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

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Gluconeogenesis and PPP C483 Spring 2013 Slide 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. Slide 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 Slide 4 Glucose Metabolism Overview Keep the main pathway purposes distinct But learn details of chemistry and regulation based on similarities Slide 5 Precursors for Gluconeogenesis Names of compounds? Type of reaction? Type of enzyme? Cofactor(s)? More on lactate processing Slide 6 Cori Cycle Inter-tissue metabolism Dont waste the lactate made in muscle! Transport to live Convert to pyruvate then glucose Store glucose Which can be sent back to muscle Slide 7 Chemistry of Gluconeogenesis Chemically opposite of glycolysis (mainly) Energetically costlyno perpetual motion machine! Points of regulation Slide 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 Slide 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 Slide 10 Step 8 Fructose-1,6-bisphosphatase No additional energy input Phosphate ester hydrolysis is spontaneous Slide 11 Step 10 Glucose 6-phosphatase Liver (and others) Not in muscle Slide 12 Key Regulation At the committed step Principle of Reciprocal regulation Local regulation Hormone regulation Slide 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 Slide 14 Glucose Metabolism Overview Gluconeogenesis Pentose Phosphate Pathway Glycogen metabolism Slide 15 Pentose Phosphate Pathway Dual Purpose Synthesis of reducing potential Synthesis of 5-carbon sugars Net reaction Slide 16 Complex, 2-Stage Process No details except glucose-6-P DH No reactions! Just overall purposes Oxidative Stage Non-oxidative stage Slide 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 Slide 18 Answers 1.B 2.E 3.D 4.C 5.C