Branched-chain 2-oxo acid dehydrogenase complex activation by tetanic contractions in rat skeletal muscle.
Branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle was activated by muscle contractions elicited by electrical stimulation. This activation was attributed to dephosphorylation of the phosphorylated 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 muscle of the non-stimulated (control) leg, indicating that blood components are not involved in the mechanism of the enzyme activation in the muscle. Adenine nucleotides, branched-chain amino and 2-oxo acids and lactate in the muscle were determined as possible factors modulating the enzyme complex activity through inhibition of branched-chain 2-oxo acid dehydrogenase kinase activity. The profile of enzyme activation induced by muscle contractions was different from the alteration of the adenine nucleotide concentrations but was similar to the alteration of the concentrations of branched-chain amino and 2-oxo acids in the muscle. 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 intracellular branched-chain 2-oxo acids increased by muscle contractions accumulate 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.
Shimomura
Y
Y
Department of Bioscience, Nagoya Institute of Technology, Japan.
Fujii
H
H
Suzuki
M
M
Fujitsuka
N
N
Naoi
M
M
Sugiyama
S
S
Harris
R A
RA
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D004558:Electric Stimulation; D004789:Enzyme Activation; D005260:Female; D007291:Inosine Monophosphate / Q000032:analysis; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction; D051381:Rats; D017207:Rats, Sprague-Dawley
D007773:Lactates; D009097:Multienzyme Complexes; D007291:Inosine Monophosphate; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)