INACTIVATION OF ACETYL-COA CARBOXYLASE AND ACTIVATION OF AMP-ACTIVATED PROTEIN-KINASE IN MUSCLE DURING EXERCISE

Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle m itochondria, decreases in rat skeletal muscle during exercise or in re sponse to electrical stimulation. Regulation of rat skeletal muscle ac etyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-CoA, w as studied in vitro and in vivo. Avidin+Sepharose affinity-purified AC C from hindlimb skeletal muscle was phosphorylated by purified liver A MP-activated protein kinase with a concurrent decrease in ACC activity . AMP-activated protein kinase was quantitated in resuspended ammonium sulfate precipitates of the fast-twitch red (type IIa fibers) region of the quadriceps muscle. Rats running on a treadmill at 21 m/min up a 15% grade show a 2.4-fold activation of AMP-activated protein kinase concurrently with a marked decrease in ACC activity in the resuspended ammonium sulfate precipitates at all citrate concentrations ranging f rom 0 to 20 mM. Malonyl-CoA decreased from a resting value of 1.85 +/- 0.29 to 0.50 +/- 0.09 nmol/g in red quadriceps muscle after 30 min of treadmill running. The activation of the AMP-activated protein kinase with consequent phosphorylation and inactivation of ACC may be one of the primary events in the control of malonyl-CoA and hence fatty acid oxidation during exercise.