Dr. Roger Miesfeld Bioc 460 Spring 20051Carbohydrate Metabolism1. What are the two key regulated enzymes required for glycogen synthesis and glycogenbreakdown? Briefly describe the mechanism(s) that control their activity.2. Individuals with von Gierke's disease, which is a lack of glucose-6-phosphatase in the liver,accumulate large amounts of glycogen in the liver. Why?3. Why would individuals with von Gierke's disease release a small amount of glucose into theblood after injection with a high dose of glucagon?4. Gluconeogenesis and glycolysis are opposing pathways. In what way(s) are they similar andin what way(s) are they different?5. Gluconeogenesis synthesizes glucose from pyruvate, and glycolysis converts glucose intopyruvate. Give a specific example illustrating how allosteric control modulates these twopathways to prevent futile cycling in liver cells.6. Lectins are proteins that bind carbohydrates. What is the name given to the class of proteinson the outermembrane of egg cells that interact with lectin?7. Name the glycolytic enzyme that opposes the reaction in gluconeogenesis catalyzed byfructose 1,6-bisphosphatase? Does AMP activate (+) or inhibit (-) this glycolytic enzyme?8. Why do glucose molecules produced by the glycogen phosphorylase reaction yield more ATPthan dietary glucose? How many more ATPs?9. What is the metabolic logic of differential control of muscle and liver glycogen phosphorylaseby glucose and AMP?10. What is the effect of glucocorticoids on phosphoenolypyruvate carboxykinase in liver cells,and how does this modulate blood glucose levels?11. What carbohydrate molecule is common to both the glycogen phosphorylase and glycogensynthetase reactions?12. What effect does protein kinase A (PKA) activation have on glycogen metabolism withrespect to glycogen synthase and glycogen phosphorylase activities? Does PKA activationincrease or decrease the amount of stored glycogen in the body?13. How many ATPs are produced per mole of glucose by aerobic metabolism in muscle cells ifthe glucose is derived from dietary sources versus glucose produced by glycogenphosphorolysis? Explain.14. A continual supply of reduced glutathione is required to protect red blood cells against thetoxic effects of pamaquine. Why would individuals with a defect in the enzyme glucose 6-phosphate dehydrogenase be susceptible to pamaquine-induced hemolytic anemia?Dr. Roger Miesfeld Bioc 460 Spring 2005215. What explains the observation that people born with a deficiency in the enzyme glucose 6-phosphate dehydrogenase become clinically anemic if they have a diet rich in fava beans?Answers1. Glycogen synthase is the major enzyme required for glycogen synthesis. It is inhibited byphosphorylation. Glucagon, a hormone that signals low glucose levels, stimulatesphosphorylation of glycogen synthase, and also promotes inactivation (by phosphorylation) of aprotein phosphatase inhibitor, thus ensuring that glycogen synthase remains phosphorylatedand inactive. Glycogen phosphorylase is the major enzyme required for glycogen breakdownand it is activated by glucagon through a phosphorylation regulatory mechanism.2. Glucose-6-P accumulates as a result of stimulated glycogen breakdown (glucagon signalslow blood sugar), but because it can't leave the liver, Glu-6-P stimulates glycogen synthase.Moreover, Glu-6-P derived from gluconeogenesis (also stimulated by low blood sugar) isconverted to glycogen by the same mechanism (simulation of glycogen synthase).3. Glucagon stimulates glycogen breakdown, and the product of debranching enzyme is freeglucose, which is released into the blood (~10% of available glucose in glycogen is contained inalpha-1,6 branch points).4. Similarities - both involve many of the same carbohydrate intermediates. - they share some of the same enzymatic reactions. - both are regulated by many of the same effector molecules.Differences - gluconeogenesis is primarily a liver pathway, glycolysis is in every cell. - gluconeogenesis requires ATP, glycolysis generates ATP. - regulatory effectors have opposite effects on these two pathways.5. Phosphofructokinase is activated by F-2,6-BP (AMP) and inhibited by citrate, whereas,Fructose 1,6-bisphosphatase is inhibited by F-2,6-BP (AMP) and activated by citrate.6. Lectins bind to oligosaccharides that are covalently attached to glycoproteins.7. Phosphofructokinase is the glycolytic enzyme that opposes the gluconeogenic enzymefructose 1,6-bisphosphatase, these enzymes interconvert fructose 6-P and fructose 1,6-BP.AMP activates phosphofructokinase.8. The product of the glycogen phosphorylase reaction is glucose-1-phosphate which isisomerized to glucose-6-phosphate and metabolized by the glycolytic pathway. Since thisbypasses the requirement for ATP hydrolysis (by hexokinase) in the first step of the pathway, 1additional ATP is produced by a glycogen derived glucose unit (31 ATPs rather than 30 ATPs).9. Muscle phosphorylase is activated by AMP which would signal a low energy state in the cell.Glucose inhibits liver phosphorylase by feedback inhibition signaling that glucose is not beingexported at a high enough rate to require more glycogen degradation. Muscle phosphorylase isnot inhibited by glucose since muscle cells use glucose for energy production. Degradation ofglycogen in the liver for the purpose of glucose export is independent of the energy needs of theliver cell.Dr. Roger Miesfeld Bioc 460 Spring 2005310. Glucocorticoids induce the expression of the PEPCK gene leading to an increase in thelevels of PEPCK protein in the cell. PEPCK is a key gluconeogenic enzyme and thereforeincreased PEPCK gene expression leads to an increase in glucose production and export fromliver cells via the gluconeogenic pathway.11. Glucose 1-phosphate is one of the products of the phosphorylase reaction and also asubstrate in the glycogen synthase reaction.12. Protein kinase A activation results in the phosphorylation and inactivation of glycogensynthase , and at the same time, the phosphorylation and activation of glycogen phosphorylasethrough the phosphorylation and activation of phosphorylase kinase. PKA activation results indecreased amounts of stored glycogen because glycogen synthase is inactivated and glycogenphosphorylase is activated.13. Dietary glucose must be phosphorylated by hexokinase to produce glucose-6-phosphate, asubstrate in glycolysis. This reaction requires an investment of 1 ATP. The total yield of ATPfrom dietary
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