Inactivation of acetyl-coa carboxylase and activation of amp
-activated protein kinase in muscle during exercise.
Winder, W. W., and D. G. Hardie.
Zoology Department, Brigham Young University, Provo, Utah 84602 and
Department of Biochemistry, The University, Dundee, DD1 4HN
Scotland
APStracts 2:0205E, 1995.
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 0-20 mM.
Malonyl-CoA decreased from a resting value of 1.85 + 0.29 nmol/g 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.
Received 22 May 1995; accepted in final form 21 September 1995.
APS Manuscript Number E230-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95