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Gluconeogenesis and PPP

Gluconeogenesis and PPP. C483 Spring 2013. 1. An intermediate found in gluconeogenesis and not glycolysis is A) 2-phosphoglycerate. B) oxaloacetate. C) phosphoenolpyruvate . D) fructose 1,6-bisphosphate.

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Gluconeogenesis and PPP

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  1. Gluconeogenesis and PPP C483 Spring 2013

  2. 1. An intermediate found in gluconeogenesis and not glycolysis is A) 2-phosphoglycerate. B) oxaloacetate. C) phosphoenolpyruvate. D) fructose 1,6-bisphosphate. 2. In the Cori Cycle, _____ is transported through blood to the liver, where it is made into ________ and then ___________ for transport out of the liver. glucose, lactate, pyruvate Pyruvate, lactate, glucose Lactate, glucose, pyruvate Pyruvate, glucose, lactate Lactate, pyruvate, glucose 3. Gluconeogenesis is regulated by A) glucagon. B) allosteric modulation. C) concentration of its substrates. D) All of the above.

  3. 4. Which statement is false: The three points of difference between glycolysis and gluconeogenesis are necessary To allow for reciprocal regulation of the pathways To make each pathway energetically downhill So that glucose can be simultaneously made and used in the same cell To catalyze reactions unique to each pathway 5. The major purpose of the PPP is _____________, and the secondary purpose is __________. NADPH production; regeneration of C6 carbohydrates. NAD+ recycling; formation of C5 carbohydrates. Synthesis of NADPH; synthesis of C5 carbohydrates Synthesis of C5 carbohydrates; synthesis of reducing power Oxidative stage; non-oxidative stage

  4. Glucose Metabolism Overview • Keep the main pathway purposes distinct • But learn details of chemistry and regulation based on similarities

  5. Precursors for Gluconeogenesis • Names of compounds? • Type of reaction? • Type of enzyme? • Cofactor(s)? • More on lactate processing…

  6. Cori Cycle • Inter-tissue metabolism • Don’t waste the lactate made in muscle! • Transport to live • Convert to pyruvate then glucose • Store glucose • Which can be sent back to muscle

  7. Chemistry of Gluconeogenesis • Chemically opposite of glycolysis (mainly) • Energetically costly—no perpetual motion machine! • Points of regulation

  8. Glycolysis • Step 1: costs 1 ATP • Step 3: costs 1 ATP • Step 7: makes 2 ATP • Step 10: makes 2 ATP • Gluconeogenesis • Step 10: no change • Step 8: no change • Step 3: costs 2 ATP • Step 1: costs 4 ATP equivalents

  9. Step 1 • Pyruvate Carboxylase • Biotin • ATP cost to make driving force for next reaction • PEP carboxykinase • ATP cost to restore PEP • CO2 loss drives rxn

  10. Step 8 • Fructose-1,6-bisphosphatase • No additional energy input • Phosphate ester hydrolysis is spontaneous

  11. Step 10 • Glucose 6-phosphatase • Liver (and others) • Not in muscle

  12. Regulation • Principle of Reciprocal regulation • AMP • Citrate/Acetyl CoA • Frutose-2,6-bisphosphate

  13. Key Regulation • Reciprical Regulation of PFK-1 and fructose-1,6-bisphosphatase • Energy waste at committed step • Hormone regulated

  14. Glucose Metabolism Overview • Gluconeogenesis • Pentose Phosphate Pathway • Glycogen metabolism

  15. Pentose Phosphate Pathway • Dual Purpose • Synthesis of “reducing potential” • Synthesis of 5-carbon sugars • Net reaction

  16. Complex, 2-Stage Process • No details except glucose-6-P DH • No reactions! • Just overall purposes • Oxidative Stage • Non-oxidative stage

  17. Non-oxidative Stage • To understand purpose, realize that we generally need to make much more NADPH than ribose • Problem: stuck with C5, but need C6 and C3 • Solution: “Shunt” C5 back to C6 through near-equilibrium reactions

  18. Answers • B • E • D • C • C

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