BRANCHED-CHAIN 2-OXO ACID DEHYDROGENASE COMPLEX ACTIVATION BY TETANICCONTRACTIONS IN RAT SKELETAL-MUSCLE

Branchcd-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle was activated by muscle contractions elicited by electrical stimulati on. This activation was attributed to dephosphorylation of the phospho rylated enzyme complex, and the total enzyme activity was not altered by muscle contractions. The activation of the enzyme complex occurred in the muscle of the electrically stimulated leg, but not in the muscl e of the non-stimulated (control) leg, indicating that blood component s are not involved in the mechanism of the enzyme activation in the mu scle. Adenine nucleotides, branched-chain amino and 2-oxo acids and la ctate in the muscle were determined as possible factors modulating the enzyme complex activity through inhibition of branched-chain 2-oxo ac id dehydrogenase kinase activity. The profile of enzyme activation ind uced by muscle contractions was different from the alteration of the a denine nucleotide concentrations but was similar to the alteration of the concentrations of branched-chain amino and 2-oxo acids in the musc le. The lactate concentration in the stimulated muscle was elevated 3- 5-fold during the contractions, indicating intracellular acidification . Previous studies have shown that the 2-oxo acid derived from leucine is a potent inhibitor of the kinase. These results suggest that intra cellular branched-chain 2-oxo acids increased by muscle contractions a ccumulate in the mitochondria due to exercise-induced acidification of the muscle cell, resulting in activation of branched-chain 2-oxo acid dehydrogenase complex by inhibition of the kinase.