Glycogen Metabolism II

Question 1

Regulation of glycogen metabolism is important for maintaining ___ ____ and providing ____ ___ ____

Answer 1

Blood sugar

Energy to muscles

Question 2

Are the pathways for glycogen synthesis and degradation independent? If so, what does this allow for?

Answer 2

Yes, which allows for separate regulation

Question 3

What are the 2 key enzymes in glycogen metabolism?

Answer 3

Glycogen synthase- rate-limiting step for synthesis

Glycogen phosphorylase- rate-limiting step for degradation

Question 4

How are Glycogen synthase and Glycogen phosphorylase regulated?

Answer 4

Allosteric regulators

Reversible phosphorylation (under the control of hormones)

*Note that the effects are in opposite directions

Question 5

During the regulation of Glycogen Synthesis, what is the active and inactive form of glycogen synthase?

Answer 5

Active- Nonphosphorylated “a” form

Inactive- Phosphorylated “b” form

Question 6

What enzyme phosphorylates Glycogen Synthase?

Answer 6

Glycogen Synthase Kinase (GSK)

Question 7

What controls the activity of GSK?

Answer 7

Insulin and PKB (protein kinase B)

Question 8

What is another regulator of Glycogen Synthase? Describe its effects and what type of regulation is this?

Answer 8

Glucose-6-Phosphate

Activates Glycogen Synthase by allosteric regulation

Question 9

During the regulation of Glycogen Breakdown, what is the active and inactive form of glycogen phosphorylase? Describe the location of the active/inactive form.

Answer 9

Active “a” form (R relaxed state)- in the liver Phosphorylated

Inactive “b” form (T tense state)- in muscle Dephosphorylated

Question 10

Describe the regulation of Glycogen phosphorylase.

Answer 10

Several Allosteric effectors- signal energy state of the cell

Phosphorylation- responsive to hormones

Question 11

The liver enzyme Glycogen Phosphorylase “a” is inactivated by what? What is it unaffected by?

Answer 11

Inactivated by free glucose (an indicator of blood sugar levels)

Unaffected by AMP

Question 12

The muscle enzyme Glycogen Phosphorylase “b” is allosterically activated by what?

Answer 12

AMP (a measure of the low energy status of the cell)

ATP that is consumed by active muscle creates AMP, which stimulates the breakdown of glycogen for energy.

Question 13

What are 2 negative allosteric regulators of muscle Glycogen Phosphorylase “b”?

Answer 13

ATP

Glucose-6-Phosphate

Question 14

What are the 3 conditions that favor Glycogenesis and in what state does this occur in?

Answer 14

High blood glucose
High insulin levels
High cellular ATP levels

Favored during the fed state

Question 15

What are the 2 conditions that favor Glycogenolysis during the fasting state?

Answer 15

Low blood glucose

High glucagon

Question 16

What are the 2 conditions that favor Glycogenolysis during the exercise?

Answer 16

High cellular calcium (in exercising muscle)
High AMP (from the breakdown of ATP)

Question 17

What are the forms of glycogen synthase and glycogen phosphorylase during the breakdown of glycogen (glycogenolysis)?

Answer 17

The phosphorylated form of glycogen synthase (inactive)

The phosphorylated form of glycogen phosphorylase (active)

Question 18

What kind of receptor is Insulin?

Answer 18

Tyrosine Kinase Receptor** Test Question

Question 19

During the activation of glycogen synthase via Insulin, what does insulin activate? Describe the rest of the activation cascade for glycogen synthase. Where are these insulin receptors found?

Answer 19

Insulin activates Protein Kinase B

PKB stimulates Protein Phosphatase 1, which dephosphorylates Glycogen Synthase and activates it

PkB also inhibits Glycogen Synthase Kinase 3 (GSK3), which when active would inhibit GS

GS stimulates glycogen formation

*This all occurs in both muscles and in the liver

Question 20

During the inactivation of glycogen phosphorylase via Insulin, what does insulin activate? Describe the rest of the activation cascade for glycogen phosphorylase. Where are these insulin receptors found?

Answer 20

Insulin activates Protein Kinase B

PkB stimulates Protein Phosphatase 1 to dephosphorylate Glycogen Phosphorylase (which inactivates it)

Glycogen phosphorylase is inactivated now

*This occurs in both the muscles and in the liver

Question 21

During insulin activation, what does PkB also stimulate to increase the activation of Glycogen Synthase?

Answer 21

PkB stimulates the translocation of GLUT4 (in muscles), which is used to bring Glucose into the cell

*Remember that G6P activates GS allosterically

Question 22

What is the net result for the activation of Insulin?

Answer 22

Glycogen synthesis via activation of glycogen synthase and inactivation of glycogen phosphorylase

Question 23

What are the 4 key proteins involved in the regulation of insulin?

Answer 23

GLUT4- in muscles only
Protein Kinase B (PkB)
Protein Phosphatase 1 (PP1)
Glycogen Synthase Kinase 3 (GSK3)

Question 24

Describe Type 2 diabetes.

Answer 24

Reduced sensitivity to insulin AKA insulin resistance

Question 25

What 3 problems can cause down-regulation in insulin receptor levels?

Answer 25

Triggered by elevated insulin Endocytosis and degradation of the insulin receptor Defective receptors not replaced by translation

Question 26

What are the 3 blood glucose criteria for: Normal patients Prediabetic/at risk Diabetes Mellitus patients

Answer 26

Normal patients: 70-100 mg/dL (fasting), ≤140 mg/dL (fed) Prediabetic/at risk: 100-125 mg/dL (fasting), >140 mg/dL (fed) Diabetes Mellitus patients: ≥126 mg/dL (fasting), ≥199 mg/dL (fed)

Question 27

What are the 2 hormones that control Glycogen Phosphorylase? What stimulates the release of these hormones and where do they act?

Answer 27

Low blood sugar levels release Glucagon- acts on the liver Muscle activity releases Epinephrine- effects are on the muscle

Question 28

What type of receptors responds to the hormones glucagon and epinephrine used to control Glycogen phosphorylase? What does this stimulate?

Answer 28

G Protein-Coupled Receptors (GPCRs) Stimulates breakdown of glycogen (glycogenolysis)

Question 29

During the inactivation of glycogen synthase via Glucagon and Epinephrine, what do these GPCR's activate? Describe the rest of the inactivation cascade for glycogen synthase. Where are these GPCR's found?

Answer 29

Glucagon and Epinephrine both bind to their respective GPCR's and activate Adenylate Cyclase Adenylate cyclase activates cAMP cAMP stimulates PkA to inhibit Protein Phosphatase 1, therefore, leaving Glycogen Synthase in its inactive, phosphorylated state * Glucagon GPCR is found only in the liver * Epinephrine GPCR is found in both muscle and liver

Question 30

During the activation of glycogen phosphorylase via Glucagon and Epinephrine, what do these GPCR's activate? Describe the rest of the activation cascade for glycogen phosphorylase. Where are these GPCR's found?

Answer 30

Glucagon and Epinephrine both bind to their respective GPCR's and activate Adenylate Cyclase Adenylate cyclase activates cAMP cAMP stimulates PkA to inactivate Protein Phosphatase 1, therefore, leaving Glycogen Phosphorylase in its active, phosphorylated state PkA also activates Phosphorylase Kinase, which phosphorylates Glycogen phosphorylase and activates it * Glucagon GPCR is found only in the liver * Epinephrine GPCR is found in both muscle and liver

Question 31

What is the net result of the regulation by glucagon?

Answer 31

Glycogen breakdown via inactivation of glycogen synthase and activation of glycogen phosphorylase

Question 32

What are the 5 key enzymes and second messengers involved in the regulation by glucagon?

Answer 32

``` GPCR's Adenylate Cyclase and cAMP Protein Kinase A (PKA) Protein Phosphatase 1 (PP1) Phosphorylase Kinase (PK) ```

Question 33

During the regulation by epinephrine, what are the 4 allosteric regulators? What are their effects?

Answer 33

G6P- activates glycogen synthase, inactivates glycogen phosphorylase Free glucose- inhibits glycogen phosphorylase in liver but not muscle **Ca2+- activates glycogen phosphorylase kinase **AMP- activates glycogen phosphorylase (especially during periods of exercise)

Question 34

What is the off switch for glycogenolysis?

Answer 34

Shutting down the secretion of hormones Phosphorylase Kinase and Glycogen Phosphorylase are inactivated Breakdown of glycogen stops Synthesis of glycogen is promoted

Question 35

Glucagon does NOT act on ______

Answer 35

Muscle!

Question 36

What happens to Glucose 1 phosphate in the liver?

Answer 36

In the liver, Glu-1-phosphate is converted to G6P and then to glucose by Glucose 6 phosphatase. Free glucose is then released into the bloodstream.

Question 37

Glucose 1 Phosphate can be converted to free glucose in the liver and released into the bloodstream. Why can't it do this in muscles? What happens to G1P in muscles?

Answer 37

Cardiac and skeletal muscles lack glucose 6 phosphatases and therefore cannot hydrolyze G6P. Glucose 1 phosphate is converted to glucose 6-phosphate in muscles. G6P can't leave muscle cells so instead it is used to generate energy via glycolysis and TCA cycle.

Question 38

______ _______ is the glucose sensor in liver cells.

Answer 38

Glycogen Phosphorylase