{"id":438,"date":"2019-04-16T07:31:56","date_gmt":"2019-04-16T07:31:56","guid":{"rendered":"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/?post_type=chapter&#038;p=438"},"modified":"2019-04-16T08:40:05","modified_gmt":"2019-04-16T08:40:05","slug":"regulation-of-glycogen-synthesis","status":"publish","type":"chapter","link":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/chapter\/regulation-of-glycogen-synthesis\/","title":{"rendered":"Regulation of glycogen synthesis"},"content":{"raw":"<div><span style=\"float: right\"><a href=\"https:\/\/youtu.be\/fCXkcTWaVkg\" target=\"_blank\" rel=\"noopener\"><img src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"epgp books\" width=\"75px\" height=\"75px;\" \/><\/a>\r\n<\/span><\/div>\r\n<strong>\u00a0 \u00a0 <\/strong>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>Regulation of glycogen synthesis<\/strong>\r\n\r\n&nbsp;\r\n\r\n<strong>Objectives<\/strong>\r\n<ol>\r\n \t<li>To understand regulation of glycogenesis by covalent modification of the glycogen synthase enzyme.<\/li>\r\n \t<li>To understand regulation of glycogenolysis by allosteric control of the glycogen synthase enzyme.<\/li>\r\n \t<li>Role of hormones in regulation of glycogen synthesis.<\/li>\r\n<\/ol>\r\n<strong>\u00a0 \u00a0 <\/strong>\r\n\r\n<strong>Introduction<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">In vertebrates and many microorganisms, surplus glucose is converted to glycogen.<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>A number of microorganisms gather carbon and energy reserves to manage with the starvation conditions provisionally found in the surroundings.<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Organisms accumulate carbon in the form of polysaccharides. Such polysaccharides have high molecular weights. Glycogen has little effect on the internal osmotic pressure in the cell.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Synthesis of glycogen is a main policy for such metabolic storage. Glycogen is a main reserve polysaccharide found inside the cellular environment. Glycogen consists of \u03b1-1, 4- linked glucose subunits with \u03b1-1, 6-linked glucose at the branching points.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Simultaneous synthesis and breakdown of glycogen results into hydrolysis of UTP glucose. It results in to futile cycle. Due to this reason, it is very important to control these pathways.<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-439\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227.png\" alt=\"\" width=\"425\" height=\"149\" \/>\r\n<h2 style=\"text-align: center\"><strong>Fig: 27.1\u00a0 Hydrolysis of UTP occurs on simultaneous glycogen synthesis and breakdown.<\/strong><\/h2>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogen is stored in muscle and liver. Glycogen is stored as large particles. These large particles contain regulatory enzymes and enzyme that mobilize glycogen.<\/li>\r\n<\/ul>\r\n<strong>\u00a0 \u00a0<\/strong>\r\n\r\n<strong>Overview of Glycogen synthesis<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogenesis and glycogenolysis occur by different pathways. Glycogen synthesis involves the use of an activated form of glucose. Mammals, fungi and eukaryotic heterotrophic microorganisms use UDP-Glucose while bacteria and photosynthetic eukaryotes use ADP-Glucose.<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Initially glucose is phosphorylated to glucose 6-phosphate. This reaction is catalyzed by hexokinase (muscle) or glucokinase ( liver).<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Phosphoglucomutase catalyse the isomerisation of Glucose 6-phosphate to glucose 1-phosphate.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Now UDP-glucose pyrophosphorylase catalyse the formation of UDP-glucose fromUTP and glucose 1-phosphate.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogen synthase transfers the glucosyl residue from UDP-glucose to the non reducing terminal residues of glycogen. It is transferred to hydroxyl terminal of C4 end of glycogen to form an \u03b1-1\u20134 glycosidic bond.<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-440\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228.png\" alt=\"\" width=\"488\" height=\"26\" \/>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogen synthase catalyzes only \u03b1- 1\u20134 glycosidic bonds. It results in to the formation of \u03b1- amylose. Branching is catalysed by separate enzyme called Branching enzyme. It is also known as amylo-(1\u20134\u21921\u20136) transglycosylase.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Students may refer module 25 (glycogenesis) for further details.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>Mechanism of regulation<\/strong>\r\n<ul>\r\n \t<li>Covalent modification of Glycogen synthase<\/li>\r\n \t<li>Allosteric control of Glycogen synthase<\/li>\r\n \t<li>Hormonal control: Inhibition of glycogen synthesis by adrenaline and glucagon<\/li>\r\n \t<li>Hormonal control : stimulation of glycogen synthesis by insulin<\/li>\r\n<\/ul>\r\n<strong>\u00a0 \u00a0 <\/strong>\r\n\r\n<strong>Covalent modification of Glycogen synthase<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogen synthase enzyme exists in two forms. They are <strong>Glycogen synthasea<\/strong>and<strong>Glycogen<\/strong> <strong>synthaseb<\/strong>. Glycogen synthase a is an active form of an enzyme while Glycogen synthase b is normally inactive form of an enzyme. <strong>Glycogen synthaseb<\/strong> is converted in to <strong>Glycogen<\/strong> <strong>synthasea <\/strong>by the process of dephosphorylation. It is catalysed by<strong> Protein phosphatase<\/strong>.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Active Glycogen synthase, i.e. dephosphorylated glycogen synthase, is converted back in to inactive phosphorylated glycogen synthase by the process of phosphorylation. It is catalyzed by enzyme <strong>Protein kinase A<\/strong>.<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-441\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229.png\" alt=\"\" width=\"607\" height=\"293\" \/>\r\n<h2 style=\"text-align: center\"><strong>Fig27. 2 Regulation of <\/strong>glycogensynthase<strong> activity<\/strong><\/h2>\r\n&nbsp;\r\n\r\n<strong>Allosteric control of Glycogen synthase<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">High concentration of Glucose 6-phosphate activates glycogen synthase b. Glucose-6-phosphate concentration is low during muscle contraction. Therefore activity of glycogen synthase b is inhibited. During muscular contraction phosphorylase b ismore active (refer glycogen breakdown). Therefore during muscular exercise glycogen degradation promoted while glycogensynthesis is inhibited. This is important for preventing futile cycle.<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>ATP and glucose 6-phosphate concentration is high during resting stage. This condition inhibits activity of phosphorylase b (refer glycogen breakdown) whereas glycogen synthase is activated to restore the glycogen.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glucose-6-phosphate does not affect Glycogen synthase a. Therefore Glycogen synthase a form is active and does not affected by the concentration of glucose 6-phosphate.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>High concentration of AMP, low concentration of ATP and Glucose-6-phosphate<\/strong>\r\n\r\n<img class=\"aligncenter size-full wp-image-444\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230.png\" alt=\"\" width=\"527\" height=\"233\" \/>\r\n\r\n<strong>High concentration of ATP and glucose-6-phosphate.Low concentration of AMP<\/strong>\r\n\r\n&nbsp;\r\n<h2 style=\"text-align: center\"><strong>Fig. 27.3 Regulation of Muscle glycogen phosphorylase b activity<\/strong><\/h2>\r\n&nbsp;\r\n\r\n<strong>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0Elevated concentration of G6P<\/strong>\r\n\r\n<img class=\"aligncenter size-full wp-image-445\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231.png\" alt=\"\" width=\"524\" height=\"224\" \/>\r\n<p style=\"text-align: center\"><strong>Low concentration of glucose-6-phosphate.<\/strong><\/p>\r\n\r\n<h2 style=\"text-align: center\"><strong>Fig. 27.4 Regulation of glycogen synthase b activity<\/strong><\/h2>\r\n<strong>\u00a0 \u00a0 Hormonal control: Adrenalin inhibits the glycogen synthesis<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Glycogenesis and glycogenolysis is regulated by hormones. When level of blood glucosefalll, \u03b1 cells of pancreases secretes the glucagon. Glucagon stimulates glycogenolysis inside the liver. Glycogenolysis releases glucose into the bloodstream to improve blood glucose levels again. \u2018Flight or fight\u2019 response stimulates the adrenal medulla to releases adrenaline (epinephrine).<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Adrenaline binds to the \u03b2-adrenergic receptor on theplasma membrane of the target cell. It causes a conformational change in the protein. It activates a G-protein, which in turn activates the adenylate cyclase enzyme. Activated adenylate cyclase convertsATP to 3\u20195\u2019 cyclic AMP (cAMP).<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Cyclic AMP acts as a second messenger. The cAMP binds to cAMP-dependent protein kinase (PKA).The active protein kinase A phosphorylates phosphorylase kinase. Phosphorylated phosphorylase kinase is active form of phosphorylase kinase. It phosphorylates serine residue in phosphorylase b, whichconverts it into phosphorylase a, that is a more active form.This promotes the glycogenolysis<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Active Glycogen synthase, i.e. dephosphorylated glycogen synthase, is converted back in to inactive phosphorylated glycogen synthase by the process of phosphorylation. It is catalyzed by enzyme <strong>Protein kinase A<\/strong>.<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-446\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232.png\" alt=\"\" width=\"319\" height=\"444\" \/>\r\n\r\n<img class=\"aligncenter size-full wp-image-447\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233.png\" alt=\"\" width=\"601\" height=\"327\" \/>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n<table>\r\n<tbody>\r\n<tr>\r\n<td><strong>you can view video on Regulation of glycogen synthesis<\/strong><\/td>\r\n<td><a href=\"https:\/\/youtu.be\/fCXkcTWaVkg\" target=\"_blank\" rel=\"noopener\"><img class=\"alignnone wp-image-120\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"\" width=\"36\" height=\"36\" \/><\/a><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n&nbsp;\r\n<div class=\"textbox learning-objectives\">\r\n<h3>References<\/h3>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Peter J. Roach, Anna A. Depaoli-Roach, Thomas D. Hurley, Vincent S. Tagliabracci (2012) Glycogen and its metabolism: some new developments and old themes. Biochemical Journal, 441 (3) 763-787; DOI: 10.1042\/BJ20111416<\/li>\r\n \t<li style=\"text-align: justify\">Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS (2012) Glycogen and its metabolism: some new developments and old themes. Biochem J 441: 763\u2013787. doi: 10.1042\/BJ20111416<\/li>\r\n \t<li style=\"text-align: justify\">Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, et al. Regulation of glycogen metabolism in yeast and bacteria. Fems Microbiol Rev. 2010;34(6):952\u2013985.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n<strong>Web site<\/strong>\r\n<ul>\r\n \t<li><a href=\"http:\/\/www.wiley.com\/college\/fob\/quiz\/quiz15\/15-20.swf\">http:\/\/www.wiley.com\/college\/fob\/quiz\/quiz15\/15-20.swf<\/a><\/li>\r\n \t<li><a href=\"https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/Glycogen%20Metabolism.pdf\">https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/Glycogen%20Metabolism.pdf<\/a><\/li>\r\n \t<li><a href=\"http:\/\/themedicalbiochemistrypage.org\/glycogen.php\">http:\/\/themedicalbiochemistrypage.org\/glycogen.php<\/a><\/li>\r\n \t<li><a href=\"https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Glycogenesis\">https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Gly<\/a> <a href=\"https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Glycogenesis\">cogenesis<\/a><\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n<strong>Books<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Harper\u2019sIllustrated Biochemistry by Robert K.. Murray, Daryl K. Granner, Peter A. Mayes, 26th Edition (2003)<\/li>\r\n \t<li style=\"text-align: justify\">Lehninger\u2019S Principle of Biochemistry David L. Nelson and Michael M. Cox,5th Edition (2008)<\/li>\r\n \t<li style=\"text-align: justify\">Instant Notes: Biochemistry, 2nd Edition, B.D. Hames &amp; N. M. Hooper (2005)<\/li>\r\n \t<li style=\"text-align: justify\">Textbook of Biochemistry, 4th Edition Donald Voet, Judith G. Voet (2011)<\/li>\r\n<\/ul>\r\n<\/div>\r\n&nbsp;\r\n\r\n&nbsp;","rendered":"<div><span style=\"float: right\"><a href=\"https:\/\/youtu.be\/fCXkcTWaVkg\" target=\"_blank\" rel=\"noopener\"><img decoding=\"async\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"epgp books\" width=\"75px\" height=\"75px;\" \/><\/a><br \/>\n<\/span><\/div>\n<p><strong>\u00a0 \u00a0 <\/strong><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Regulation of glycogen synthesis<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Objectives<\/strong><\/p>\n<ol>\n<li>To understand regulation of glycogenesis by covalent modification of the glycogen synthase enzyme.<\/li>\n<li>To understand regulation of glycogenolysis by allosteric control of the glycogen synthase enzyme.<\/li>\n<li>Role of hormones in regulation of glycogen synthesis.<\/li>\n<\/ol>\n<p><strong>\u00a0 \u00a0 <\/strong><\/p>\n<p><strong>Introduction<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">In vertebrates and many microorganisms, surplus glucose is converted to glycogen.<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>A number of microorganisms gather carbon and energy reserves to manage with the starvation conditions provisionally found in the surroundings.<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Organisms accumulate carbon in the form of polysaccharides. Such polysaccharides have high molecular weights. Glycogen has little effect on the internal osmotic pressure in the cell.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Synthesis of glycogen is a main policy for such metabolic storage. Glycogen is a main reserve polysaccharide found inside the cellular environment. Glycogen consists of \u03b1-1, 4- linked glucose subunits with \u03b1-1, 6-linked glucose at the branching points.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Simultaneous synthesis and breakdown of glycogen results into hydrolysis of UTP glucose. It results in to futile cycle. Due to this reason, it is very important to control these pathways.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-439\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227.png\" alt=\"\" width=\"425\" height=\"149\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227.png 425w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227-300x105.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227-65x23.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227-225x79.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-227-350x123.png 350w\" sizes=\"auto, (max-width: 425px) 100vw, 425px\" \/><\/p>\n<h2 style=\"text-align: center\"><strong>Fig: 27.1\u00a0 Hydrolysis of UTP occurs on simultaneous glycogen synthesis and breakdown.<\/strong><\/h2>\n<ul>\n<li style=\"text-align: justify\">Glycogen is stored in muscle and liver. Glycogen is stored as large particles. These large particles contain regulatory enzymes and enzyme that mobilize glycogen.<\/li>\n<\/ul>\n<p><strong>\u00a0 \u00a0<\/strong><\/p>\n<p><strong>Overview of Glycogen synthesis<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">Glycogenesis and glycogenolysis occur by different pathways. Glycogen synthesis involves the use of an activated form of glucose. Mammals, fungi and eukaryotic heterotrophic microorganisms use UDP-Glucose while bacteria and photosynthetic eukaryotes use ADP-Glucose.<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Initially glucose is phosphorylated to glucose 6-phosphate. This reaction is catalyzed by hexokinase (muscle) or glucokinase ( liver).<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Phosphoglucomutase catalyse the isomerisation of Glucose 6-phosphate to glucose 1-phosphate.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Now UDP-glucose pyrophosphorylase catalyse the formation of UDP-glucose fromUTP and glucose 1-phosphate.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Glycogen synthase transfers the glucosyl residue from UDP-glucose to the non reducing terminal residues of glycogen. It is transferred to hydroxyl terminal of C4 end of glycogen to form an \u03b1-1\u20134 glycosidic bond.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-440\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228.png\" alt=\"\" width=\"488\" height=\"26\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228.png 488w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228-300x16.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228-65x3.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228-225x12.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-228-350x19.png 350w\" sizes=\"auto, (max-width: 488px) 100vw, 488px\" \/><\/p>\n<ul>\n<li style=\"text-align: justify\">Glycogen synthase catalyzes only \u03b1- 1\u20134 glycosidic bonds. It results in to the formation of \u03b1- amylose. Branching is catalysed by separate enzyme called Branching enzyme. It is also known as amylo-(1\u20134\u21921\u20136) transglycosylase.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Students may refer module 25 (glycogenesis) for further details.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Mechanism of regulation<\/strong><\/p>\n<ul>\n<li>Covalent modification of Glycogen synthase<\/li>\n<li>Allosteric control of Glycogen synthase<\/li>\n<li>Hormonal control: Inhibition of glycogen synthesis by adrenaline and glucagon<\/li>\n<li>Hormonal control : stimulation of glycogen synthesis by insulin<\/li>\n<\/ul>\n<p><strong>\u00a0 \u00a0 <\/strong><\/p>\n<p><strong>Covalent modification of Glycogen synthase<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">Glycogen synthase enzyme exists in two forms. They are <strong>Glycogen synthasea<\/strong>and<strong>Glycogen<\/strong> <strong>synthaseb<\/strong>. Glycogen synthase a is an active form of an enzyme while Glycogen synthase b is normally inactive form of an enzyme. <strong>Glycogen synthaseb<\/strong> is converted in to <strong>Glycogen<\/strong> <strong>synthasea <\/strong>by the process of dephosphorylation. It is catalysed by<strong> Protein phosphatase<\/strong>.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Active Glycogen synthase, i.e. dephosphorylated glycogen synthase, is converted back in to inactive phosphorylated glycogen synthase by the process of phosphorylation. It is catalyzed by enzyme <strong>Protein kinase A<\/strong>.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-441\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229.png\" alt=\"\" width=\"607\" height=\"293\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229.png 607w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229-300x145.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229-65x31.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229-225x109.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-229-350x169.png 350w\" sizes=\"auto, (max-width: 607px) 100vw, 607px\" \/><\/p>\n<h2 style=\"text-align: center\"><strong>Fig27. 2 Regulation of <\/strong>glycogensynthase<strong> activity<\/strong><\/h2>\n<p>&nbsp;<\/p>\n<p><strong>Allosteric control of Glycogen synthase<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">High concentration of Glucose 6-phosphate activates glycogen synthase b. Glucose-6-phosphate concentration is low during muscle contraction. Therefore activity of glycogen synthase b is inhibited. During muscular contraction phosphorylase b ismore active (refer glycogen breakdown). Therefore during muscular exercise glycogen degradation promoted while glycogensynthesis is inhibited. This is important for preventing futile cycle.<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>ATP and glucose 6-phosphate concentration is high during resting stage. This condition inhibits activity of phosphorylase b (refer glycogen breakdown) whereas glycogen synthase is activated to restore the glycogen.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Glucose-6-phosphate does not affect Glycogen synthase a. Therefore Glycogen synthase a form is active and does not affected by the concentration of glucose 6-phosphate.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>High concentration of AMP, low concentration of ATP and Glucose-6-phosphate<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-444\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230.png\" alt=\"\" width=\"527\" height=\"233\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230.png 527w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230-300x133.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230-65x29.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230-225x99.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-230-350x155.png 350w\" sizes=\"auto, (max-width: 527px) 100vw, 527px\" \/><\/p>\n<p><strong>High concentration of ATP and glucose-6-phosphate.Low concentration of AMP<\/strong><\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"text-align: center\"><strong>Fig. 27.3 Regulation of Muscle glycogen phosphorylase b activity<\/strong><\/h2>\n<p>&nbsp;<\/p>\n<p><strong>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0Elevated concentration of G6P<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-445\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231.png\" alt=\"\" width=\"524\" height=\"224\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231.png 524w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231-300x128.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231-65x28.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231-225x96.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-231-350x150.png 350w\" sizes=\"auto, (max-width: 524px) 100vw, 524px\" \/><\/p>\n<p style=\"text-align: center\"><strong>Low concentration of glucose-6-phosphate.<\/strong><\/p>\n<h2 style=\"text-align: center\"><strong>Fig. 27.4 Regulation of glycogen synthase b activity<\/strong><\/h2>\n<p><strong>\u00a0 \u00a0 Hormonal control: Adrenalin inhibits the glycogen synthesis<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">Glycogenesis and glycogenolysis is regulated by hormones. When level of blood glucosefalll, \u03b1 cells of pancreases secretes the glucagon. Glucagon stimulates glycogenolysis inside the liver. Glycogenolysis releases glucose into the bloodstream to improve blood glucose levels again. \u2018Flight or fight\u2019 response stimulates the adrenal medulla to releases adrenaline (epinephrine).<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Adrenaline binds to the \u03b2-adrenergic receptor on theplasma membrane of the target cell. It causes a conformational change in the protein. It activates a G-protein, which in turn activates the adenylate cyclase enzyme. Activated adenylate cyclase convertsATP to 3\u20195\u2019 cyclic AMP (cAMP).<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Cyclic AMP acts as a second messenger. The cAMP binds to cAMP-dependent protein kinase (PKA).The active protein kinase A phosphorylates phosphorylase kinase. Phosphorylated phosphorylase kinase is active form of phosphorylase kinase. It phosphorylates serine residue in phosphorylase b, whichconverts it into phosphorylase a, that is a more active form.This promotes the glycogenolysis<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Active Glycogen synthase, i.e. dephosphorylated glycogen synthase, is converted back in to inactive phosphorylated glycogen synthase by the process of phosphorylation. It is catalyzed by enzyme <strong>Protein kinase A<\/strong>.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-446\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232.png\" alt=\"\" width=\"319\" height=\"444\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232.png 319w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232-216x300.png 216w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232-65x90.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-232-225x313.png 225w\" sizes=\"auto, (max-width: 319px) 100vw, 319px\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-447\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233.png\" alt=\"\" width=\"601\" height=\"327\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233.png 601w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233-300x163.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233-65x35.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233-225x122.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-233-350x190.png 350w\" sizes=\"auto, (max-width: 601px) 100vw, 601px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<table>\n<tbody>\n<tr>\n<td><strong>you can view video on Regulation of glycogen synthesis<\/strong><\/td>\n<td><a href=\"https:\/\/youtu.be\/fCXkcTWaVkg\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-120\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"\" width=\"36\" height=\"36\" \/><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<div class=\"textbox learning-objectives\">\n<h3>References<\/h3>\n<ul>\n<li style=\"text-align: justify\">Peter J. Roach, Anna A. Depaoli-Roach, Thomas D. Hurley, Vincent S. Tagliabracci (2012) Glycogen and its metabolism: some new developments and old themes. Biochemical Journal, 441 (3) 763-787; DOI: 10.1042\/BJ20111416<\/li>\n<li style=\"text-align: justify\">Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS (2012) Glycogen and its metabolism: some new developments and old themes. Biochem J 441: 763\u2013787. doi: 10.1042\/BJ20111416<\/li>\n<li style=\"text-align: justify\">Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, et al. Regulation of glycogen metabolism in yeast and bacteria. Fems Microbiol Rev. 2010;34(6):952\u2013985.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Web site<\/strong><\/p>\n<ul>\n<li><a href=\"http:\/\/www.wiley.com\/college\/fob\/quiz\/quiz15\/15-20.swf\">http:\/\/www.wiley.com\/college\/fob\/quiz\/quiz15\/15-20.swf<\/a><\/li>\n<li><a href=\"https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/Glycogen%20Metabolism.pdf\">https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/Glycogen%20Metabolism.pdf<\/a><\/li>\n<li><a href=\"http:\/\/themedicalbiochemistrypage.org\/glycogen.php\">http:\/\/themedicalbiochemistrypage.org\/glycogen.php<\/a><\/li>\n<li><a href=\"https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Glycogenesis\">https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Gly<\/a> <a href=\"https:\/\/en.wikibooks.org\/wiki\/Principles_of_Biochemistry\/Gluconeogenesis_and_Glycogenesis\">cogenesis<\/a><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Books<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">Harper\u2019sIllustrated Biochemistry by Robert K.. Murray, Daryl K. Granner, Peter A. Mayes, 26th Edition (2003)<\/li>\n<li style=\"text-align: justify\">Lehninger\u2019S Principle of Biochemistry David L. Nelson and Michael M. Cox,5th Edition (2008)<\/li>\n<li style=\"text-align: justify\">Instant Notes: Biochemistry, 2nd Edition, B.D. Hames &amp; N. M. Hooper (2005)<\/li>\n<li style=\"text-align: justify\">Textbook of Biochemistry, 4th Edition Donald Voet, Judith G. Voet (2011)<\/li>\n<\/ul>\n<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"author":3,"menu_order":27,"template":"","meta":{"_acf_changed":false,"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["dr-chirantan-rawal"],"pb_section_license":""},"chapter-type":[],"contributor":[62],"license":[],"class_list":["post-438","chapter","type-chapter","status-publish","hentry","contributor-dr-chirantan-rawal"],"part":3,"_links":{"self":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/users\/3"}],"version-history":[{"count":5,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/438\/revisions"}],"predecessor-version":[{"id":450,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/438\/revisions\/450"}],"part":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/438\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/media?parent=438"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapter-type?post=438"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/contributor?post=438"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/license?post=438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}