Unit 11 Flashcards
What is meant by the term gluconeogenesis? Why is this process important in animals? In what tissues does it mainly occur?
Process of generating glucose from non-carbohydrate precursors. Occurs in animal liver mainly.
Name three non-carbohydrate precursors of glucose.
Lactate, glycerladehyde 3-phosphate, triacylglycerols (triglycerides)
Why does gluconeogenesis require a pathway different than the reversal of glycolysis?
Three steps are irreversible in glycolysis and must be bypassed.
What steps in glycolysis are essentially irreversible?
1) Phosphorylation of glucose to glucose 6-phosphate by hexokinase
2) Phosphorylation of fructose 6-phosphate to give fructose 1,6-bisphosphate by phosphofructokinase
3) dephosphorylation of phosphoenolpyruvate to give pyruvate by pyruvate kinase
What is the balanced equation for the conversion of pyruvate to phosphoenolpyruvate?
Pyruvate + HCO3 + ATP + GTP –> PEP + CO2 + ADP + GDP + Pi
Name the cofactor used by pyruvate carboxylase and describe its function. What is the role of ATP in this reaction?
Biotin.
ATP increases the free energy content of bicarbonate and activates it so it can instead be bound to biotin/the enzyme.
In this series of reactions, pyruvate is first carboxylated to oxaloacetate and then decarboxylated to phosphoenol pyruvate. Why is this series of steps important?
The free energy of the pyruvate must first be increased in order for PEP to be favorably formed.
Carboxylation “activates” the pyruvate.
Discuss two alternate pathways from pyruvate to phosphoenol pyruvate. What is the purpose of the variation in the pathway from pyruvate?
The alternative path uses lactate as the starting precursor. Since the conversion of lactate to pyruvate produces 1 NADH in cytosol, the rest of the rxn occurs in the mitochondria.
Write a balanced equation for the reaction catalyzed by fructose 1,6 bisphosphatase 1 (FBPase 1). Name the type of reaction.
Fructose 1,6-bisphosphate + H2O –> fructose 6-phosphate + Pi
Hydrolysis
Write a balanced equation for the reaction catalyzed by glucose 6-phosphatase. Name the type of reaction.
Glucose 6-phosphate + H2O –> glucose + Pi
Hydrolysis
Account for the 6 ATPs required for gluconeogenesis. Remember that we are dealing with the conversion of two moles of pyruvate and that, energetically, ATP and GTP are equivalent.
Per pyruvate: 3 ATP (aka 2 ATP and 1 GTP) and 1 NADH
1 ATP to convert pyruvate to oxaloacetate
1 GTP to convert oxaloacetate to PEP
1 ATP to convert 3 phosphoglycerate to 1,3-bisphosphoglycerate
1 NADH to reduce 1,3-bisphosphoglycerate to glyceraldehyde 3 phosphate
Which other step in gluconeogenesis can be described as an energy input?
Reduction of 1,3-bisphosphoglycerate to glyceraldehyde 3 phosphate. Requires 1 NADH per pyruvate.
What is meant by a “futile cycle”? How are such cycles prevented?
A cycle where two opposing reactions, if allowed to continue in equal and opposite amounts, would consume chemical energy and dissipate it as heat energy without doing any useful metabolic work.
Regulation prevents the reactions from occurring in equal amounts.
Discuss the reciprocal regulation of phosphofructokinase 1 (glycolysis) and fructose 1,6-bisphosphatase (gluconeogenesis) by AMP.
AMP inhibits FBPase1 activity - slows storage of glucose when glucose is needed for breakdown to generate ATP.
AMP activates PFK1 - break down of glucose is increased to replenish ATP stores.
Discuss the reciprocal regulation of PFK1 and FBPase-1 by fructose 2,6-bisphosphate.
Fructose 2,6-bisphosphate inhibits FBPase-1 and activates PFK-1. Overall effect increases ATP production and increases circulating blood glucose by limiting uptake for storage.
