Glycogen metabolism 1 anscfstc 607 physiology and biochemistry of muscle as a food glycogen metabolism i. The interaction of glycogenin with actin filaments is required to initiate the synthesis of glycogen. Glycogenin is an enzyme involved in converting glucose to glycogen. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. A cartoon representing the secondary structure organizations of atgs shown. Glycogenin undergoes selfglucosylation to generate an oligosaccharide primer, which, when long enough, supports the action of glycogen synthase to elongate the polysaccharide chain, leading ultimately to the formation of glycogen. Glycogen synthesis and degradation homo sapiens wikipathways. It is a homodimer of 37kda subunits and is classified as a glycosyltransferase it catalyzes the chemical reaction. Glycogen is a chain of glucose subunits held together by. Glycogen is a very large, branched polymer of glucose residues. Glycogenin binds to actin filaments therough a domain in the cterminus of the protein.
Energy from excess glucose can be stored as fat or glycogen. Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy. Branching is important because it increases the solubility of glycogen. Allosteric regulation of glycogen synthase controls glycogen. Learn and reinforce your understanding of glycogen metabolism through video.
The amount of stored glycogen is dependent on the abundance of synthesis enzymes 19, and 186 glycogen synthesis in stm is mainly mediated by enzymes glga and glgc 20. Glucose is the principal metabolic fuel for the brain, and the concentration of glucose in circulating blood must be maintained at about 5 mm for this purpose. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two. There is an energetic barrier to the direct incorporation of g1p into glycogen due to concentrations of factors that favor breakdown of glycogen under normal conditions over synthesis of.
Control of glycogen synthesis in cultured human muscle cells. It is a homodimer of 37 kda subunits and is classified as a glycosyltransferase. Glycogen is degraded by the sequential action of three enzymes. Glycogen synthase can add glucosyl residues only if the polysaccharide chain already contains more than four residues. Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. Glycogen biosynthesis involves the action of several enzymes.
Apr 09, 2016 gluconeogenesis from lactate, glycerol, propionyl coa and glucogenic amino acids duration. In myocytes muscle cells, glycogen degradation serves to provide an immediate source of glucose6phosphate for glycolysis, to provide energy for muscle contraction. Pdf glycogen metabolism in muscle and its effects on meat. Glycogen synthesis, breakdown, and storage diseases. Regulation of glycogen synthesis and degradation greek. Carbon 1 of the first unit of this chain, the reducing end, is covalently. Active campdependent protein kinase phosphorylates glycogen phosphorylase kinase often referred to as simply phosphorylase kinase, converting it from the inactive b form to the active a form. This polymer of glucose residues linked by a 1,4 and a 1,6 glycosidic bonds. Glycogen biosynthesis involves the action of several enzymes among which. This phosphorylation leads to the association of the rgl subunit with pp1 and the glycogen molecule. Glycogen synthesis was determined as 14 cglucose incorporation into glycogen.
Glycogen biosynthesis involves a specific initiation event, mediated by a specialized protein, glycogenin. In the liver, glycogen synthesis and degradation are regulated to maintain bloodglucose levels as required to meet the needs of the organism as a whole. Glycogen is synthesized from glucose glycogen degradation produces glucose 1phosphate as the major product, but free glucose is also formed liver glycogen is used to maintain blood glucose during fasting or exercise. It has a similar structure to amylopectin which is a component of starch, more extensively branched and compact than starch. With glycogen breakdown do you mean gluconeogenesis. Both muscle contraction and insulin have been shown to increase the activity of glycogen synthase, the ratelimiting enzyme in glycogen synthesis. Carbohydrate storage and breakdown biology libretexts.
Furthermore, branching creates a large number of terminal residues,the sites of action of glycogen phosphorylase and synthase. Third, given that steadystate levels of glycogen are determined by the balance between synthesis and degradation in vivo, it is possible that glycogenolysis was inhibited as a result of some compensatory mechanism in muscles of gs r582ar582a knockin mice to avoid a profound depletion of glycogen. During glycogen synthesis, g6p is converted to udpglucose and the glucosyl unit from udpglucose is used to elongate a nascent glycogen chain through. This glucosyltransferase is capable of transferring a glucosyl residue from udpglucose to the hydroxyl group of its own tyrosine 194, and adding the subsequent 1,4linked glucose units to form a linear oligosaccharide up to 11 glucosyl residues long. Regulation of glycogen synthase kinasephosphatase activity. This work was supported in part by the basic research program through the.
The enzymes are nested between the outer branches of the glycogen molecules and act on the nonreducing ends. We now return to the regulation of glycogen metabolism with a knowledge of both degradation and synthesis. Degradationoflabeled glycogen wasgreater in the fed versus thefasted rats p synthesis in fed rats wasdueto degradation. Medium was then removed, and the cells were rapidly washed five times in icecold phosphatebuffered saline. I am assuming that you are familiar with the pathways of glycogen synthesis and breakdown. Determinants of postexercise glycogen synthesis during short. In contrast to glycogen degradation, the synthesis is an energy requiring pathway which is distinct from allowing for the reciprocal control of the synthesis and degradation. Cells were incubated for 1 h in culture medium containing u14 cglucose 5. Structure glycogen is a polymer of glucose up to 120,000 glucose residues and is a primary carbohydrate storage form in animals.
Mar 19, 2012 glycogen synthesis and degradation techined. Following this rapid phase of glycogen synthesis, muscle glycogen synthesis occurs at a much slower rate and this phase can last for several hours. The glycogen granules contain both glycogen and the enzymes of glycogen synthesis glycogenesis and degradation glycogenolysis. The steps in the glycogen breakdown regulatory pathway can be reversed at. Glycogen degradation and glycogen synthesis are re. As seen on the illustration, glucose and glucose 6phosphate both allosterically activate glycogen synthase. Glycogen synthesis and degradation glycogen is a form of stored glucose which is relatively inert while being readily mobilised form of glucose. Glycogenolysis takes place in the cells of the muscle and liver tissues in response to hormonal and neural signals. Glycogen synthase, the enzyme transfers the glucose from udpglc to the nonreducing end of glycogen to form alpha 1,4linkages. Glycogen homeostasis involves the concerted regulation of the rate of glycogen synthesis glycogenesis and the rate of glycogen breakdown glycogenolysis. Glycogen synthase cleaves the ester bond between c1 of glucose and the pyrophosphate of udp. Identify the components of this cascade indicated in the questions below. Learn vocabulary, terms, and more with flashcards, games, and other study tools. As you can see, the regular, periodic structure of glycogen corresponds to similarly regular and periodic methods of synthesis and breakdown that require only a small number of different enzymes.
What is the effect of changes in the insulin, blood glucose or epinephrine upon glycogen synthesis or glycogen degradation in muscle. The regulatory molecule in this case is glucagon which achieves the opposite of insulin this initiates the conversion of glucose into glycogen. Increases glycogen synthesis, fatty acidtag biosynthesis and decrease glucose production. It forms a new alpha 1,4glycosidic bond on a glycogen chain that has a minimum of 4 glucose residues. Theses two processes are reciprocally regulated such that hormones that stimulate glycogenolysis e.
Activation of glycogen synthesis by insulin mechanism. In particular, glycogenolysis plays an important role in the fightorflight response and the regulation of glucose levels in the blood in myocytes muscle cells, glycogen degradation serves to provide an immediate source of glucose6phosphate for glycolysis, to. Just as cells reciprocally regulate glycolysis and gluconeogenesis to prevent a futile cycle, so too do cells use reciprocal schemes to regulate glycogen breakdown and synthesis. The consequent dephosphorylation of glycogen synthase, phosphorylase kinase, and phosphorylase promotes glycogen synthesis and blocks its degradation. Glycogen storage diseases gsd are inherited metabolic disorders of glycogen metabolism. The polymer is composed of units of glucose linked alpha14 with branches occurring alpha16 approximately every 812 residues. It uses pyridoxal, a vitamin b 6 derivative, as cofactor. In this video im explaining glycogen synthesis and degradation details in the form of animation slides. Saving for lean times glycogen synthesis dietary intake of glucose or carbohydrates frequently exceeds immediate need.
Glycogenin, the primer of glycogen synthesis, binds to actin. The mechanism of hexose polymerization in starch synthesis is essentially similar to that in glycogen synthesis. The liver is a socalled altruistic organ, which releases glucose into the blood to meet tissue need. Synthetic pathway involves a highenergy intermediate udpglucose, which acts as a glucosyl donor for the synthesis of glycogen. Glucose derived from glycogen breakdown is also a primary. The regulation involves an enzymatic cascade using camp as a secondary messenger. A glycogen storage disease gsd, also glycogenosis and dextrinosis is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis glucose breakdown, typically in muscles andor liver cells. These findings show that glycogen metabolism in macrophages is an. Glycogen is degraded by glycogen phosphorylase and debranching enzyme.
Glycogen is synthesized and degraded by different pathways. Thus,branching increases the rate of glycogen synthesis and degradation. Usmle is a joint program of the federation of state medical boards fsmb and. Starch, like glycogen, is a high molecular weight polymer of dglucose in. Let us first consider the steps in glycogen synthesis. The mechanism of hexose polymerization in starch synthesis is essentially similar to. Glycogen synthase udpglucoseglycogen glucosyltransferase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. In order of their activation, be able to name and give the reason for the activation of all the intermediates in the camp cascade in. Lecture 3 glycogen synthesis biochemistry415\515 glycogen. Synthesis and degradation of glycogen is important to reserve the energy and serve the metabolic needs of the organism.
Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme gsy. Pp1 is therefore the only regulator that directly regulates both gs and glycogen phosphorylase. It is a very large molecule up to 120,000 glucose residues per mole and highly branched polymer of glucose consisting of mainly 1,4 linked glucose residues with 1,6branches every ten residues or so. Glucose released from muscle glycogen stores is used on site to provide energy for muscle contraction. Glycogen degradation produces glucose 1phosphate as the major product, but free glucose is also formed. Glycogen metabolism regulates macrophagemediated acute. Glycogen breakdown and synthesis are reciprocally regulated. This priming function is carried out by glycogenin, a protein composed of two identical 37kd subunits, each bearing an oligosaccharide of. Glycogen synthase and glycogen phosphorylase, which breaks down glycogen, can only work on nonreducing ends. Within skeletal muscle and liver glucose is stored as glycogen. More compact calg, special storage site white adipose, unlimited storage capacity disadvantage. By increasing the number of these ends, the enzymes can work at many ends simultaneously and massively increase the speed of degradation and synthesis. In this step, the formation of branches is brought about by the action. Glycogen synthase catalyzes the synthesis of a linear unbranched molecule with alpha1,4glycosidic linkages.
Glycogenesis is the process of glycogen synthesis glycogen is synthesized when blood glucose levels are. Pp1 is, in turn, activated by factors shown on the illustration to the right. Glycogen breakdown and synthesis are reciprocally regulated by a hormonetriggered camp cascade acting through protein kinase a figure 21. Birth removes the constant source of glucose and the shock of having to breath results in increased epinephrine synthesis and therefore glycogen degradationglucagon signaling also increases with the drop in insulin and glucose further supporting glycogen. It acts as a primer, by polymerizing the first few glucose molecules, after which other enzymes take over. Glycogen synthesis and degradation flashcards quizlet. Its the process whereby glycogen a storage molecule of glucose is converted back into glucose to meet the bodys energy demands.
The ppp can be divided into oxidative and nonoxidative steps. Protein involved in the synthesis of glycogen, a branched polymer of dglucose mostly 14 linked, but with some 16 linked residues at branch points. Glycogen degradation and glycogen synthesis are reciprocally regulated, which prevents a futile cycle of simultaneous degradation and synthesis. Like glycolysis and gluconeogenesis, glycogenolysis and glycogenesis are not. Aug 12, 2012 branching is important because it increases the solubility of glycogen. This slide summarizes the enzyme reactions that occur in glycogen synthesis and degradation, respectively.
Role of glycogenin 1binds glucose residues 2serves as primer for glycogen synthesis. Reciprocal hormonal regulation of glycogen synthesis and degradation. They provide energy quickly through glycolysis and passing of. Glycogen synthase catalyzes the conversion of the glucosyl glc moiety of uridine diphosphate glucose udpglc into glucose to be incorporated into glycogen via an.
The anabolic pathway contrasting with glycogen breakdown is that of glycogen synthesis. A cartoon showing the general fold and secondary structure organization of atgs. Glycogen refers to the analog of starch which is a glucose polymer that functions as energy storage in plants. Allosteric regulation of glycogen synthase controls. Birth removes the constant source of glucose and the shock of having to breath results in increased epinephrine synthesis and therefore glycogen degradation glucagon signaling also increases with the drop in insulin and glucose further supporting glycogen degradation. Mar 09, 2014 glycogen is a chain of glucose subunits held together by. Because of muscle mass, muscle contains three to four times as much glycogen as. Determinants of postexercise glycogen synthesis during. It can only cleave glucose residues 4 or more glucose residues away from a branching point. In particular, glycogenolysis plays an important role in the fightorflight response and the regulation of glucose levels in the blood. Glycogen is the major short term storage polymer of animal cells and is particularly abundant in liver and to a lesser extent in muscles. Decreases glycogen breakdown and tag breakdown lipolysis term.
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