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Lecture 16

Lecture 16: "Carbohydrate Metabolism"

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Biochemistry 2280A
Mel Usselman

Biochemistry Lecture No. 16: Carbohydrate Metabolism Tuesday October 16 , 2012 Overview Of Carbohydrate Metabolism: -Carbohydrate metabolism encompasses 4 key bodily actions: Glycogen synthesis and breakdown, glycolysis and fermentation, gluconeogenesis, and the pentose phosphate pathway. Carbohydrate Storage As Glycogen: -In the process of carbohydrate storage as glycogen, glycogen synthase catalyzes the conversion of glucose-1-phosphate to glycogen using UTP (ATP equivalent) as an energy source, while glycogen phosphorylase catalyzes the breakdown of glycogen to glucose-1-phosphate by way of phosphorylation (P). As coupled UTP hydrolysis is required to convert glucose-1-phosphate into glycogen, it is unlikely i that glycogen synthase will convert glycogen into glucose-1-phosphate. -An equilibrium between glucose-6-phosphate and glucose-1-phosphate is also established (they are energetically neutral to each other). There is no equilibrium between glycogen and glucose-1-phosphate because two different enzymes are utilized in catalysis. Allosteric Regulation In Skeletal Muscle: -In skeletal muscle cells, glucose-6-phosphate allosterically activates glycogen synthase, while AMP activates glycogen phosphorylase. ATP and glucose-6-phosphate are both inhibitors of glycogen phosphorylase. Allosteric Regulation In Liver: -The liver has isozymes, enabling it to respond to regulation in a slightly different manner than the muscles do (neither ATP nor AMP regulate/inhibit glycogen phosphorylase activity in the liver). Glucose is an allosteric inhibitor of glycogen phosphorylase (high blood sugar), while glucose-6-phosphate allosterically activates glycogen synthase (same as in the muscles). Control By Phosphorylation In Liver & Muscle: -Insulin leads to the dephosphorylation of both enzymes in the liver and muscles (activates glycogen synthase and deactivates glycogen phosphorylase). Glucagon leads to phosphorylation in the liver only because the muscles are insensitive to glucagon, while the liver attempts to keep blood glucose levels constant. Epinephrine leads to phosphorylation in the liver and muscles (activates glycogen phosphorylase and deactivates glycogen synthase). -Let it be noted also that the preferred energy source of the brain is glucose, which is why the liver releases glucose to stimulate brain comprehension in times of stress (use of epinephrine). Net Reaction & ΔG Values For Glycolysis: -The whole point of glycolysis is to make ATP and any monosaccharide can be incorporated and converted in this pathway. The pyruvate from glycolysis would then be oxidized in the mitochondria, the ATP is stored for useable energy, and the NADH head off to the electron transport chain in the mitochondria. Steps 1, 3 and 10 (irreversible reactions) are targets for control of flux through glycolysis. Control Of Flux Through Glycolysis: -Citrate inhibits the pathway at step 3 by inactivating phosphofructokinase. Insulin also regulates glycolysis among other things as high insulin level increases the amount of fructose-2, 6-bisphosphate, which activates phosphofructokinase and allows the glycolysis pathway to proceed. High ATP concentration is also recognized as inhibiting glycolysis at step 3, while high concentrations of AMP, ADP or Piactivate glycolysis at step 3. Strategies For Fermentation: -Fermentation is a process that regenerates NAD (in order to convert glucose to pyruvate) and allows + + ATP synthesis via gly
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