Glycogen metabolism - glycogenolysis

Question 1

__________________________ is a polymer of glucose found in the liver and skeletal muscle in large granules in the cytoplasm.

Answer 1

Glycogen

Question 2

What types of linkages characterize glycogen?

Answer 2

Alpha 1–>4 linkages with alpha 1–>6 linked branches

Question 3

What are the large granules full of glycogen also called?

Answer 3

Rosettes

Question 4

What is the metabolic role of glycogen?

Answer 4

Energy storage

Glucose source

Question 5

What are two problems with using fat stores as fuel?

Answer 5

1. Fats cannot be used in anaerobic conditions
2. Glucose is sole source of energy for brain

Question 6

What is the name for the breakdown of glycogen?

Answer 6

Glycogenolysis

Question 7

Glycogenolysis requires three enzymes. What are they?

Answer 7

1. Glycogen phosphorylase (GP)
2. Debranching enzyme (transferase, glucosidase)
3. Phosphoglucomutase

Question 8

What is considered to be the main enzyme responsible for glycogen degradation?

Answer 8

Glycogen phosphorylase

Question 9

How does glycogen phosphorylase operate?

Answer 9

Phosphorolysis

Question 10

What is the mechanism of glycogen phosphorylase?

Answer 10

1. Oxygen on nonreducing end kicks back to form oxonium intermediate
2. Alpha 1–>4 linkage broken, releasing glycogen n-1
3. Inorganic phosphate attacks former anomeric carbon, forming glucose-1-phosphate

Question 11

What is important about the fact that glycogen phosphorylase occurs via phosphorolysis?

Answer 11

It saves energy

Question 12

Glycogen phosphorylase activity continues until it reaches the _____ glucose from the alpha1–>6 branch point, where it stops. This leaves a “_______ _______.”

Answer 12

4th

Limit branch

Question 13

_________________ ____________ is a bifunctional enzyme that contains two active domains: a transferase and glucosidase.

Answer 13

Debranching enzyme

Question 14

The _______________ activity of the debranching enzyme moves three glucose units from a branch to a nearby non-reducing end, leaving a single glucose molecule at the branch point.

Answer 14

Transferase

Question 15

The _________________ activity of the debranching enzyme hydrolyzes the remain single glucose; approximately 10% of glucose is lost this way.

Answer 15

Glucosidase

Question 16

What enzyme uses a phosphoserine residue to form glucose-1,6-bisphosphate intermediate?

Answer 16

Phosphoglucomutase

Question 17

What happens to the glucose-6-phosphate produced from glycogen?

Answer 17

In muscle, G6P is shuttled into glycolysis for the production of ATP

In liver, G6P is dephosphorylated via glucose-6-phosphatase to glucose and released into the blood; alternatively, G6P can enter the pentose phosphate pathway

Question 18

Is the overal pathway of glycogen degradation irreversible?

Answer 18

Yes, it is irreversible and therefore regulated

Question 19

McArdle’s disease results from a defect in muscle ___________ ____________________.

Answer 19

Glycogen phosphorylase

Question 20

Cori’s disease results from a defect in ______________ ________________.

Answer 20

Glycogen debranching enzyme

Question 21

What are the symptoms of McArdle’s disease?

Answer 21

Tire easily

Exercise-induced cramping and pain

Question 22

Why do patients with McArdle’s disease tire easily and experience exercise intolerance?

Answer 22

Because they have a defect in glycogen phosphorylase, so they are unable to break down glycogen and to provide muscle cells with needed glucose

Question 23

What are the symptoms of Cori’s disease?

Answer 23

Enlarged liver

Structurally abnormal tissues and organs

Low blood sugar (hypoglycemia)

Question 24

Why do patients with Cori’s disease have an enlarged liver, abnormally structured tissues and organs, and hypoglycemia?

Answer 24

Because the defect in glycogen debranching enzyme prevents the degradation of glycogen; as such, glycogen builds up in tissues and organs leading to structural abnormalities and hypoglycemia - cells are unable to access stored glucose

Question 25

What are the treatments for McArdle’s disease and Cori’s disease?

Answer 25

McArdle’s disease - creatine supplementation, which can create ATP, or sugar feeding before exercise

Cori’s disease - frequent feedings