Mutations in TCA cycle enzymes can have significant effects on cancer progression. For example, mutations in isocitrate dehydrogenase (IDH) can lead to the production of 2-hydroxyglutarate, an oncometabolite that disrupts cellular differentiation and promotes tumorigenesis. Similarly, mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) result in the accumulation of succinate and fumarate, respectively, which can inhibit prolyl hydroxylases and stabilize HIF-1α, promoting angiogenesis and a more aggressive cancer phenotype.
