Glycogen Synthesis Biochem 4511 Glycogen is Assembled from Glucose 1 Phosphate Glucose 6 phosphate is converted to glucose 1 phosphate by phosphoglucomutase Glycogen Synthesis Requires Energy Glucose 1 phosphate is further activated by reacting with UTP to yield UDP glucose and pyrophosphate Hydrolysis of inorganic pyrophosphatase is very exergonic and drives the reaction Glycogen Synthesis UDP glucose is combined with the extending glycogen molecule by glycogen synthase Glycogenolysis Glycogen breakdown occurs via different reactions Linear chains are broken down via phosphorolysis Branched chains of glycogen are broken down by hydrolysis Glucose 6 phosphate can enter glycolysis at Step 2 One less ATP is consumed compared to glucose from the bloodstream increasing the net gain of ATP This compensates for the UTP consumed generating glycogen Gluconeogenesis Biochem 4511 Overview of Gluconeogenesis Gluconeogenesis is the formation of glucose from pyruvate glycolysis or oxaloacetate TCA cycle Glycolysis enzymes which catalyze reversible reactions are used Four new enzymes are required Pyruvate carboxylase Phosphoenolpyruvate carboxykinase Fructose bisphosphatase Glucose 6 phosphatase Pyruvate is Converted to PEP in Two Steps The conversion from pyruvate to PEP is an endergonic reaction and is coupled with the hydrolysis of both ATP and GTP CO2 is added in the first step and released in the second Pyruvate Carboxylase Mechanism The pyruvate carboxylase mechanism requires a biotin co factor Many CO2 transfer reactions proceed through a similar mechanism and require biotin The Final Two Unique Enzymes of Gluconeogenesis are Phosphatases Glycolysis and Gluconeogenesis are Opposing Pathways If glycolysis and gluconeogenesis occurred simultaneously there would be a net consumption of ATP For the purposes of balancing energy we can consider GTP to be equivalent to ATP Instead glycolysis and gluconeogenesis are regulated based on the cell s needs Gluconeogenesis is Regulated at the Fructose Bisphosphatase Step Fructose 2 6 bisphosphate regulates both pathways as described and serves as a switch to ensure that the two pathways do not occur simultaneously The Glycolysis Gluconeogenesis Switch Glucose Levels in the Body are Maintained by Gluconeogenesis Remember your brain requires glucose as it lacks enzymes responsible for gluconeogenesis Glucose must be synthesized in the liver and other tissues and transported to the brain through the blood Glucose Regulation and Cellular Signals Epinephrine leads to the breakdown of glycogen through two pathways to trigger the release of free glucose into the blood Insulin indicates a period of high blood sugar and activates glycogen synthesis and glucose uptake in muscle tissue Glucagon signals low blood sugar activates glycogen breakdown and initiates gluconeogenesis Book Problems Chapter 13 before midterm 3 Book problems 3 5 6 12 15 18 21 34 35 37 45 51 Need to know 1 Reactants products cofactors and enzymes involved in each steps of glycolysis 2 Regulation of the first irreversible steps of glycolysis and glycogen synthesis 3 Regulation of the second irreversible step of glycolysis and gluconeogenesis 2014 John Wiley Sons Inc All rights reserved
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