BCMB 8020 April 13 2006 Glycogen use in animals Glycogen Most common storage form of glucose in animals bacteria yeast Branched polymer of 1 4 1 6 linked glucose Similar to amylopectin but with smaller and more frequent branching branching every 8 12 residues Insulin glucagon or adrenaline fasting flight or fight Excess Glucose GLYCOGEN replenished glucose i e after feeding glycogen synthesis glycogenolysis In animals glycogen is stored largely in the liver and muscle In mammals glycogen can make up 10 liver mass 2 of muscle mass In vertebrates 2 3 of dietary glucose is converted to glycogen transported in blood Food Glucose intestine cells converted to Glc 6 P absorbed hexokinase liver GLUT1 muscle GLUT4 GLUT 1 insulin stimulated The stimulation of glycogen synthesis is one of the major physiological responses modulated by insulin The exact mechanism by which insulin stimulates glycogen synthesis is not known Insulin Controls uptake and transport of glucose GLUT4 Regulates phosphorylation and activation state of glycogen biosynthetic and catabolic enzymes glycogen synthase glycogen phosphorylase Steps in Glycogen Synthesis Synthesis of the chemically activated substrate for glycogen synthesis UDP Glc by UDP Glc pyrophosphorylase Luis Leloir discovered NDP sugars The synthesis of UDP Glc is driven by the subsequent hydrolysis of pyrophosphate 1 Simplified reactions for the bulk of glycogen synthesis The question of how glycogen synthesis was initiated remained open for many years It is now known that glycogen synthesis begins by the Mn dependent self glucosylation of glycogenin on Tyr194 to form a glycogenin with an average glucan chain of DP 8 maltooctaose Steps in glycogen synthesis Self glucosylation of glycogenin 37 kD on Tyr 194 in a glycosidic linkage UDP Glc Proglycogen Synthase Branching Enzyme Proglycogen 400 000 daltons DP 2470 Proglycogen UDP Glc Macroglycogen Synthase Branching Enzyme Macroglycogen 107 daltons DP 61 728 Figure 1 Diagram illustrating the first four tiers of the glycogen granule Each B chain is linked by 1 6 glycosidic bonds whereas each A chain is unbranched and is linked by 1 4 glycosidic bonds G glycogenin the self glycosylating protein primer of glycogen from Shearer Exerc Sport Sci Rev Volume 32 3 July 2004 120 126 2 Blood Glc 5 mM Mechanism of Glycogen Phosphorylase Example of phosphorolysis Figure 7 Proposed scheme of glycogen granule formation in skeletal muscle A i Glycogenin initiates glycogen granule formation at the sarcolemmal membrane ii once initiation is complete glycogen synthase attaches to the granule resulting in its growth iii as soon as granules are of sufficient size other glycogen metabolizing enzymes attach to the granule iv glycogen synthase dissociates from the mature granule and returns to the sarcolemmal membrane whereas the granule is translocated to its final location on actin filaments B Incoming glucose is transported to the site of the granule Here initiation and the association of other proteins in the glycosome occur at the site of final granule location G glycogenin GP glycogen phosphorylase GS glycogen synthase BE branching enzyme DE debranching enzyme PP1 protein phosphatase 1 from Shearer Exerc Sport Sci Rev Volume 32 3 July 2004 120 126 3
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