CHAPTER 22: Unit 8. Glycogen Synthesis and Degradation

• Glycogen is a large polymer of glucose residues linked by 1,4-glucosidic bonds with branches every 10 residues or via  1-6 glucosidic bonds. Glycogen provides an important energy reserve for the body.

• Glycogen is stored in virtually all tissues, but mainly muscle and liver
• Is converted to glucose 1-phosphate
• Can be converted to G6P for glycolysis in liver and muscle, or into glucose in the liver
• Is a large molecule composed of up to 50 000 glucose units bound by α1 -> 4 bonds, with α1 -> 6 bonds every 8-12 residues to create branches.
• Has one reducing end and many non-reducing ends
• The reducing end is attached to a protein called glycogenin
• PP1 is a covalent modifier of both glycogen synthase and glycogen phosphorylase

Synthesis

The pathway of synthesis goes as follows: glucose -> G6P -> G1P -> UDP-glucose. The glucose unit of UDP-glucose is then attached to a non-reducing end of glycogen by glycogen synthase.

Glycogen

Glycogen is the storage form of glucose in animals and humans which is analogous to the starch in plants. Glycogen is synthesized and stored mainly in the liver and the muscles. Structurally, glycogen is very similar to amylopectin with alpha acetal linkages, however, it has even more branching and more glucose units are present than in amylopectin. Various samples of glycogen have been measured at 1,700-600,000 units of glucose.The structure of glycogen consists of long polymer chains of glucose units connected by an alpha acetal linkage. The graphic on the left shows a very small portion of a glycogen chain. All of the monomer units are alpha-D-glucose, and all the alpha acetal links connect C # 1 of one glucose to C # 4 of the next glucose.The branches are formed by linking C # 1 to a C # 6 through an acetal linkages. In glycogen, the branches occur at intervals of 8-10 glucose units, while in amylopectin the branches are separated by 12-20 glucose units.

Reference: http://chemistry.elmhurst.edu/vchembook/547glycogen.html

Biosynthesis of GlycogenThe goal of glycolysis, glycogenolysis, and the citric acid cycle is to conserve energy as ATP from the catabolism of carbohydrates. If the cells have sufficient supplies of ATP, then these pathways and cycles are inhibited. Under these conditions of excess ATP, the liver will attempt to convert a variety of excess molecules into glucose and/or glycogen.

GlycogenesisGlycogenesis is the formation of glycogen from glucose. Glycogen is synthesized depending on the demand for glucose and ATP (energy). If both are present in relatively high amounts, then the excess of insulin promotes the glucose conversion into glycogen for storage in liver and muscle cells.In the synthesis of glycogen, one ATP is required per glucose incorporated into the polymeric branched structure of glycogen. actually, glucose-6-phosphate is the cross-roads compound. Glucose-6-phosphate is synthesized directly from glucose or as the end product of gluconeogenesis. Degradation of glycogenGlycogen synthase can only catalyse the creation of α1 -> 4 bonds. For the creation of the branches in the glycogen molecule, glycogen branching enzyme is needed. The advantage of these branches is that the number of non-reducing ends are increased from 1 to many. Glycogen synthase and glycogen phosphorylase, which breaks down glycogen, can only work on non-reducing ends. By increasing the number of these ends, the enzymes can work at many ends simultaneously and massively increase the speed of degradation and synthesis. DegradationGlycogen is degraded by glycogen phosphorylase and debranching enzyme. The former converts the glucose units into glucose 1-phosphate by breaking of α1 -> 4 bonds. Debranching enzymes has two activities, transferase activity and glucosidase activity. When glycogen phosphorylase has reached the last 4 glucose units of a branch, the transferase activity of debranching enzyme takes the outermost 3 glucose units and puts them on the “main chain”, while leaving a branch of just 1 glucose. The glucosidase activity of debranching enzyme converts the last glucose on the branch into glucose 1-phosphate.Glucose 1-phosphate can be converted into G6P, which can be further converted into glucose (in liver and kidney only), or go into the glycolysis.

Reference:
https://www.youtube.com/watch?v=P_5ubq6MikQ

Glycogenosis

Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels.

Glycogenesis, the formation of glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, from glucose. Glycogenesis takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells.

Glycogenesis is stimulated by the hormone insulin. Insulin facilitates the uptake of glucose into muscle cells, though it is not required for the transport of glucose into liver cells. However, insulin has profound effects on glucose metabolism in liver cells, stimulating glycogenesis and inhibiting glycogenolysis, the breakdown of glycogen into glucose. Compare glycogenolysis.

Reference:

GlycogenolysisIn glycogenolysis, glycogen stored in the liver and muscles, is converted first to glucose-1- phosphate and then into glucose-6-phosphate. Two hormones which control glycogenolysis are a peptide, glucagon from the pancreas and epinephrine from the adrenal glands.Glucagon is released from the pancreas in response to low blood glucose and epinephrine is released in response to a threat or stress. Both hormones act upon enzymes to stimulate glycogen phosphorylase to begin glycogenolysis and inhibit glycogen synthetase (to stop glycogenesis).Glycogen is a highly branched polymeric structure containing glucose as the basic monomer. First individual glucose molecules are hydrolyzed from the chain, followed by the addition of a phosphate group at C-1. In the next step the phosphate is moved to the C-6 position to give glucose 6-phosphate, a cross road compound.Glucose-6-phosphate is the first step of the glycolysis pathway if glycogen is the carbohydrate source and further energy is needed. If energy is not immediately needed, the glucose-6-phosphate is converted to glucose for distribution in the blood to various cells such as brain cells.

Reference: http://chemistry.elmhurst.edu/vchembook/604glycogenesis.html

Regulation of Glycogen MetabolismGlycogen metabolism in the liver is subject to complex regulations in which substrates or hormones may interact in different ways according to the nutritional conditions. Activation of glycogen synthesis strongly depends on the availability of glucose, gluconeognic substrates and amino acids. These factors act mainly by a direct or indirect activation of the synthase phosphatase. On the other hand, cAMP or Ca(2+)-dependent glycogenolytic agents cause glycogen degradation by the mean of specific protein kinases which may inactivate the glycogen synthase or activate the glycogen phosphorylase. The active form of glycogen phosphorylase is a potent allosteric inhibitor of the synthase phosphatase. Insulin increases glycogen synthesis by counteracting the action of glycogenolytic hormones and by enhancing the glucose induced activation of glycogen synthase.The brain, skeletal muscles, and red blood cells require large amounts of glucose every day to function properly. To protect the brain, hormones with opposing actions control blood glucose. When glucose is low, glucagon, a hormone produced in the pancreas, is secreted into the bloodstream. Glucagon signals cells in the liver to increase the rate of glycogenolysis, which raises blood glucose levels. At the same time, glucagon inhibits the synthesis of glycogen.Regulation occurs on the enzymes glycogen phosphorylase and glycogen synthase, and involves allosterism, covalent modification of enzymes and, ultimately, hormonal control. Allosteric factors – ATP, G6P, AMP. Glycogen phosphorylase is regulated by both allosteric factors and by covalent modification (phosphorylation).

Reference:
https://www.youtube.com/watch?v=oWp51lQUE_I

Reference:
https://www.youtube.com/watch?v=NL6ETs9k3Wk