AMP-activated protein kinase – a sensor of glycogen as well as AMP and ATP?
Version of Record online: 19 FEB 2009
© 2009 The Authors. Journal compilation © 2009 Scandinavian Physiological Society
Special Issue: THE 5TH INTERNATIONAL SYMPOSIUM ON AMPK 'AMPK IN SICKNESS AND HEALTH - FROM MOLECULE TO MAN'
Volume 196, Issue 1, pages 99–113, May 2009
How to Cite
McBride, A. and Hardie, D. G. (2009), AMP-activated protein kinase – a sensor of glycogen as well as AMP and ATP?. Acta Physiologica, 196: 99–113. doi: 10.1111/j.1748-1716.2009.01975.x
- Issue online: 1 APR 2009
- Version of Record online: 19 FEB 2009
- Received 21 October 2008, accepted 19 January 2009
- AMP-activated protein kinase;
- energy balance;
- glycogen synthase;
- glycogen-binding domains;
The classical role of the AMP-activated protein kinase (AMPK) is to act as a sensor of the immediate availability of cellular energy, by monitoring the concentrations of AMP and ATP. However, the β subunits of AMPK contain a glycogen-binding domain, and in this review we develop the hypothesis that this is a regulatory domain that allows AMPK to act as a sensor of the status of cellular reserves of energy in the form of glycogen. We argue that the pool of AMPK that is bound to the glycogen particle is in an active state when glycogen particles are fully synthesized, causing phosphorylation of glycogen synthase at site 2 and providing a feedback inhibition of further extension of the outer chains of glycogen. However, when glycogen becomes depleted, the glycogen-bound pool of AMPK becomes inhibited due to binding to α16-linked branch points exposed by the action of phosphorylase and/or debranching enzyme. This allows dephosphorylation of site 2 on glycogen synthase by the glycogen-bound form of protein phosphatase-1, promoting rapid resynthesis of glycogen and replenishment of glycogen stores. This is an extension of the classical role of AMPK as a ‘guardian of cellular energy’, in which it ensures that cellular energy reserves are adequate for medium-term requirements. The literature concerning AMPK, glycogen structure and glycogen-binding proteins that led us to this concept is reviewed.