chapter15 - CHAPTER 15 - GLYCOGEN METABOLISM AND...

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Glucose Glucose 6-phosphate Fructose 6-phosphate Glyceraldehyde 3-phosphate Pyruvate Glycogen (glucose) n Ribose 5-phosphate CHAPTER 15 - GLYCOGEN METABOLISM AND GLUCONEOGENESIS Introduction Certain tissues, such as the brain and red blood cells, rely on glucose for fuel. Serum glucose levels must be maintained at about 5 mM. Serum glucose is maintained by dietary sources, glycogen breakdown, and synthesis from noncarbohydrate precursors via gluconeogenesis (see Figure 1). Glucose is polymerized to glycogen (animal starch) to avoid osmotic imbalances and stored primarily in the muscle and liver. Muscle tissue maintains a store of glycogen for its own use. The liver stores glycogen stores glycogen and breaks it down to glucose for export to other tissues. Notice in the scheme below that glycogen metabolism intersects glycolysis at glucose-6-phosphate. Keep in mind that, since glycogen is stored in a muscle cell for use only in that cell, glucose-6-phosphate is never hydrolyzed to glucose in muscle cells since once glucose is formed it can leave the cell (glucose-6-phosphate cannot leave the cell). Glycogen breakdown can be thought of as a mini-pathway that intersects glycolysis at glucose-6- phosphate. As is typically the case, there is a complementary, biosynthetic pathway that links the same endpoints. As is also typical, some of the enzymes are utilized by both catabolic and biosynthetic pathways, but at one point at the minimum, different enzymes are employed.
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(Glucose) n (Glucose) n-1 Glucose-1-phosphate Glucose-6-phosphate + Different enzymes Same enzyme (Glucose) n + P i n-1 + Glucose 1-phosphate The importance of glycogen as a storage form of glucose is illustrated by a number of genetic diseases associated with abnormal glycogen metabolism. For example, McArdle’s disease is an inherited disease whose main symptom is muscle cramps on exertion. Although synthesized normally, glycogen breakdown is compromised resulting in inadequate supply to meet ATP needs during exertion. Glycogen breakdown Glycogen consists of glucose residues linked by 1,4 linkages with 1,6 branches every 10 residues or so. (See Figure 2 a). The breakdown of glycogen can be though of as a mini- pathway that intersects glycolysis at glucose-6-phosphate Glycogen is catabolized from the non-reducing end via the action of three enzymes, glycogen phosphorylase, glycogen debranching enzyme.and phosphoglucomutase. Glycogen phosphorylase: This enzyme cleaves only glucose residues attached to glycogen via alpha-1,4-linkages. Lysis of the C 1 -O bond provides sufficient energy to produce glucose-1-phosphate without the expenditure of ATP (Figure 15-4). This makes the storage of carbohydrate as glycogen more energy-efficient since ATP is not required to form glucose-6-phosphate (as is not the case in the case of glucose undergoing glycolysis).
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Structural features: Glycogen phosphorylase is a homodimer. The N-terminal domain contains the site of phosphorlyation (ser-14), the allosteric modulator site and a glycogen binding site. The catalytic site is located at the center of the subunit.
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This note was uploaded on 05/05/2011 for the course BIOL 400 taught by Professor Dr.biology during the Spring '11 term at University of Tennessee.

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chapter15 - CHAPTER 15 - GLYCOGEN METABOLISM AND...

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