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Glycogen metabolism.

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Presentation on theme: "Glycogen metabolism."— Presentation transcript:

1 Glycogen metabolism

2 Section of glycogen showing α-1,4- and α-1,6-glycosidic linkages
Glycogen is the major storage of carbohydrate in animals. Glycogen is a branched polymer of α-D- glucose residues linked by α-(1,4)- and α-(1,6)-glycosidic bonds. Section of glycogen showing α-1,4- and α-1,6-glycosidic linkages

3 Glycogenine

4 Glycogenesis Glycogenesis is the synthesis of glycogen from glucose.
It occurs mainly in liver and muscle. Although the liver content of glycogen is greater than that of muscle. Muscle glycogen provides a readily available source of glucose for glycolysis within the muscle. Liver glycogen functions to store and export glucose to maintain blood glucose. However, muscle glycogen is not generally available to other tissues, because muscle lacks the enzyme glucose-6-phosphatase.

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6 Activation of glucose Steps of glycogenesis Activation of glucose.
Initiation . Elongation . Glycogen branching. Activation of glucose Synthesis of glycogen from glucose is carried out by the enzyme glycogen synthase. This enzyme utilizes UDP-glucose as one substrate and the non-reducing end of glycogen as another. UDP-glucose ,the glucose donor in the biosynthesis of glycogen ,is an activated form of glucose

7 ACTIVATION OF GLUCOSE Glucose is phosphorylated to glucose 6- phosphate catalyzed by hexokinase in muscle and glucokinase in liver. glucose 6- phosphate is isomerized to glucose 1- phosphate by phosphoglucomutase. Glucose 1- phosphate react with uridine triphosphate (UTP) to form the active nucleotide uridine Diphosphate glucose ( UDPGLc) and pyrophosphate .This reaction is catalyzed by UDPGLc pyrophosphorylase .

8 Initiation Glycogen synthase can add glycosyl residue only if the polysaccharide chain contain more than four residue. Thus glycogen synthesis require a primer . This primring function is carried out by a protein known as glycogenin that is glycosylated on a specific tyrosine residue by UDPGLs .Further glucose residues are attached in the 1→4 position(catalyzed by glycogenin itself) to form a short chain that is substrate for glycogen synthesis .

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10 Elongation New glucosyl unit are add to the non reducing of glycogen. terminal residue The activated glucosyl unit of UDP glucose is transferred to the hydroxyle group at a C-4 terminus of glycogen to form an α-1,4 –glycosidic linkage. This reaction is catalyzed by glycogen synthase , the key regulator enzyme in glycogen synthesis.

11 Glycogen branching. Glycogen synthase catalyzes only the synthesis of α-1,4 linkages. The α-1,6 branches in glucogyne are produced by the branching enzyme. When the chain is at least 11 glucose residues long branching enzyme transfers a terminal fragment of at least 6-7 glucose residues to an internal glucose residue at the C-6 hydroxyl position to form 1→6linkage (a branch point). In addition ,the new branch point must be at least 4 residue away from a preexisting one

12 Glycogenolysis Glycogenolysis : Degradation of stored glycogen, termed glycogenolysis Different pathways of glycogen breakdown - In muscle: Glycogen → glucose-6-phosphate (G6P) → glycolysis - In liver: Glycogen → G6P → glucose → bloodstream → various cells → glycolysis Because the muscle cells mainly consume glucose molecules whereas the liver cells mainly store the glucose molecules. Glycogen degradation consists of three steps: The release of glucose 1- phosphate from glycogen. The remodeling of the glycogen substrate to permit further degradation The conversion of glucose 1- P to glucose 6-P.

13 Glycogen breakdown requires three enzymes
Glycogen phosphorylase (simply call it phosphorylase) the key enzyme glycogen breakdown, cleaves its substrate and the addition of orthophosphate to yield glucose 1-P. The cleavage of bond by the addition of orthophosphate is referred to as phosphorolysis. (Glycogen)n + Pi ↔ (glycogen)n-1 + G1P (n residues) (n-1 residues) This enzyme releases a glucose unit one by one until it reaches ~ five units (limit branch) from a branch point.

14 2. Transferase and debranching enzyme
Removes branches so that glycogen phosphorylase can complete reaction. The Transferase shift a block of three glucose units from the outer branch and reattached to the non-reducing end of the main chain. The branch point, the glucose attached to the main chain by the α(1-6) glycosidic bond is hydrolyzed by the debranching enzyme ,resulting the release of free glucose molecule.

15 3. Phosphoglucomutase - G1P produced from the glycogen breakdown must be convert to G6P in order to enter glycolysis or to produce glucose in liver. - Phosphoglucomutase catalyzes the conversion of G1P to G6P.

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