01.24 - Lee - Glycogen

01.24 - Lee - Glycogen - Overview of Energy Metabolism...

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Glucose Fatty Acids Amino-acids NADH FADH 2 NAD + FAD ADP ATP Acetyl CoA Pyruvate GLYCOGEN CO 2 GYCOLYSIS 2 CO 2 Krebs cycle Amino-acids O 2 H 2 O G6P GLUCONEOGENESIS G1-P oxaloacetate Overview of Energy Metabolism •Review the structure of glycogen •Role of glycogen as a storage form of glucose •Breakdown and synthesis of glycogen •Regulation of the enzymes of glycogen metabolism •Genetic diseases of glycogen metabolism –Glycogen storage diseases. 1 Glycogen: Overview of general properties and functions •Storage form of glucose in animal cells. •Major tissues for storage –muscle (0.7%) and liver (4%) •Liver glycogen is important for maintaining glucose levels during fasting (i.e. while sleeping) •Muscle glycogen provides the energy source for strenuous activity (e.g. sprinting). 2 Liver (and to a lesser extent, the Kidney) •Maintains blood glucose at 4-6 mM. •Liver is freely permeable to glucose (via glucose transporters). •There are two sources of glucose that are used by the liver for regulating blood glucose. •Liver stores glucose as glycogen. •Liver is able to synthesize glucose from pyruvate and release it to the bloodstream as glucose. 3
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•The body uses about 200 gm (~7 oz) of glucose a day. •The brain and blood cells are dependent on glucose and account for about 80% of the usage of glucose. •1 teaspoon of sugar ~ 4 grams Liver glycogen 4% 72 grams Muscle Glycogen 0.7% 245 grams Blood glucose 0.1% 10 grams How much is in body tissue: Storage of carbohydrate in postabsortive normal adult human (70 kg). 4 II.Glycogen Structure (pg. 111) •Glycogen consists of linear chains of α-1,4 linked glucose units that are joined by α-1,6 linkages to form a branched macromolecule. 5 •Glycogen is made up of many linear chains of α-1,4-linked glucose units. •These are joined by α -1,6 linkages to form a tree-like structure. •The average chain length for glycogen is 10-12 glucose units per chain for mammalian glycogens. •MW - 10 million [3,000 chains]. α -1,6 linkage Reducing end Non-Reducing end II.Glycogen Structure (pg. 111) 6
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II.Glycogen Structure (pg. 111) •Glycogen is present in granules within cells. •When isolated under mild conditions, is highly particulate. •Under exposure to heat or other treatments, it is water soluble. 7 Glycogen is broken down by phosphorylase in a reaction in which glucose units are removed from the ends of the chains to yield glucose 1-phosphate. The reaction is a phosphorolytic cleavage of the glucosidic bond. The reaction is freely reversible. At equilibrium the ratio of Pi:G1P is about 1:4. III.Glycogen Breakdown (pg. 112) Glycogen (n residues) + Pi Glycogen (n-1 residues) + G-1P 8 III.Glycogen Breakdown (pg. 112) Mobilization of glycogen for energy via glycolysis. In muscle and most tissues, glucose 1-phosphate enters the glycolytic pathway via its conversion to glucose 6-phosphate by
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01.24 - Lee - Glycogen - Overview of Energy Metabolism...

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