Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise

WW Winder, DG Hardie - American Journal of Physiology …, 1996 - journals.physiology.org
WW Winder, DG Hardie
American Journal of Physiology-Endocrinology and Metabolism, 1996journals.physiology.org
Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle mitochondria, decreases
in rat skeletal muscle during exercise or in response to electrical stimulation. Regulation of
rat skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-
CoA, was studied in vitro and in vivo. Avidin-Sepharose affinity-purified ACC from hindlimb
skeletal muscle was phosphorylated by purified liver AMP-activated protein kinase with a
concurrent decrease in ACC activity. AMP-activated protein kinase was quantitated in …
Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle mitochondria, decreases in rat skeletal muscle during exercise or in response to electrical stimulation. Regulation of rat skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-CoA, was studied in vitro and in vivo. Avidin-Sepharose affinity-purified ACC from hindlimb skeletal muscle was phosphorylated by purified liver AMP-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 from 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.
American Physiological Society