The concentration of glucose residues stored as glycogen in liver is ~0.4M, Whereas, glycogen concentration is only 10 nm.
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1 The concentration of glucose residues stored as glycogen in liver is ~0.4M, Whereas, glycogen concentration is only 10 nm. IV: Large amount of glucose can be stored without affecting the osmolarity of the cells. So that multiple glycogen phosphorylases can act at several non-reducing ends of glycogen chains to generate large amount of Glucose-1-P for glycolysis, or to release glucose in blood very quickly. 1
2 3. Glycogen Debranching enzyme: Glycogen phosphorylase proceeds along glycogen chain until it approaches close to (about 4-5 residue away) the α (1 6) branch point. Glycogen debranching enzyme takes over from here. This protein has two activities; 1. Acts as an α(1-4) transglycosylase or glycosyltransferase: It transfers an α(1-4)-linked trisaccharide unit from the limit branch to the nonreducing end of another branch. 2. This enzyme also has a separate site for the α(1 6) glucosidase activity, by which it hydrolyses the remaining glucose of the branch liked by a(1 6) link to the main chain releasing free glucose not the G1P. Approximately 10% of the total glucose residues generated from glycogen breakdown are as free glucose and 90% as G1P. 2
3 Glycogen Synthesis: This part will be covered in Metabolism II. However, for the purpose of understanding the regulation of glycogen metabolism it is briefly mentioned below. Glycogen synthesis is achieved by three enzymes I. UDP-glucose phosphorylase II. Glycogen synthase III. Branching enzyme Regulation of Glycogen metabolism: Glycogen is stored in liver and muscle as emergency energy source. Its breakdown during need of energy and it s synthesis to replenish the store is tightly regulated. Glycogen metabolism is regulated both by different metabolites present in the cells as well as by hormones through signal transduction cascades. Activities of the two enzymes of glycogen metabolism are critical for the control of this pathway 1. Glycogen phosphorylase 2. Glycogen synthase The enzymatic activities of Glycogen phosphorylase and glycogen synthase are controlled by two ways; I. By direct allosteric control II. By covalent modification Allosteric control: G6P and ATP are allosteric inhibitors of Glycogen phosphorylase whereasamp is an allosteric acivator. G6P is an allosteric activator of glycogen synthase. Control by phosphorylation: Phosphorylase a (phosphorylated form) is more active than phosphorylase b (dephosphorylated form. Phosphorylase a is insensitive to inhibition by ATP 3
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5 Insulin-stimulated protein kinase Glycogen Storage Diseases: These are inherited disorders which are caused by defects in the genes encoding enzymes involved in synthesis and break down of glycogen. The defects in liver enzymes generally cause hepatomegaly (enlarged liver) and hypoglycemia whereas those in muscle enzymes generally cause muscle cramps. Type I: Glucose 6-Phosphatase deficiency (von Gierke s Disease): This enzyme catalyses step which leads to the delivery of glucose in blood stream from liver. In the absence of this enzyme, liver is unable to release glucose in blood, leading to hypoglycemia. Ther is build up of G6P in the liver which activates glycogen synthase leading to build up of huge glycogen store and hepatomegaly. Treatments include, inhibition of glucose by liver by drugs and, continued intragastric feeding overnight and liver transplantation. Type IV: Branching enzyme deficiency (Anderson s Disease): Presence of unbrached long chains of glycogen, which become insoluble particles, causing sever liver malfunction. The abnormal size particle may trigger immune response that causes liver damage and death of the patients within 4 yr of age. Type 0: Liver glycogen synthase deficiency: This is the only disease of glycogen metabolism where there is deficiency of glycogen. Hyperglycmia after the meals and hypoglycemia in other times. Type V: Muscle phosphorylase deficiency (McArdle s Disease): symptoms appear in adulthood with severe muscle cramps after strenuous exercise. Blood glucose remain unaffected. Type VI: Liver phosphorylase deficiency (Her s Disease): Patients unable to use liver glycogen. Symptoms and treatments are similar to type I disease. 5
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