On the other hand, allosteric transcription factors (aTFs) in bacteria have evolved to sense a variety of chemicals 24. Ion mobility-quadrupole-time-of-flight mass spectrometry (IM-QTOF-MS), a powerful tool to separate complex mixtures, may resolve both enantiomers without any derivatization 23. Chiral derivatization with proper reagents is necessary to distinguish d-2-HG from its mirror-image enantiomer l-2-HG by GC-MS/MS and LC-MS/MS 22. Gas chromatography-tandem mass spectrometry (GC-MS/MS) 18, 19 and liquid chromatography-tandem mass spectrometry (LC-MS/MS) 20, 21 are often used to quantitatively assess d-2-HG levels. As such, the detection of d-2-HG is relevant for the diagnosis and monitoring of these diseases 15, 16, 17. However, the regulation of D2HGDH expression is not fully understood, and the mechanism whereby organisms responding to the presence of d-2-HG has not yet been elucidated.ĭ-2-HG levels are increased in patients with d-2-hydroxyglutaric aciduria and IDH mutation-related cancers 1, 2. This suggests that organisms may have evolved specific mechanisms to respond to d-2-HG accumulation by increasing d-2-HG catabolism through enhanced D2HGDH expression 11, 12, 13, 14. d-2-HG is present at rather low levels (< 0.9 μM in the plasma of healthy humans) under physiological conditions 1, 10. d-2-HG dehydrogenase (D2HGDH) catalyzes the conversion of d-2-HG to 2-ketoglutarate (2-KG) and is the key enzyme involved in d-2-HG catabolism 7. It has been reported that d-2-HG may also be an important metabolic intermediate involved in different core metabolic processes, including l-serine synthesis 7, lysine degradation 8, and 4-hydroxybutyrate catabolism 9. Thus, d-2-HG is also considered an oncometabolite. However, recent studies have revealed the accumulation of d-2-HG in many tumor cells due to mutations in isocitrate dehydrogenase 1/2 (IDH1/2) 2, 3, 4, 5, 6.
D-2-Hydroxyglutarate ( d-2-HG) has traditionally been considered an abnormal metabolite associated with the neurometabolic disorder d-2-hydroxyglutaric aciduria ( d-2-HGA) 1.
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