Mitochondria are the cellular powerhouses responsible for producing ATP through oxidative phosphorylation. When mitochondrial function is impaired — whether in cancer, metabolic disease, or inherited disorders — cells shift to less efficient anaerobic glycolysis, producing lactate rather than ATP.

The PDK/PDH axis is the molecular switch that controls this shift. Pyruvate dehydrogenase kinases (PDKs) phosphorylate and inactivate pyruvate dehydrogenase (PDH). When PDH is inactive, pyruvate cannot enter the Krebs cycle and is instead converted to lactate. DCA inhibits PDKs, removing the block on PDH and restoring mitochondrial metabolism.

There are four PDK isoforms (PDK1–4), and DCA inhibits all of them with varying potency. PDK2 and PDK4 are the most sensitive, with IC50 values of approximately 183μM and 80μM respectively.

The result of PDH reactivation is a metabolic shift with multiple downstream consequences: increased mitochondrial membrane depolarisation, increased reactive oxygen species production, increased susceptibility to apoptosis in cells that depend on glycolytic metabolism, and reduced lactate output.

Potassium DCA produces these effects through the identical mechanism as sodium DCA — the counterion does not alter PDK inhibition kinetics.

This article is for informational and educational purposes only. AuraDCA products are intended for research use only.