5C- Formation/Degradation of Glycogen

Question 1

What is the structure of glycogen in the liver and muscle?

Answer 1

A branched glucose polysaccharide composed of chain of glucosyl units linked by a-1,4 bonds with a-1,6 branches every 8-10 residue

Question 2

What is the function of glycogen in the liver?

Answer 2

First and immediate source to maintain blood glucose during fasting or exercise

Question 3

What is the function of glycogen in the muscle?

Answer 3

Used to generate ATP for muscle contraction

Question 4

What is the role of glucose-6-phosphatase?

Answer 4

ONLY IN THE LIVER. It hydrolyzes G6P to glucose.

Question 5

Give the steps of glycogen synthesis from glucose.

Answer 5

Glucose –hexokinase–> G6P G1P –> reacts with UTP –UDPglucose phosphorylase–> UDP-glucose –> glycogen synthase transfers glucose residues from UDP glucose to the non-reducing ends of the glycogen primer

Question 6

How does the glycogen form branches?

Answer 6

Basically, you lengthen the polysaccharide chains of a preexisting glycogen molecule at an alpha-1,4-glucose. When the chain reaches 11 residues in length, a transferease cleaves 6-8 residues and glucose synthase attaches it to a glycosyl unit by an alpha1,6 bond.

Question 7

Why do we branch glycogen?

Answer 7

Increase sites for synthesis & degradation

Enhance the solubility of the molecule

Question 8

Why is glucose-6-phophatase important in the liver?

Answer 8

Glucose 6-phosphatase is important because it is turns Glucose 6 phosphate into glucose to maintain the blood glucose in our body

Question 9

What is the role of glycogen phosphorylase in glycogen breakdown?

Answer 9

Removes glucose residues, one at a time from the nonreducing ends of glycogen molecule
It add phosphate to the anomeric carbon of the terminal glycosidic bond to cleave a-1,4 bonds, producing glucose 1 phosphate
It can continue to hydrolyze a-1,4 linkages until it reaches a point four glucose residue from an a-1,6branch

Question 10

What is glycogen phosphorylase activated by?

Answer 10

It is activated by covalent modification (opposite of glycogen synthase)and is referred to as glycogen phosphorylase A and when it is inactive, it is referred to as glycogen phosphorylase B

Question 11

What is the role of the debrancher enzyme in glycogen breakdown?

Answer 11

The last glucose unit at the branch point, which is linked a-1,6 bond, is hydrolyzed by a-1,6-glucosidase forming free glucose

Question 12

Name the enzyme, organ, and clinical manifestations of Type Ib (Von Gierkes) disease.

Answer 12

E- glucose 6-phoshatase. O-liver. M-hepatomegaly, grwoth failure, fasting hypoglycemia.

Question 13

Name the enzyme, organ, and clinical manifestations of type II (Pompe) disease.

Answer 13

E-lysosomal alpha-glucosidase. O-all organs with lysosomes. M-muscle hypotonia, cardiac failure, death, myopathy, muscular dystrophy.

Question 14

Name the enzyme, organ, and clinical manifestations of type III disease.

Answer 14

E-debrancer enzyme (amylo 1,6-glucosidase). O- liver, SkM, heart. M- fasting hypoglycemia, hepatomegaly, myopathic features.

Question 15

Name the enzyme, organ, and clinical manifestations of type IV (Anderson) disease.

Answer 15

You enter get stuck in the matrix, Neo. E-branching enzyme (amylo 4,6 glucosidase). O- liver. M- hepatosplenomegaly, death.

Question 16

Name the enzyme, organ, and clinical manifestations of type V (McArdles) disease.

Answer 16

E- muscle glycogen phosphorylase. O- SkM. M- excercise induced muscular pain, cramps, and progressive weakness, someitmes with myoglobinuria.

Question 17

How does epinephrine regulate glycogen metabolism in the liver and SkM?

Answer 17

Degradation of liver glycogen is activated by epinephrine as well as blood glucose level(glucagon). Epinephrine is released in response to exercise, hypoglycemia or other stress situations in which there is an immediate demand for blood glucose. Epinephrine will also activate skeletal muscle glycogenolysis.

Question 18

How do changes in insulin and glucagon during the fasting states regulate metabolism of glycogen in the liver?

Answer 18

An increase in glucagon and decrease in insulin during fasting state initiates a cAMP-directed phosphorylation cascade
phosphorylation of glycogen phosphorylase to an active enzyme (degradation stimulated)
phosphorylation of glycogen synthase to an inactive enzyme (synthesis inhibited)

Question 19

How does the change in 2nd messengers in the glucagon pathway activate glycogenolysis?

Answer 19

Protein kinase A phosphorylates phosphorylase kinase making it active (using ATP)
Then phosphorylated phosophorylase kinse phosphorylates glycogen phosphorylase B making it active to glycogen phosphorylase A. (Using ATP and phosphate from ATP is transferred onto the activated glycogen phosphorylase A) & glycogenolysis is stimulated
Inhibition of glycogen synthase and activation of glycogen phosphorylase, glycogen is degraded to glucose 1-phosphate

Question 20

What is the mechanism of epinephrine when it acts through β-agonist receptors?

Answer 20

Epinephrine acting at the β receptors, transmits a signal through G-protein to adenylate cylcase
Adenylate cyclase will increase cAMP and activate protein kinase A (similar to glucagon)

Question 21

What is the mechanism of epinephrine when it acts through α-agonist receptors?

Answer 21

Gq pathway to activate Ca:CAM complex, which activates both phosphorylase kinase (activates glycogen phosphorylase) and CAM-dependent protein kinase (inactivates glycogen synthase)

Question 22

What pathway does insulin activate in the liver?

Answer 22

Insulin will activate hepatic PP-1 through the insulin receptor tyrosine kinase phosphorylation cascade
Hepatic PP1: major protein phosphatases involved in glycogen metabolism.
It removes phosphate groups from phosphorylase kinase, glycogen phosporylase and glycogen synthase.
Insulin also may activate the phosphodiesterase that coverts cAMP to AMP
Decreasing cAMP and inactivating protein kinase A

Question 23

What is the role of Ca++ in muscle and liver glycogen metabolism?

Answer 23

• Sarcoplasmic reticulum release Ca2+
• Ca2+ comes together with calmodulin= Ca2+Calmodulin
• Ca2+Calmodulin activates phosphorylase kinase