Exam 3 - Glycolysis Regulation Flashcards
What reaction product strongly inhibits the function of hexokinase?
Glucose 6-phosphate
Is Hexokinase always operating at Vmax?
Yes
Glucokinase is [] inhibited by glucose 6-phosphate
NOT
Glucokinase activity is regulated by [] of the enzyme between the cytoplasm and the []
- translocation
- nucleus
Glucokinase
- GK-RP is [] in the nucleus
- High levels of [] will remove the repressor, followed by [] of the now [] protein to the cytosol
- inactive
- Glucose
- translocation
- Active
- Increased levels of [] promote translocation of glucokinase to the nucles…making it more []
- Fructose 6-Phosphate
- inactive
What does Glucose 6-phosphatase do?
Converts Glucose 6-phosphate to Glucose….in the liver
What are the benefits of the futile cycle in the liver of: Glucose < —> Glucose 6-phosphate?
- Phosphate pools are finite and Glucose 6-phosphatase remakes phosphates
- Provides fine control for directionality of the system.
What is the “first committed” step of Glycolysis?
What type of regulation is it subject to?
- Fructose 6-Phosphate –> Fructose 1,6-Bisphosphate
- done by 6-phosphofructo-1-kinase
- Allosteric regulation
What are the positive/negative effector molecules on 6-phosphofructo-1-kinase?
- Positive
- AMP
- Fructose 2,6-Bisphosphate
- Negative
- ATP
- Citrate
- H+
How is AMP a negative effector molecule in Gluconeogenesis?
- AMP binds to 6-phosphofructo-1-kinase as an effector
- Higher levels of AMP negatively effect Fructose 1,6-bisphosphatase (step in Gluconeogenesis)
- If you were to remove AMP as an effector molecule it would then stop glycolysis and change to gluconeogenesis
If pH levels climb too high, what will happen to glycolysis?
Where is H+ an effector molecule in Glycolysis?
- Glycolysis will shut off if pH levels rise too much from the production of Lactate and H+
- H+ will act as an effector molecule on 6-phosphofructo-1-kinase
With abundant energy supplied by lipids, glycolytic pathway is [] regulate so that blood [] levels can be maintained for tissue not able to oxidize lipids.
- down
- glucose
Fructose 2,6-bisphosphate is a [] regulator of 6-phosphofructo-1-kinase and a [] regulator of fructose 1,6-bisphosphatase
- Positive
- negative
What bifunctional enzyme creates Fructose 2,6-bisphosphate?
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase
What bifunctional enzyme creates Fructose 6-phosphate from Fructose 2,6-bisphosphate?
6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase
6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase is [] regulated by phosphorylation/dephosphorylation….
Covalently
When 6-PF-2-K/F-2,6-P’ase is phosphorylated, which part of the enzyme is active?
What is going on with Blood Glucose when this happens?
What enzyme does the phosphorylating here?
- F-2,6-P’ase is active, meaning your creating Fructose 6-Phosphate from Fructose 2,6-bisphosphate
- Increased levels of Glucagon, which means LOW blood glucose
- Protein Kinase A
- When 6-PF-2-K/F-2,6-P’ase is dephosphorylated, which part of the enzyme is active?
- What is going on with Blood Glucose when this happens?
- What enzyme does the dephosphorylating here?
- 6-PF-2-K is active when the enzyme is dephosphorylated
- Blood Glucose would be higher at this point
- Phosphoprotein phosphatase
How does Glucagon affect the levels of F-2,6-BP?
- Glucagon activates adenylate cyclase
- Adenylate cyclase converts ATP into cAMP
- cAMP activates protein kinase A => PKA phosphorylates 6-PF-2-K/F-2,6-P’ase causing the production of Fructose 6-phosphate from Fructose 2,6-bisphosphate
Insulin counters Glucagon by activation of this cAMP destrtorying enzyme - [] []…
cAMP phosphodiesterase
The kinase mediated signaling cascade within the cell caused by Inulin targets 3 “things” for regulation at once.
What are these targets and how does the cascade effect each?
- cAMP –>AMP - positive effect, increasing AMP
- cAMP activating Protein Kinase A
- represses protein Kinase A
- Phosphoprotein Phosphatase
- positive effect - leads to the dephosphorylation of PH-2-K/F-2,6-BP
How does insulin effect glycolysis in response to high blood glucose?
- It creates AMP from cAMP - this positively effects 6-PF-1-K in glycolysis
- It inhibits Protein Kinase A activity => increase in activity from phosphoprotein phosphotase => which means more Fructose 2,6-BP is produced because that bifunctional enzyme is dephosphorylated by Phosphoprotine phospotase.
- Fructose 2,6-BP is a positive effect like AMP.
[] and [] Use G proteins to activate adenylate cyclase causing the proudction of cAMP and the activation of Protein Kinase A…
Glucagon and Epinephrine
