α-Ketoglutarate

What is measured?

Synonyms: α-Ketoglutaric acid, 2-ketoglutaric acid, 2-oxoglutaric acid, 2-oxoglutarate.

What is α-ketoglutaric acid?

α-Ketoglutaric acid (α-ketoglutarate) is a keto acid of the Krebs cycle formed from isocitrate in a reaction catalyzed by isocitrate dehydrogenase (IDH), and further metabolized to succinate through the action of the thiamine pyrophosphate (TPP)-dependent enzyme, α-ketoglutarate dehydrogenase. About 60 α-ketoglutarate-dependent dioxygenases have been identified in humans. These iron-dependent enzymes are involved in a variety of processes, including collagen stabilization, hypoxia, epigenetic regulation and DNA repair (2). Circulating α-ketoglutarate has been associated with heart failure, obesity, diabetes and ageing.

Indication(s)

α-Ketoglutaric acid may be a marker of thiamine deficiency.
The α-ketoglutarate:glutamate ratio is a putative marker of vitamin B6 status.

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

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 2-20 µmol/L. The concentration decreases by age.
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. Herr, C. Q., and Hausinger, R. P. (2018). Amazing diversity in biochemical roles of Fe(II)/2-oxoglutarate oxygenases. Trends Biochem Sci, 43, 517-532.

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