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. A)glucose, lactate, pyruvate B)Pyruvate, lactate, glucose C)Lactate, glucose, pyruvate D)Pyruvate, glucose, lactate E)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 A)To allow for reciprocal regulation of the pathways B)To make each pathway energetically downhill C)So that glucose can be simultaneously made and used in the same cell D)To catalyze reactions unique to each pathway 5. The major purpose of the PPP is _____________, and the secondary purpose is __________. A)NADPH production; regeneration of C6 carbohydrates. B)NAD+ recycling; formation of C5 carbohydrates. C)Synthesis of NADPH; synthesis of C5 carbohydrates D)Synthesis of C5 carbohydrates; synthesis of reducing power E)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 – CO 2 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. Key Regulation At the committed step Principle of Reciprocal regulation Local regulation Hormone regulation

13. Key Regulation Local regulation – AMP/ATP (energy charge) – Citrate (feedback) Hormone regulation – Fructose-2,6-bisphosphate Glucagon signals destruction Gluconeogenesis is stimulated Glycolysis is inhibited

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 1.B 2.E 3.D 4.C 5.C