Oxoglutarate dehydrogenase complex

By controlling the amount of available reducing equivalents generated by the Krebs cycle, Oxoglutarate dehydrogenase has a downstream regulatory effect on oxidative phosphorylation and ATP production.

[4] When mitochondria are treated with excess hydrogen peroxide, flux through the electron transport chain is reduced, and NADH production is halted.

It is believed that the temporary inhibition of mitochondrial function stems from the reversible glutathionylation of the E2-lipoac acid domain of Oxoglutarate dehydrogenase.

[5] Glutathionylation, a form of post-translational modification, occurs during times of increased concentrations of free radicals, and can be undone after hydrogen peroxide consumption via glutaredoxin.

Oxoglutarate dehydrogenase activity is turned off in the presence of free radicals in order to protect the enzyme from damage.

The temporary inhibition period sparks a stronger up-regulation response, allowing an increased level of oxoglutarate dehydrogenase activity to compensate for the acute stress exposure.

If oxoglutarate dehydrogenase activity is dysfunctional (no adaptive stress compensation), the build-up of glutamate cannot be fixed, and brain pathologies can ensue.

[9] 2-Oxo-glutarate dehydrogenase is an autoantigen recognized in primary biliary cirrhosis, a form of acute liver failure.

[12] This leads to a possibility that the portion of the TCA cycle responsible for causing the build-up of free radical species in the brain of patients is a malfunctioning oxoglutarate dehydrogenase complex.

[13][14] The result is a reduced lipoylation degree of important mitochondrial enzymes, such as oxoglutarate dehydrogenase complex (OGDC).