Glycogen Metabolism - General

Question 1

What are the two types of linkages between glucose residues in glycogen? Which corresponds to linear? Which to branched?

Answer 1

a-1,4 glycosidic (linear) and a-1,6 glycosidic (branched) bonds

Question 2

What end of the glucose strand does glycogen synthesis and breakdown occur?

Answer 2

Non-reducing end.

Question 3

What is the input of energy for each glucose added? What will be the energy yield per molecule of glucose-6-P?

Answer 3

Input is 2 ATP. Energy yield is 31 ATP.

Question 4

The glycogenesis pathway uses an activated form of glucose: _____, to add glucose units to glycogen. This is not seen in the glycogenolytic pathway.

Answer 4

UDP-glucose.

Question 5

What molecule is a common intermediate between the synthesis and degradation of glycogen? What else does this molecule help do in the realm of glycogen metabolism?

Answer 5

Glucose-6-P. It also helps connect glycogen metabolism with glycolysis, gluconeogenesis, and/or the PPP.

Question 6

UDP-glucose is used as the _____ in glycogenesis. Briefly describe what this is.

Answer 6

Activated precursor. It is a type of substrate that allows a molecule to participate in specific reactions.

Question 7

The enzyme that converts glucose to glucose-6-P in muscle is:

Answer 7

Hexokinase.

Question 8

The enzyme that converts glucose-6-P to glucose-1-P is:. This will occur when (synthesis/degradation) is needed.

Answer 8

Phosphoglucomutase. Synthesis.

Question 9

The enzyme that converts glucose-1-P to UDP-glucose is:. This reaction also releases _____. which when hydrolyzed, drives many biosynthetic reactions.

Answer 9

UDP-glucose pyrophosphorylase. Pyrophosphate (PP_i).

Question 10

How does a glycogen molecule get started?

1. What protein?
   
   • Describe it.
2. What does it do?

Answer 10

1. Glycogenin. It is a dimer of two identical subunits.
2. It is able to synthesize an oligosaccharide about 10-20 glucose molecules long using UDP-glucose as the substrate which is bound to a tyrosine residue on the protein.

Question 11

What protein extends the glucose strand? What bonds does it create? How many glucose must be present before it can start to work?

Answer 11

Glycogen synthase. It creates a-1,4 linkages, and it requires at least 4 glucose units before it can begin to add more glucose units.

Question 12

What protein creates the branch points? How does it do this? How many residues apart must branch points be and what is the average distance?

Answer 12

Branching enzyme. It hydrolyzes an a-1,4 linkage, removing a strand of about 7 residues, and reattaches it using an a-1,6 linkage. Branch points must be 4 residues away, and it averages 8-12 residues apart.

Question 13

What 2 ways is glycogen synthase regulated? How do these regulate glycogen synthase?

Answer 13

1. Glucose-6-P: strong allosteric activator.
2. Phosphorylation
   
   • Unphosphorylated: a form (active)
   • Phosphorylated: b form (passive)

Question 14

What two hormones influence the phosphorylation state of glycogen synthase?

Answer 14

Insulin and glucagon.

Question 15

1. What is the principle enzyme that degrades glycogen?
2. What reaction does this enzyme undergo and why?
3. What are the products of this reaction?
4. What about glycogen’s structure causes an issue for this enzyme?

Answer 15

1. Glycogen phosphorylase.
2. A phosphorolysis reaction. By using this reaction, the released sugar (glucose-1-P) is phosphorylated, and does not need to be phosphorylated again at the expense of ATP to enter glycolysis.
3. Glucose-1-P and a glycogen molecule 1 residue shorter.
4. The branch points.

Question 16

Where does glycogen phosphorylase stop before a branch point? An enzyme called debranching enzyme takes over, and it has two activities. What are the two activities and what do each of them do specifically?

Answer 16

Glycogen phosphorylase stops 4 residues before a branch point.

1. Transferase: removes the three terminal glucose residues in a block and transfers them to another branch where they can be acted on by glycogen phosphorylase.
2. a-1,6 glucosidase: hydrolyzes the remaining a-1,6 linkage, releasing a free glucose molecule (not glucose-1-P)

Question 17

What happens to glucose-1-P released by glycogen degradation in the liver?

Answer 17

It is converted to glucose-6-P by phosphoglucomutase, acted on by glucose-6-phosphatase and released as glucose into the blood.

Question 18

What happens to glucose-1-P released by glycogen degradation in the muscle?

Answer 18

It is converted to glucose-6-P by phosphoglucomutase, and metabolized through glycolysis for ATP production.

Question 19

How is liver glycogen phosphorylase regulated? Describe each method. If there are enzymes, mention them.

Answer 19

1. Phosphorylation: GP exists as a dimer, and each subunit can be phosphorylated on a serine to convert it to a more active form.
   
   • Phosphorylation (a form): phosphorylase kinase
   • Dephosphorylation (b form): phosphorylase phosphatase
2. Allosteric regulation (glucose): can bind to either the a or b form and inactivate it.

Question 20

How is muscle phosphorylase regulated differently than in the liver? What does this produce? How do these products affect muscle phosphorylase?

Answer 20

Muscle phosphorylase has different allosteric regulators. Muscle phosphorylase has to be activated during contraction to provide glucose as fuel to produce ATP. When ATP is consumed, AMP levels increase.

• AMP: activates
• ATP: inhibits

Question 21

What two hormones trigger glycogen breakdown? When do each of them work? What do they both set off? What does this then do?

Answer 21

1. Epinephrine: when a quick burst of energy is needed that will require sudden contraction.
2. Glucagon: secreted by pancreas in response to low blood sugar.

Each of them trigger the cAMP regulatory cascade. This activates phosphorylase kinase, phosphorylating phosphorylase b converting it to the a form.

Question 22

What does protein phosphatase 1 do for glycogen metabolism? What 3 proteins does it work on and what is the result?

Answer 22

Reverses the effects of kinases. It removes phosphate groups from:

1. Phosphorylase kinase: inactivating and inhibiting glycogenolysis.
2. Glycogen phosphorylase: inactivating and inhibiting glycogenolysis.
3. Glycogen synthase: increasing its activity and stimulating synthesis.

Question 23

What does insulin do for glycogen metabolism? (4)

Answer 23

1. Insulin stimulates glycogen synthesis by reducing the phosphorylation state of glycogen synthase.
2. It increases the number of glucose transporters (GLUT4) on the cell membrane.
3. Inactivates glycogen synthase kinase.
4. Binding to it’s receptor leads to the phosphorylation and formation of a second messenger called insulin receptor substrate, which activates certain protein kinases.

Question 24

How does glucose regulate the enzymes of liver metabolism? (3 steps)

Answer 24

1. When blood glucose levels go up, insulin is released and our cells take it up to store most as glycogen.
2. Glucose binds to phosphorylase a, which then allows it to be converted to phosphorylase b by PP1.
3. PP1 does not attach to the b form, causing it to detach and bind glycogen synthase, dephosphorylating and activating it.