1GlycogenMost common storage form of glucose in animals, bacteria (yeast)Branched polymer of α1,4- & α1,6-linked glucoseSimilar to amylopectin; but with smaller and more frequent branching: branching every 8-12 residuesIn animals glycogen is stored largely in the liver and muscleIn mammals glycogen can make up ~10% liver mass & 2% of muscle massBCMB 8020 April 13,20062Glycogen use in animalsInsulin glucagon or adrenaline(fasting) (flight or fight)Excess Glucose →→ GLYCOGEN →→replenished glucose(i.e. after feeding)glycogen synthesis glycogenolysis3In vertebrates ~ 2/3 of dietary glucose is converted to glycogentransported in bloodFood → Glucose → intestine → cells→ converted to Glc-6-Pabsorbed hexokinaseliver (GLUT1)muscle (*GLUT4, GLUT 1)*=insulin stimulated4The stimulation of glycogen synthesis is one of the major physiological responses modulated by insulinThe exact mechanism by which insulin stimulates glycogen synthesis is not knownInsulin:* Controls uptake and transport of glucose (GLUT4)* Regulates phosphorylation and activation state of glycogen biosynthetic and catabolic enzymes (glycogen synthase; glycogen phosphorylase)5Steps in Glycogen Synthesis6Synthesis 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 pyrophosphate78Simplified reactions for the bulk of glycogen synthesis9The 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 glucosylationof glycogenin on Tyr194 to form a glycogenin with an average glucan chain of DP 8 (maltooctaose). Steps in glycogen synthesisSelf-glucosylation of glycogenin (~37 kD) on Tyr-194 in a glycosidic linkageUDP-Glc + Proglycogen Synthase + Branching Enzyme →Proglycogen (~ 400,000 daltons; ~DP 2470)Proglycogen + UDP-Glc + Macroglycogen Synthase + Branching Enzyme → Macroglycogen(~ 107 daltons; ~DP 61,728)1011Figure 1. Diagram illustrating the first four tiers of the glycogen granule. Each B chain is linked by α-1–6 glycosidic bonds, whereas each A chain is unbranchedand is linked by α-1–4 glycosidic bonds. G, glycogenin, the self-glycosylatingprotein primer of glycogen. from Shearer: Exerc Sport Sci Rev, Volume 32(3).July 2004.120-126121314Blood [Glc] ~5 mM1516Mechanism of Glycogen PhosphorylaseExample of phosphorolysis1718Figure 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, debranchingenzyme; PP1, protein phosphatase 1. from: Shearer: Exerc Sport Sci Rev, Volume 32(3).July
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