| abstract |
A pharmaceutically-acceptable modulator of the structure, activity, or expression level of an enzyme complex, such as the pyruvate dehydrogenase (PD) complex, in the mitochondria of warm-blooded animals, including humans, and methods of use thereof, comprises an effective amount of at least one lipoic acid derivative and at least one pharmaceutically-acceptable carrier thereof. By preventing the detoxification of toxic metabolites of anaerobic glycolysis through inhibition of the activity of the PD complex ElĪ± subunit, the modulator increases PD kinase activity and concomitantly decreases PD phosphatase activity, obliging increased oxidative phosphorylation activity in the mitochondrion. As a cell characterized by hyperprolif eration, such as a tumor cell, cannot also generate acetyl-CoA and NADH because of the action of the modulator in inhibiting the action of the E2 subunit of the PD complex, the mitochondrial membrane polarization is lost, facilitating cell death. |