α-Hydroxyglutaric acid



Synonyms: 2-Hydroxyglutaric acid, α-hydroxyglutarate, 2-hydroxyglutarate.
Method(s): GC-MS/MS (1).

What is measured on the same platform, click here.
Platform B: MMA, tHcy, tCys, Met, Ser, Gly, Cysta, Sarc, His, Trp, Kyn, (KTR), HK, KA, XA, AA, HAA, NA, PA, Figlu, Orn, Asp, Glu, Lys, Ala, Phe, Ile, Leu, Pro, Val, Asn, Gln, Thr, Tyr, aKG, aHG, 3HIB, aHB, bHB, AcAc, CML, CEL, 2AAA, BAIBA

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.

Indication(s)

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.

Literature

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.