Correct option is D
In cancers such as glioblastomas, oligodendrogliomas, and astrocytomas, mutations in the enzyme isocitrate dehydrogenase (IDH) lead to the conversion of isocitrate into the oncometabolite 2-hydroxyglutarate. This oncometabolite accumulates in the cells and has been shown to disrupt normal cellular metabolism. One of its key effects is the inhibition of enzymes that require α-ketoglutarate, a critical molecule in the tricarboxylic acid (TCA) cycle, for their function. α-Ketoglutarate is involved in multiple enzymatic reactions, and its inhibition by 2-hydroxyglutarate can disrupt normal cellular processes, contributing to the oncogenic behavior of these cancers.
Information Booster:
- 2-hydroxyglutarate is a potent oncometabolite that acts by inhibiting α-ketoglutarate-dependent enzymes, such as those involved in epigenetic regulation (e.g., histone demethylases and TET enzymes). Its accumulation is a hallmark of IDH-mutant cancers.
- The disruption of α-ketoglutarate’s function impacts many cellular processes, including DNA and histone modifications, which play a role in cancer development and progression.
Additional Information:
- 2-hydroxybutyrate, α-ketoglutarate: This combination is not correct. 2-hydroxybutyrate is a different metabolite and does not play a significant role in IDH mutation-related cancer progression in the same way as 2-hydroxyglutarate.
- 2-hydroxyglutarate, succinate: Succinate is another metabolite that can accumulate in cells with mutations in other enzymes (e.g., SDH, fumarate hydratase), but it is not relevant to the context of IDH mutations.
- 2-hydroxyglutarate, 2-hydroxybutyrate: While both metabolites contain "hydroxy" groups, 2-hydroxybutyrate is not the metabolite that accumulates due to IDH mutations in cancer cells.
