LEC D

Question 1

How is the bifunctional enzyme PFK-2/FBPase2 different in the Cardiac Muscle?

Answer 1

PKA still phosphorylates it but at different places. The Phosphatase domain (vs the Kinase end) is phosphorylated towards C terminus. That inhibits the phosphatase and the kinase remains active making F26BP activating glycolysis.

Instead of glucagon being the signal, Epinephrine, will lead to PKA activity that will Phosphorylate FBPase2 activating PFK2 making F26BP which will activate PFK1 activating glycolysis.

Therefore PKA will have the opposite effect in cardiac muscle versus the Liver where PKA deactivates PFK 2 and triggers GNG.

Question 2

PP1c is activated when which of the following occurs?

A) when it binds to glucose or glucose-6-phosphate

B) when it dephosphorylates glycogen phosphorylase

C) when it dissociates from glycogen phosphorylase

D) when it is dephosphorylated.

E) b and c

F) a and b

G) a,b, and c

Answer 2

E) when it dephosphorylates glycogen phosphorylase and when it dossociates from glycogen phosphorylase.

Question 3

In the liver when glucose is HIGH does PPC1 need be activated or deactivated? and why?

Answer 3

PP1c needs to be ACTIVATED so it can DEphosphorylate a bunch of stuff so glyocgen synthensis can occur.

Question 4

Explain the Activation of glycogen synthesis in the liver at high blood glucose starting with PP1c and inhibition of glycogen phosphorylase

Answer 4

1. PP1c is inhibited when when attached to phosphorylated glucogen phosphorylase.
2. Increasing glucose will lead to glucose binding to phosphorylated glycogen phosphorylase.
3. Conformational change in the phosphorylated glycogen phosphorylase leads to exposure of phosphate groups.
4. These will be cleaved off by PP1c leading to dissociation of PP1c and glycogen phosphorylase (which is now inhibitied).
5. PP1c activity increases and will DEphosphorylate phosphrylated glycogen synthase (activating it) and dephosphorylate phosphorylated phosphorylase kinase (inhibiting it) that way phosphorylase kinase won’t phosphorylate glycogen phosphorylase.

Question 5

What is diabetes? Type 1 and Type 2?

Answer 5

Type 1 is an autoimmune disorder resulting in the destruction of the Beta cells.

Type 2 results from insulin resistance, inadequate insulin secretion, excessive secretion of glucagon, or a combination of these factors.

Question 6

True or False: Giving a type 1 diabetic Glyburide or glipizide will be an effective medication.

Answer 6

False. Since they do not have anymore beta cells.

Question 7

How dos Glyburide and Glipizide work?

Answer 7

Glyburide and glipizide ineract with the sur subunits inhibiting the Potassium channels causing Depolarization of the cell membrance, activiting the Ca volataged gated channels and therefore increase Ca concentration inside the cell which triggers the release of insulin granuals into the blood stream.

Question 8

Under normal circumstances how is insulin released from the pancreas cells?

Answer 8

ATP, when concentrations start to rise in the pancrea’s beta cells will inhibit the potassium channel. meaning that potassium will no longer be leaking out of the cells when ATP is elevated. This will cause a DEPOLARIZATION of the cell membrane that will then open and this will allow calcium into the cell and cause insulin granules to release insulin into the blood stream.

Question 9

How does Glyburide and Glipizide work?

Answer 9

They inhibit the potassium channels just like ATP and cause DEPOLARIZATION on the cell membrane which activates the calcium channel to increase the cell’s Ca concentraion and causing insulin granules to be released.

Question 10

True or False: In the flight or fight response, the demand in ATP will skyrocket in the liver.

Answer 10

Flase: This instead will occur in the muscle. And this is because of allosteric regulation for a rapid response.

In the liver, it responds hormonally.

Question 11

How is PFK-1 allosterically regulated?

Answer 11

By low and high [] of ATP. When ATP [] are low PFK -1 activity is about 90 % of vmax.

When ATP [] are high PFK -1 activity is about 10%.

Question 12

In the muscle what inhibits PFK-1 and what activates PFK-1?

Answer 12

ATP will inhibit PFK-1 and AMP and ADP will activate PFK-1.

Question 13

How and when (active or rest) will that signal be present?

Question 14

How is phosphorylase kinase activated in the skeletal muscle?

Question 15

How does this regulate glycogen breakdown?

Question 16

How is PP1c regulated in the skeletal muscle? How does this regulate glycogen synthesis?

Question 17

When ATP binds to PKF-1 does it go to the tense state or relaxed state?

Answer 17

Tense state since ATP deactivates it.

Question 18

Scenario: You stand up and start to sprint out of the classroom and when you do that in your muscle cells there is a reposit of ATP just sitting around waiting to be used and by the time you are 10 seconds in that repository ATP is virtually gone.

How does more ATP come?

Answer 18

We start to gain more ATP from something called Creatine Phosphate aka Phosphocreatine. Creatine Phosphate can take ADP and quickly make more ATP. But this will also run out after about 3 seconds worth of energy.

Question 19

After residual ATP is used and creatine phosphate, how is ATP made to sustain the scenario of running?

Answer 19

You start tp generate ATP through Anaerobic metabolism and lactate will be created in a short period of time from glucose through glycolysis.

Question 20

ATP production through lactate fermentation is only 1/16 as efficient as oxidative phosphorylation. If glycolysis flux increases 9 fold while the cell loses the ability to carry out oxidative phosphorylation which of the following is true?

A) ATP producing capacity (from glucose) has increased 16 fold in the cell.

B) ATP prodicing capactiy (from glucose) has increased 9-fold in the cell.

C) ATP producing capacity (from glucose) has decreased 2-fold in the cell.

D) ATP producing capactiy (from glucose) has decreased 16-fold in the cell.

Answer 20

C) ATP producing capacity (from glucose) will decrease 2-fold.

Question 21

Considering the scenario of a person continuing to run, how is a 90 fold increase possible if lactate acid fermination is not enough?

Question 22

Would it be expected that FBPase-1 would be expressed in the skeletal muscle?

Answer 22

It actually is even though skeletal muscle does not perfrom GNG.

Question 23

Why is FBPase-1 found in skeletal muscle when this is not a GNG tissue?

Answer 23

FBPase-1 has magnifying effects. AMP reciprocially regulate PFK-1 and FBPase-1. It activates PFK-1 and inhibits FBPase-1. J equals Flux. Vf is velocity forward and Vr is velocity reverse. Vmax of PFK-1 is about 100. FBPase-1 vmax is about 10.

So low AMP (sitting at rest). Lost of activation of PFK-1 velocity is 10% max.

High AMP (activite)90 % of Vmax.

FBPase-1 at rest AMP is active. FBPase-1 at high AMP is the inhibitor so when active FBPase is at 10% Vmax.

Question 24

Given the introduction of FBPase-1 what is J at rest and during activity?

A) J = 9 (rest) and J = 1 (active)

B) J = 1 (rest) and J = 9 (active)

C) J = 89 (rest) and J = 1 (active)

D) J = 1 (rest) and J = 89 (active)

E) J = 10 (rest) and J = 90 (active)

Answer 24

D) J =1 (rest) and J = 89 (active). With FBPase1 an 89 X fold increase is doable.

Question 25

Given this slide we can state the following as true:

A) Pyruvate kinase is inhibited by AMP at rest.

B) Pyruvate kinase is activated by AMP during activity.

C) Pyruvate kinase is inhibited by ATP at rest.

D) Pyruvate kinase is activated by F16BP during activity.

E) A and D

F) B and C

G) C and D

Answer 25

C and D Pyruvate kinase is inhibited by ATP at rest and Pyruvate kinase is activated by F16BP.

Question 27

How does high [] of ATP regulate glycolysis in skeletal muscle? And how does low [] of ATP and high [] of AMP regulate glucolysis in the muscle cells?

Answer 27

High [] of ATP inhibits PFK and Pyruvate kinase. Low [] of ATP and high [] of AMP will activate PFK and Pyruvate kinase to increase flux through glycolysis.

Question 28

How does Fructose 1,6 bisphosphate regulated glycolysis in skeletal muscle cells?

Answer 28

It activates Pyruvate kinase in a feed forward reaction.

Question 29

What other glycolytic enzymes in skeletal muscle cells can be regulated allosterically? How and when (active or rest) will that signal be present?

Answer 29

Pyruvate Kinase and PFK. High ATP will inhibit it and low ATP will activate it. G6P will inhibit hexokinase at rest high amounts of ATP. F16BP activates Pyruvate kinase.