Chapter 13 The Glycogen Metabolism

Question 1

What is glycogen?

Answer 1

a storage carbohydrate of glucose.

Question 2

What are our major sources of glucose for metabolism?

Answer 2

ingested glucose, gluconeogenesis, and glycogen

Question 3

Why is glucose stored in the form of glycogen as opposed to free glucose?

Answer 3

to avoid osmotic shock

Question 4

Why do we need glycogen?

Answer 4

storing glucose allows for a quick release of energy rich molecules for those organs that absolutely depend upon it.

Glucose can be metabolized in the absence of oxygen, so our muscles can use it when we are oxygen deficit.

Question 5

Where can we find glycogen?

Answer 5

mostly skeletal muscle and liver.

Question 6

How is glycogen classified?

Answer 6

glycogen is a branched homopolysaccharide.

contains alpha (1–>4) linked glucose subunits

contains alpha (1—>6) branches

Question 7

Is glycogenin an enzyme?

Answer 7

pseudo enzyme

Question 8

What is the limitation of glycogenin?

Answer 8

glycogenin is used to start the process but once the glycogen chain is longer it does not fit in the active site.

Question 9

What is function of phosphoglucomutase?

Answer 9

interconversion of glucose-6-phosphate and glucose-1-phosphate

glucose-1-phosphate to glucose-6-phosphate

Question 10

Glucose entry reactions

Answer 10

1. glucose to glucose-6-phosphate catalyzed by hexokinase
2. glucose-6-phosphate to glucose-1-phosphate by phosphoglucomutase.
3. glucose-1-phosphate to UDP glucose, PPi leaving group

Question 11

What does the priming step of glycogen synthesis involve?

Answer 11

The OH of a tyrosine residue connected to glycogenin carries out a nucleophilic attack on the oxygen of UDP-glucose. PPi is leaving group.

In the subsequent steps the 4’-OH carries out the nucleophilic attack on another UDP glucose continuing the process.

Question 12

What happens to glycogenin after 6-8 UDP-glucoses have been added?

Answer 12

The chain is too large, glycogenin does not fit, glycogen synthase comes in and does the same job that glycogenin was doing.

Question 13

What is the job of the glycogen branching enzyme?

Answer 13

It will cut an alpha 1-4 bond typically 4 glucose units and then form an alpha 1-6 connection. Glycogen synthase will start to extend the branches as well.

Question 14

Are branching enzymes regulated?

Answer 14

Branching enzyme is unregulated, branches are added as needed

Question 15

Glycogen phosphorylase

Answer 15

a phosphoric acid does nucleophilic attack on carbon 1, this gives us glucose-1-phosphate and glycogen shortened by one reside.

Question 16

How many times does glycogen phosphorylase phosphorylate the glycogen?

Answer 16

glycogen phosphorylase removes successive glucose molecules until it reaches the fourth glucose unit from a branch.

Question 17

Why can glycogen phosphorylase not act within 4 residues of a branch point?

Answer 17

due to the physical size of the enzyme not being able to reach a branch due to crowding

Question 18

Which cofactor does glycogen phosphorylase use?

Answer 18

The pyridoxal phosphate (PLP cofactor).

Question 19

What specifically does the glycogen phosphorylase use from the cofactor?

Answer 19

the phosphoric acid group

Question 20

What is the debranching enzyme used for?

Answer 20

they are used to remove glucose residues 4 units within the branch.

three glucose residues are shifted to a nearby non-reducing end and they are reattached via alpha-1-4 linkage.

the single glucose residue remaining at the branch is released as free glucose by the debranching enzyme’s alpha-1-6 glucosidase activity.

Question 21

Is glycogen phosphorylase processive or distributive?

Answer 21

Processive because it continues to act on the substrate without dissociating.

Question 22

What happens to glucose-1-phosphate in the muscle?

Answer 22

Glucose-1-phosphate is converted to glucose-6-phosphate and then directly enters glycolysis.

Question 23

What happens to glucose-1-phosphate in the liver?

Answer 23

Liver wants to send glucose from glycogen to rest of the body. Glucose-6-phosphate in liver goes to the ER lumen where the phosphate group is stripped off.

The free glucose then leaves the ER and enters the blood through the GLUT2 transporter.

Question 24

Why is glucose-6-phosphatase located in the ER?

Answer 24

if this enzyme were cytoplasmic it would remove phosphate groups off of glucose that were planning to go through glycolysis.

Question 25

How does insulin regulate glycogen synthesis?

Answer 25

insulin released when glucose is high, inhibits glycogen breakdown, and stimulates glycogen synthesis.

Question 26

How does glucagon regulate glycogen synthesis?

Answer 26

glucagon released when glucose is low. Glucagon binds to GPCR, stimulates synthesis of cAMP, activation of protein kinase A results in phosphorylation of glycogen phosphorylase stimulating glycogen breakdown.

Question 27

When is glycogen synthase active?

Answer 27

when it is not phosphorylated

Question 28

When is glycogen phosphorylase active?

Answer 28

when it is phosphorylated

Question 29

What is the glycogen code?

Answer 29

phosphorylated results in glycogen breakdown

unphosphorylated results in glycogen synthesis

Question 30

What is the regulation of glycogen metabolism by glucagon and epinephrine?

Answer 30

glucagon and epinephrine bind to a GPCR.

The GPCR undergoes a conformational change and activates G alpha s.

G alpha s activates adenylate cyclase which stimulates the synthesis of cAMP.

cAMP activates protein kinase A

Protein kinase A phosphorylates phosphorylase kinase activating it.

Phosphorylase kinase phosphorylates glycogen phosphorylase activating it.

Glycogen phosphorylase breaks down glycogen.

Question 31

Regulation of glycogen metabolism by insulin

Answer 31

insulin activates protein phosphatase-1.

Protein phosphatase-1 dephosphorylates glycogen synthase making it active.

Protein phosphatase dephosphorylates glycogen phosphorylase inactivating it and also dephosphorylates phosphorylase kinase so it cannot phosphorylate the glycogen phosphorylase.

Question 32

What is the major kinase that regulates glycogen synthase?

Answer 32

Glycogen synthase kinase

Question 33

What is the effect of GSK on glycogen metabolism?

Answer 33

GSK inhibits glycogen synthesis by phosphorylating and inhibiting glycogen synthase.

Question 34

How is the activity of GSK regulated?

Answer 34

Insulin phosphorylates IRS

Deactivation of PI3 kinase.

Generates PIP2 ligand PDK-1 and Akt to the membrane.

PDK and Akt is a kinase

Turns GSK kinas off

Glycogen synthase becomes active.

Question 35

How does insulin regulate GSK through both GSK and PP1?

Answer 35

insulin inhibits GSK and activates PP1 which activates glycogen synthase

Question 36

What is allosteric regulator of muscle glycogen phosphorylase?

Answer 36

ATP, AMP, and glucose-6-phosphate.

AMP high, favors the shift to relaxed state frees more glucose residues.

Question 37

What is allosteric regulator of liver glycogen phosphorylase?

Answer 37

glucose, glucose inhibits phosphorylase

Question 38

What are glycogen targeting proteins?

Answer 38

responsible for bringing together glycogen synthase, glycogen phosphorylase, and protein phosphatase on the glycogen particle.

Insulin results in the phosphorylation of GM, PPI is activated. Activation of PP1 results in dephosphorylation of PK, GP, and GS.

glucagon or epinehprine bind to second site and cause PP1 to dissociate from glycogen particle. PKA phosphorylates Inhibitor 1 protein which binds to and inhibits any activity of PP1.