Regulation of glycogen metabolism, muscle

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Regulation of glycogen metabolism, liver

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Description

Intracellular glycogen stores contribute to blood-glucose homeostasis during fasting, provide energy for muscle contraction and support a broad range of cellular activities in many tissues. Glycogen synthase and glycogen phosphorylase control glycogen synthesis and breakdown, respectively. Glycogen phosphorylases, including the liver, muscle and brain forms PYGL, PYGM and PYGB, catalyse glycogen breakdown to glucose-1-phosphate.

The muscle map represents regulation through insulin signalling, adrenergic signalling and calcium-dependent activation of phosphorylase kinase. Epinephrine activates the ADRB2-Gs-adenylate cyclase-cAMP-PKA pathway, promoting phosphorylation and activation of muscle glycogen phosphorylase PYGM, while insulin signalling through PI3K-PDPK1-AKT2 regulates glycogen synthase through inhibition of GSK3B.

The liver map represents complementary regulation by insulin and glucagon. Glucagon signalling through GCGR activates the Gs-adenylate cyclase-cAMP-PKA pathway and promotes glycogen utilisation, whereas insulin signalling favours glycogen synthesis. In liver, the corresponding major metabolic enzymes are glycogen synthase GYS2 and glycogen phosphorylase PYGL.

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Contributors

Vasundra Touré1,2, Luiz Ladeira3, Tatiana Serebriyskaya4, Valeriya Berzhitskaya4, Alexander Mazein5,6, John Albanese7

Affiliations
  1. 1Norwegian University of Science and Technology, Trondheim, Norway
  2. 2SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
  3. 3Biomechanics Research Unit, GIGA In Silico Medicine, University of Liège, Liège, Belgium
  4. 4Systems Biology and Translational Medicine, EPAM Systems, Inc., Newtown, USA
  5. 5Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg
  6. 6Department of Cancer Research, Luxembourg Institute of Health, Strassen, Luxembourg
  7. 7University of Connecticut School of Medicine, Farmington, USA