The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity

Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell’s change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cells. In this review, we will discuss the manifold roles that this TCA enzyme and its substrate play in cancer

Effects of long-term oxygen treatment on <it>α</it>-ketoglutarate dehydrogenase activity and oxidative modifications in mitochondria of the guinea pig heart

<p>Abstract</p> <p>Objective</p> <p>Oxygen therapy is used for the treatment of various diseases, but prolonged exposure to high concentrations of O₂is also associated with formation of free radicals and oxidative damage.</p> <p>Methods</p> <p>In the present study we compared α-ketoglutarate dehydrogenase (KGDH) activity and mitochondrial oxidative damage in the hearts of guinea pigs after long-term (17 and 60 h) oxygenation with 100% normobaric O₂and with partially negatively (O_{2 neg}) or positively (O_{2 posit}) ionized oxygen.</p> <p>Results</p> <p>Inhalation of O₂led to significant loss in KGDH activity and thiol group content and accumulation of bityrosines. Inhalation of O_{2 neg}was accompanied by more pronounced KGDH inhibition, possibly due to additional formation of protein-lipid conjugates. In contrast, O₂posit prevented loss in KGDH activity and diminished mitochondrial oxidative damage.</p> <p>Conclusions</p> <p>These findings suggest that oxygen treatment is associated with impairment of heart energy metabolism and support the view that inhalation of O_{2 posit}optimizes the beneficial effects of oxygen therapy.</p