1. An intermediate found in gluconeogenesis and not glycolysis isA) 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, pyruvateB) Pyruvate, lactate, glucoseC) Lactate, glucose, pyruvateD) Pyruvate, glucose, lactateE) Lactate, pyruvate, glucose
3. Gluconeogenesis is regulated by A) glucagon.B) allosteric modulation.C) concentration of its substrates.D) All of the above.
4. Which statement is false: The three points of difference between glycolysis and gluconeogenesis are necessaryA) To allow for reciprocal regulation of the pathwaysB) To make each pathway energetically downhillC) So that glucose can be simultaneously made and used in the same cellD) To catalyze reactions unique to each pathway
5. The major purpose of the PPP is _____________, and the secondary purpose is __________.E) NADPH production; regeneration of C6 carbohydrates.F) NAD+ recycling; formation of C5 carbohydrates.G) Synthesis of NADPH; synthesis of C5 carbohydratesH) Synthesis of C5 carbohydrates; synthesis of reducing powerI) Oxidative stage; non-oxidative stage
Glucose Metabolism Overview
• Keep the main pathway purposes distinct
• But learn details of chemistry and regulation based on similarities
O
HO
HO
OH (P)
OH
OH
DHAP
Pyruvate
Gluconeogenesis
Lactate
Amino Acids
Glycerol(Triacylglycerides)
Glycogen
Glycogen Degradation
Glycogen
Glycogen Synthesis
Ribose,NADPH
ATP
DHAP
Pyruvate
Pentose Phosphate Pathway
Energy Production
Starch
Diet
Precursors for Gluconeogenesis
• Names of compounds?
• Type of reaction?• Type of enzyme?• Cofactor(s)?• More on lactate
processing…
OH
OH
OH
OPO3
O
OH
O
O
O
NH2
O
O
O
O
O
OH
O
O
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
Chemistry of Gluconeogenesis
• Chemically opposite of glycolysis (mainly)• Energetically costly—no perpetual motion
machine!• Points of regulation
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
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
Step 8• Fructose-1,6-bisphosphatase• No additional energy input• Phosphate ester hydrolysis is spontaneous
Key Regulation• At the committed
step• Principle of
Reciprocal regulation
• Local regulation• Hormone
regulation
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
Glucose Metabolism Overview
• Gluconeogenesis• Pentose
Phosphate Pathway
• Glycogen metabolism
O
HO
HO
OH (P)
OH
OH
DHAP
Pyruvate
Gluconeogenesis
Lactate
Amino Acids
Glycerol(Triacylglycerides)
Glycogen
Glycogen Degradation
Glycogen
Glycogen Synthesis
Ribose,NADPH
ATP
DHAP
Pyruvate
Pentose Phosphate Pathway
Energy Production
Pentose Phosphate Pathway
• Dual Purpose– Synthesis of “reducing potential”– Synthesis of 5-carbon sugars
• Net reaction
Complex, 2-Stage Process
• No details except glucose-6-P DH
• No reactions!• Just overall
purposes– Oxidative Stage– Non-oxidative
stage
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