Reduction of oxoglutarate (2OG or alpha-ketoglutarate) to 2-hydroxyglutarate (2HG) is driven by NADPH. 2HG is also formed in side reactions of lactate dehydrogenase and malate dehydrogenase. Millimolar 2HG concentrations are found in some cancer cells compared to , whereas side activities of lactate and malate dehydrogenase form submillimolar s-2-hydroxyglutarate (s-2HG). However, even wild-type IDH1 and IDH2, notably under shifts toward reductive carboxylation glutaminolysis or changes in other enzymes, lead to “intermediate” 0.01–0.1 mM 2HG levels, for example, in breast carcinoma compared with nanomolar concentrations in benign cells. 2HG is considered an important player in reprogramming metabolism of cancer cells.
Reference: Jezek 2020 Antioxid Redox Signal
MitoPedia topics: Substrate and metabolite