The regulation of muscle glycogen: the granule and its proteins

Abstract

Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation.

Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training

“…This hypothesis is based on evidence that muscle glycogen availability is inversely related to muscle cell membrane GLUT4 content during insulin stimulation (Derave et al 2000), glycogen synthase activity (Jensen et al 2006), the expression of GLUT4 mRNA (Steinberg et al 2006), and hence insulin sensitivity (Derave et al 2000;Jensen et al 2006;Kawanaka et al 2000;Laurent et al 2000;Litherland et al 2007;Richter et al 2001). The upregulation of key metabolic genes initiated by the release of glycogen-bound proteins may, at least in part, explain how glycogen depletion affects insulin-dependent muscle glucose uptake (Steinberg et al 2006;Graham et al 2010). Regardless of the potential mechanisms however, if muscle glycogen regulates insulin sensitivity then exercise protocols aiming to reduce glycogen levels should be effective.…”

Physiological Consequences of Compartmentalized Acyl-CoA Metabolism

“…Proteins within these assemblies might interact via their transmembrane and extra-membrane domains or be tethered to scaffolds, in a manner that is regulated by allosteric effectors and post-translational modifications (2,3). Such interactions may be transient, as occurs with the enzymes that comprise purinosomes (4), or they may be semi-permanent as occurs within glycogen granules that contain enzymes that synthesize and degrade glycogen, and their regulatory kinases and phosphatases (5,6). Assemblies of proteins are advantageous because even without a physical tunnel, they can increase reaction rates by enhancing local substrate concentrations, restricting intermediates from entering competing reactions, and stabilizing chemically unstable intermediates.…”

Abnormal Glycogen Storage by Retinal Neurons in Diabetes

“…1 The storage unit for glycogen is the glycogen particle, a highly organized macromolecular complex that may have up to 12 shell-like tiers with a diameter of 42 nm and accommodation for 55,000 glucosyl residues. 1,2 In most instances the particle does not achieve its maximal capacity, and in skeletal muscle the average particle diameter is 25 nm, corresponding to seven tiers. 3,4 The glycogen particle is seeded by a self-glucosylating protein primer called glycogenin, 5 and the current model corresponds to the beta particle 4 in the ultrastructural classification described by Wanson and Drochmans 6 and Drochmans.…”