Gluconeogenesis Exercise
1. The Cori cycle involves glycolysis in skeletal muscle which produces lactate. Lactate is then transported to the liver and converted back to glucose by gluconeogenesis. (This is part of recovery from exercise.)
(a) What is the energy yield per glucose in skeletal muscle?
(b) What is the energy cost per glucose in the liver? (Include lactate → pyruvate)
2. What enzymes are required in gluconeogenesis in order to effectively reverse the irreversible reactions of glycolysis? For each, indicate which glycolytic reaction is being reversed and the energy cost, if any. Classify each of the enzymes.
3. Write the 3-step reaction catalyzed by pyruvate carboxylase. Include biotin in the reaction.
4. Compare and contrast pyruvate decarboxylase and pyruvate carboxylase.
5. Compare and contrast PEP carboxykinase and pyruvate kinase.
6. How can the reactions catalyzed by PFK-1 and FBPase-1 both be favorable?
Key to Gluconeogenesis Exercise
1. (a) 2 ATP per glucose
(b) 4 ATP + 2 GTP per glucose; the 2 NADH required in gluconeogenesis are generated by converting 2 lactate to 2 pyruvate.
2.
Table for Question 2 |
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gluconeogenesis enzymes |
corresponding glycolysis enzymes |
energy cost per pyruvate |
class of enzyme |
pyruvate carboxylase |
pyruvate kinase |
1 ATP |
ligase |
PEP carboxykinase |
pyruvate kinase |
1 GTP |
transferase |
FBPase-1 |
PFK-1 |
none |
hydrolase |
glucose-6-phosphatase |
hexokinase |
none |
hydrolase |
3. a. ATP + HCO3− → ADP + carboxy-P
b. carboxy–P + biotin–E → carboxy–biotin–E + Pi
c. carboxy–biotin–E + pyruvate → oxaloacetate + biotin–E
E = enzyme
4.
Table for Question 4 |
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characteristic |
pyruvate decarboxylase |
pyruvate carboxylase |
Substrate |
pyruvate |
pyruvate |
Does it use a prosthetic coenzyme? |
yes |
yes |
Does it change the number of carbons in pyruvate? |
yes |
yes |
Product |
acetaldehyde |
oxaloacetate |
Does it use a co-substrate coenzyme? |
no |
yes – ATP |
What prosthetic coenzyme does it use? |
TPP |
biotin |
5.
Table for Question 5 |
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characteristic |
PEP carboxykinase |
pyruvate kinase |
Type of enzyme |
transferase |
transferase |
Does it catalyze an irreversible reaction? |
yes |
yes |
Substrate |
oxaloacetate |
PEP |
Product |
PEP (+ CO2) |
pyruvate |
Co-substrate coenzyme |
GTP |
ADP |
6. In both reactions a phosphoryl group is removed, which is energetically favorable. PFK-1 transfers a phosphoryl group from ATP (removing it) to fructose-6-P.
FBPase-1 removes a phosphoryl group from fructose-1,6-bis-phosphate by hydrolyzing the phosphate ester bond.