Question

2-hydroxy-glutarate (2-HD) made by mutant TCA cycle enzyme isocitrate dehydrogenase (IDH) was considered an ”oncometabolite” because it prevented VHL ubiquitination of HIFa.

True or False

Answer 1

2-hydroxy-glutarate (2-HD) made by mutant TCA cycle enzyme isocitrate dehydrogenase (IDH) was considered an ”oncometabolite” because it prevented VHL ubiquitination of HIFa.

The correct answer is

True

Mutations in genes encoding enzymes involved in the tricarboxylic acid (TCA) cycle, such as the isocitrate dehydrogenases 1 and 2 (IDH1/2), are frequently encountered in astrocytomas and secondary glioblastomas, as well as in acute myeloid leukemias; Gain-of-function mutations in IDH1/2 have been shown to stimulate production of the oncogenic metabolite -2-hydroxyglutarate (-2HD), which plays a role in the prevention of VHL ubiquitination of Haifa.