Glycogen Metabolism

Question 1

Main stores of glycogen?
Which stores larger amount of glycogen?
What does each of these stores use it for?

Answer 1

Muscle and liver
Muscle
Muscle=energy; liver= maintains blood glucose for liver and kidney

Question 2

All straight chains have what kind of linkages?

Answer 2

1->4 glycosidic linkages

Question 3

Difference between gluconeogenesis and glycogenesis

Answer 3

Gluconeogenesis= slow to react but reliable
Glycogenesis= significant storage with a fast response but only lasts 12-14 hours

Question 4

Two parts of your body that are dependent on glucose

Answer 4

Brain and RBC

Question 5

Why can’t muscle glycogen provide blood glucose maintenance?

Answer 5

Due to absence of glucose-6-phosphatase

Question 6

Where does glycogenesis take place?

What enzymes does glycogenesis require?

Answer 6

Cytosol

Requires glycogen synthase and branching enzyme

Question 7

What is the rate limiting enzyme for synthesis of glycogen?

Answer 7

Glycogen synthase

Question 8

What is needed to initiate glycogen synthesis?

Answer 8

Glycogen fragment/glycogenin - has tyrosine attached which auto-glycosylates (meaning it adds glucose molecules)

Question 9

Give an example of glycosylation

Answer 9

HbA1C

Question 10

In order to enter glycogenesis, why does glucose need to be activated to UDP glucose?

Answer 10

This activation is necessary so glucose does not enter glycolysis; enters glycogenesis instead (needed for branching enzyme and glycogen synthase to act)

Question 11

So once you have UDP glucose- glycogen synthase comes and does what?

Answer 11

Elongation- can only act if you have glycogenin or other small chain of glucose. Also, only works on non-reducing ends

Question 12

1. What does it mean to be a nonreducing sugar?

2. Explain which sugars are reducing/nonreducing?

Answer 12

1. Anomeric carbon is involved in formation of bond so it cannot oxidize/react (does not have an OH group)
2. First sugar is reducing end; all other sugars are nonreducing (remember: nonreducing is important for synthesis of glycogen) Nonreducing ends are the very ends of branches in this case

Question 13

When does branching enzyme come in?

What does it do?

Answer 13

When glucose chain is long enough

Forms new alpha 1->6 branch and breaks an old alpha 1->4 branch

Question 14

Importance of what branching enzyme is doing?

Answer 14

Branching enzyme is making multiple branches. Branches are helpful because they are easier to digest and take up a smaller area (liver and muscle are unable to hold long, straight chains)

Question 15

1. Glycogen synthase makes what kind of bonds?

2. Branching enzyme makes what kind of bonds?

Answer 15

1. Alpha (1->4) bonds (by further elongation at nonreducing ends)
2. Alpha (1->6) bonds (by further branching)

~this eventually makes the branched structure that is glycogen

Question 16

Glycogenolysis is not reverse of glycogenesis; separate pathway.

1. Site?
2. What two enzymes does it require?

Answer 16

1. Liver and muscle

2. Glycogen phosphorylase and debranching enzyme

Question 17

Function of glycogen phosphorylase

What is significant about this enzyme

Answer 17

Requres Pi to remove terminal sugars (nonreducing ends) one at a time. Works its way down until it gets to last 3-4 sugars from the branch point. Releases glucose as glucose-1-PO4

It is rate limiting enzyme for glycogen degradation

Question 18

Function of debranching enzyme?

Answer 18

Once you are down to terminal 3-4 sugars, debranching enzyme removes them to expose branching point

Question 19

90% of glucose is releases as glucose-1-PO4. What happens to other 10%

Answer 19

Glucose-1-PO4 converts to glucose-6-PO4. This is translocated by translocase into ER lumen where it is converted to free glucose by glucose-6-phosphatase (in liver and kidney).
GLUT2 then transports this free glucose out

Question 20

Allosteric regulation:

1. Glycogen synthesis
2. Glycogen degradation

Answer 20

1. High levels of energy and substrate

2. Low levels of energy and glucose

Question 21

Liver: would you make glycogen or degrade it if you have high levels of Glucose-6-phosphate

Answer 21

Make glycogen (check notes app)

Question 22

Muscle (this part is different than liver): high levels of what two additional things would lead to glycogenolysis

Answer 22

High Ca2+ (which would be during strenuous exercise) and high AMP (because that means low energy)

Question 23

1. Hypoglycemia would initiate what 3 hormones?
2. Hyperglycemia would initiate what hormone?
3. Stress would initiate what hormones?

Answer 23

1. Glucagon, epinephrine and GH
2. Insulin
3. Cortisol and epinephrine

Question 24

Insulin does what to key enzyme in glycogenesis?

Glucagon/epinephrine?

Answer 24

Insulin dephosphorylates key enzyme to make it glycogen synthase
Glucagon/epi phosphorylate it to make it glycogen phosphorylase

Question 25

Breakdown of glycogen is quicker with Ca or with AMP?

Answer 25

Ca

Question 26

Role of Ca2+ in muscle for glycogen degradation (think cell signaling lecture)

Answer 26

Ca is released from SR during exercise, binds to calmodulin subunit of phosphorylase kinase (activating with w/o phosphorylation) phosphorylase kinase activates glycogen phosphorylase to degrade glycogen

Question 27

Role of AMP in muscle

Answer 27

Protein kinase A phosphorylates phosphorylase which activates glycogen phosphorylase (has more steps than Ca)

Question 28

Glycogen storages diseases (GSDs) are mostly autosomal recessive conditions except

Answer 28

Liver phosphorylase kinase deficiency (GSD IX)

Question 29

Origin and consequences of GSDs

Type 1: Von Gierkes

Answer 29

Liver
G6Pase deficiency (glycogen not broken down normally)
Severe postabsorptive hypoglycemia, lactic acidemia, hyperlipidemia
Round face, hepatomegaly

Question 30

Origin and consequences of GSDs

Type II: Pompes

Answer 30

Lysosomal alpha glucosidase (Acid maltase) deficiency - accumulation of glycogen vacuoles in cytosol
Affects muscle, liver and heart
Cardiomegaly (floppy baby)
Die before 18 months usually (if doesn’t affect heart its not as severe)

Question 31

Origin and consequences of GSDs

Type III: Coris

Answer 31

Debranching enzyme deficiency

Very large liver with large stores of glycogen (limit dextrin is type of glycogen deposit in liver and muscle)

Question 32

Origin and consequences of GSDs

Type IV: Andersons

Answer 32

Branching enzyme deficiency-very severe but very rare
*problem with synthesis, not breakdown
Liver: cirrhosis/heart involvement
Usually die before age 2 (need liver transplant)

Question 33

Origin and consequences of GSDs

Type V: McArdles

Answer 33

Muscle glycogen phosphorylase deficiency so glycogen in muscle not broken down
Extreme fatigue/muscle damage causing myoglobinuria
Second wind - temporary shift from glycogen to lipids for energy

Question 34

Origin and consequences of GSDs

Type IV: Hers

Answer 34

Liver
Liver glycogen phosphorylase deficiency
Mild hypoglycemia/hepatomegaly
(Similar to type I but not as severe)