarate status in patients with IDH mutated malignancies.
Specimen, collection and processing
Patient/subject: No special precaution.
Matrix: Serum or EDTA plasma.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Probably stable.
Transportation; for general instruction on transportation, click here.
Frozen, on dry ice.
Reported values, interpretation
Reported values: 0.15-2 µmol/L, and may be 10-fold higher in cancer patients with the IDH1/2 mutation(s).
Intraclass correlation coefficient (ICC): na.
1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. Ježek, P. (2020). 2-Hydroxyglutarate in cancer cells. Antioxid Redox Signal, in press.