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 HIF alpha

true or false

Answer 1

Thus statement is true .

In presence of oxygen, HIF-α is hydroxylated by prolyl hydroxylase on  prolyl residues . Later this hydroxylated residue is bind with Von Hippel-Lindau protein , which leads to ubiquitination of the protein and HIF-α degradation in proteasomes .

Research has shown that in cancer she to presence of mutant IDH, 2 Hydroxy gluterate formed which inhibits the prolyl hydroxylase thus binding with VHL and its proteosomal degradation. Thus in absence of oxygen these is stability of HiG 1 alpha.

On one hand, research has shown that 2-HG inhibits prolyl hydroxylase. A study conducted by Xu et al. [