Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle.
Winder, W. W.
Department of Zoology, Brigham Young University, Provo, Utah 84602
APStracts 8:0292A, 2001.
AMP-activated protein kinase (AMPK) is emerging as an important energy-
sensing/signaling system in skeletal muscle. This kinase is activated allosterically by 5'-
AMP and inhibited allosterically by creatine phosphate. Phosphorylation of AMPK by an
upstream kinase, AMPK kinase (also activated allosterically by 5'-AMP), results in
activation. It is activated in both rat and human muscle in response to muscle contraction,
the extent of activation depending on work rate and muscle glycogen concentration.
AMPK can also be activated chemically in resting muscle with 5-aminoimidazole-4-
carboxamide-riboside, which enters the muscle and is phosphorylated to form ZMP, a
nucleotide that mimics the effect of 5'-AMP. Once activated, AMPK is hypothesized to
phosphorylate proteins involved in triggering fatty acid oxidation and glucose uptake.
Evidence is also accumulating for a role of AMPK in inducing some of the adaptations to
endurance training, including the increase in muscle GLUT4, hexokinase, uncoupling
protein 3, and some of the mitochondrial oxidative enzymes. It thus appears that AMPK
has the capability of monitoring intramuscular energy charge and then acutely stimulating
fat oxidation and glucose uptake to counteract the increased rates of ATP utilization
during muscle contraction. In addition, this system may have the capability of enhancing
capacity for ATP production when the muscle is exposed to endurance training.
APS Manuscript Number A248-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001