AMP-activated protein kinase (AMPK) in skeletal muscle during physical exercise

Abstract

AMP-activated protein kinase (AMPK) is a phylogenetically conserved serine-threonine protein kinase that plays a major role as fuel-sensing enzyme.As such it stimulates the fatty acid oxidation, glucose uptake and ketogenesis with a concomitant inhibition of lipogenesis and a modulation of insulin secretion. AMPK is mainly expressed in liver, brain and skeletal muscle, tissues where the bioenergetic metabolism is relevant for the physiology of the entire organism. In addition, emerging evidences indicate that the dysregulation of AMPK functions can be associated to the pathogenesis of several diseases including type 2 diabetes and cancer. For these latter properties, AMPK functions turnover has also been considered as a target for specific therapeutic approaches.Considering the skeletal muscle physiology, during physical exercise,the energy demand increases compared to the resting state, and a large amount of ATP is hydrolyzed causing the increase of the AMP/ATP ratio. The increase of intracellular AMP concentration leads to the activation of AMPK thatmodulates the activity of the main regulatory enzymes involved in energy metabolism.The activation of AMPK triggers signaling pathways that lead to the stimulation of energy producing processes (substrates uptake and catabolic pathways)as well as to the inhibition of biosynthetic pathways that need energy expenditure. Moreover, the involvement of AMPK in mitochondrial biogenesis has also been proposed to be relevant in skeletal muscle tissue plasticity. In this mini reviewwe report of the main biochemical and functional properties of AMPK, its activation during physical exercise, focusingon the molecular and cellular effectsin muscle contraction.