Carb Metab Regulation

Question 1

Which bypass is not suitable for regulation of glycolysis and why?

Answer 1

• Bypass 3

- G6P is required for other pathways

Question 2

What are good points in glycolysis for regulation?

Answer 2

• PFK

- Pyruvate Kinase

Question 3

PFK regulation

Answer 3

• PFK is in the glycolysis pathway
• Allosterically inhibited by ATP as a feedback inhibitor
• High ATP levels will turn PFK off
• High AMP/ADP levels will compete with ATP for binding at the allosteric site and signal the speeding up of glycolysis
• F2,6BP is also an activator of glycolysis (competes with ATP for binding)

Question 4

Mechanism of PFK regulation by ATP

Answer 4

• When an activator binds (AMP/ADP), stabilizing positive charges are placed near where the substrate binds
• When an inhibitor binds (ATP), destabilizing negative charges are placed near where the substrate binds.

Question 5

FBPase regulation

Answer 5

• FBPase is in the gluconeogenesis pathway

- AMP and F2,6BP will bind an allosteric site and inhibit–serves to slow gluconeogenesis while glycolysis is active

Question 6

Synthesis and breakdown of F2,6BP

Answer 6

• Regulated by bifunctional enzyme
• Dephosphorylated state: catalytic site in the kinase domain is active (PFK-2)
• Phosphorylated state: catalytic site in phosphatase domain is active (FBPase-2)
• Phosphorylation state is under hormonal control

Question 7

Impact of low blood glucose

Answer 7

low glucose–> increased glucagon secretion–> increased cAMP–> increased enzyme phosphorylation–> activation of FBPase-2 and inactivation of PRK-2–> decreased F2,6P–> Inhibition of PFK and activation of FBPase–> increased gluconeogenesis

Question 8

Impact of high blood glucose

Answer 8

high glucose–> increased insulin secretion–> decreased enzyme phosphorylation–> increased F2,6P–> increased glycolysis

Question 9

Regulation of pyruvate kinase

Answer 9

• Activated by FBP (earlier substrate of the pathway), inhibited by feedback inhibitors (Acetyl-CoA and ATP)
• Inhibited by cAMP dependent phosphorylation induced by glucagon

Question 10

Regulation of pyruvate carboxylase

Answer 10

-Activated by Acetyl-CoA

Question 11

Impact of glucagon

Answer 11

• Decrease in the level of glycolytic enzymes (glucokinase and PFK)
• Increase in gluconeogenic enzymes (PEPCK, FBPase, and G6Pase)

Question 12

Impact of insulin

Answer 12

-Decrease in level of gluconeogenic enzyme PEPCK

Question 13

Three methods of reciprocal regulation of glycolysis and gluconeogenesis

Answer 13

• Allosteric ligands (ATP, ADP, AMP, F26BP, FBP, Acetyl-CoA)
• Protein kinase/phosphatases
• Hormonal regulation

Question 14

What is the only shared enzyme in the reciprocal regulation of glycogen synthesis and breakdown?

Answer 14

-Phosphoglucomutase (converts G1P to G6P and vice versa)

Question 15

Regulation of glycogen synthesis

Answer 15

• Glycogen synthase is regulated through reversible protein phosphorylation
• Increase in cAMP activates PKA which inhibits glycogen synthase and phosphoprotein phosphatase 1
• Insulin increases glycogen synthesis

Question 16

Regulation of glycogen breakdown

Answer 16

• Glycogen phosphorylase is regulated
• Increase in cAMP activates PKA which activates phosphorylate kinase which activates glycogen phosphorylase and stimulates breakdown

Question 17

Impact of epinephrine on muscle cells

Answer 17

-Epi increases cAMP and consequently glycogen degradation.

Question 18

Impact of insulin on glucose transporters

Answer 18

• Increases Glu transporters at the cell surface and consequently the uptake of Glu
• Doesn’t occur in brain or liver
• Results in increased glycogen synthesis in the muscle
• Results in increased synthesis of triacylglycerols in adipocytes

Question 19

Allosteric regulation of glycogen phosphorylase

Answer 19

• When blood glucose is low, phosphorylase will be in the phosphorylated form (the active R conformation)
• When blood glucose is high, ATP and G6P will be high and dephosphorylated phosphorylase will be in the inactive T conformation. Can become activated if levels of AMP are high.

Question 20

Regulation of the pyruvate dehydrogenase complex

Answer 20

• Pyruvate dehydrogenase complex has its own regulatory enzymes E4 and E5 that both act on E1
• Kinase is activated by NADH and acetyl coA to phosphorylate and inactivate E1
• Pyruvate and ADP inhibit the kinase and serve to keep E1 active
• In F or F response calcium activates the phosphatase to convert E1 back to the active form
• Product inhibition of E3 by NADH and E2 by acetyl-coA

Question 21

CAC regulation

Answer 21

• Product inhibition:
• Citrate inhibits citrate synthase
• iCitrate DHase inhibited by NADH
• Alpha KG DHase inhibited by NADH and Succ-CoA
• Feedback inhibition: Cit synthase inhibited by Succ-CoA
• Allosteric inhibition: iCit DHase activated by ADP and inhibited by ATP