Application

Octyl-α-KG has been used to study its effects on the cell viability and to replenish α-KG levels in human glioblastoma cells.

Biochem/physiol Actions

Octyl-α-KG (Octyl-2KG) is a membrane-permeant precursor form of α-ketoglutarate (α-KG or 2KG) whose downregulation is often seen with concomitant upregulated D-2-hydroxyglutarate (D-2HG) in tumor cells due to mutations in the NADP⁺-dependent isocitrate dehydrogenase genes IDH1 and IDH2, leading to reduced activity of multiple α-KG-dependent dioxygenases. Cellular α-KG delivery by Octyl-α-KG treatment (1-5 mM) is shown to restore cellular demethylase activity following octyl-2-HG (1-50 mM) treatment or IDH1(R132H) mutant expression. Octyl-α-KG also effectively reactivates α-KG-dependent dioxygenases prolyl hydroxylase (PHD) activity in cells with a dysfunctional tricarboxylic acid (TCA) cycle due to succinate dehydrogenase (SDH) and/or fumarate hydratase (FH) deficiency.