However, the increase in α-ketoglutarate levels during hypoxia is followed by an increase of 2-hydroxyglutarate (2HG) production by lactate dehydrogenase A in cells with wild-type IDH1 and IDH2. 2-hydroxyglutarate has been considered an oncometabolite, since it can block tumor cell differentiation, maybe because of its potential inhibition of α-ketoglutarate-dependent enzymes such as TETs and JMJDs [58,94]. This evidence concerns the gene IDH1 and neoplasm.