Thioredoxin reduction dependent on alpha-ketoacid oxidation by alpha-ketoacid dehydrogenase complexes.

The pyruvate and alpha-ketoglutarate dehydrogenase complexes isolated from pig heart mitochondria promote the reduction of thioredoxin in the presence of their alpha-ketoacid substrates, coenzyme A, and free lipoate. Substrate-specific generation of reduced thioredoxin was established by two independent methods, viz. reduction of insulin and thioredoxin reductase-catalyzed NADPH formation. Dihydrolipoate accumulating in the absence of NAD+ is the likely intermediate. A redox function in alpha-ketoacid oxidation provides a potential role for the specific thioredoxins previously identified by us in mitochondria.