α-Hydroxyglutaric acid (2-HG) is an α-hydroxy acid. It is normally metabolized to 2-oxoglutarate by D- and L-2-hydroxyglutarate dehydrogenases, and mutations in these enzymes cause 2-hydroxyglutaric aciduria, a neurometabolic disorder. Recent studies have found that mutations in isocitrate dehydrogenases 1 and 2, typically associated with certain cancers, can cause these enzymes to convert isocitrate to 2-HG, rather than α-ketoglutarate. 2-HG is structurally similar to α-ketoglutarate and competitively inhibits α-ketoglutarate-dependent dioxygenases, including lysine demethylases and DNA hydroxylases.
