Chapter 24 Glycogen Degradation

Both epinephrine and glucagon stimulate glycogen breakdown by interacting with specific seven-transmembrane receptors, initiating a cAMP signal-transduction cas- cade that ultimately activates glycogen phosphorylase. Glucagon activates glycogen breakdown in the liver. Epinephrine primarily activates glycogen breakdown in the muscle. Epinephrine can also act on the liver by initiating both the cAMP cascade and a phosphoinositide cascade.

Compare and contrast the action of epinephrine and glucagon in glycogen metabolism.

a) Yes; phosphorylase would act on amylose by removing one glucose residue at a time from the nonreducing end. (b) No; the rate of degradation of amylose would be much slower than that of glycogen because amylose would have only a single nonreducing end available for reaction, whereas glycogen has many nonreducing ends.

Consider the enzymatic degradation of amylose, a linear α-1,4 polymer of glucose that is a storage form of glucose in plants. (a) Would phosphorylase act on amylose? Explain. (b) Would the rates of glucose 1-phosphate release from an amylose molecule by phosphorylase relative to that from a glycogen molecule having an equivalent number of glucose monomers be equal? Explain.

Protein kinase A, which is itself activated by cAMP, phosphorylates and activates phosphorylase kinase. Phosphorylase kinase can also be activated by the binding of Ca2 to its calmodulin subunit. On binding Ca2, calmodulin undergoes conformational changes that activate the phosphorylase kinase. The activated kinase then activates glycogen phosphorylase. These effects lead to glycogen degradation in active muscle.

Explain the roles of protein kinase A and calmodulin in the control of phosphorylase kinase in the muscle.

The phosphorolytic cleavage of glycogen produces glucose 1-phosphate, which can enter into the glycolytic pathway after conversion to glucose 6-phosphate. These reactions do not require ATP. On the other hand, the hydrolysis of glycogen produces glucose, which must be converted to glucose 6-phosphate by hexokinase, requiring the expenditure of an ATP molecule. Therefore, harvesting the free energy stored in glycogen by phosphorolytic cleavage rather than a hydrolytic one is more efficient be- cause it eliminates the need for the ATP.

Explain why the phosphorolytic cleavage of glycogen is more energetically advanta- geous than its hydrolytic cleavage.

(b)Glycogen, as the substrate, binds to the active site of the enzyme in muscle and liver; there is also a glycogen particle binding site that keeps the enzyme attached to the glycogen granule. (e) AMP binds to an allosteric site and activates phosphorylase b in muscle. (f) Pi binds to the pyridoxal phosphate at the active site of phosphosylase in muscle and liver and attacks the α-1,4 glycosidic bond. Another Pi is covalently bound to serine 14 by phosphorylase kinase in both tissues. This phosphorylation converts phosphorylase b into active phosphorylase a both in liver and in muscle. (g) ATP binds to the same site as AMP and blocks its effects in muscle; therefore, energy charge affects phosphorylase activity. (h) Glucose inhibits phosphorylase a in the liver by changing the conformation of the enzyme to the inactive T form. Answers (a) and (d) are incorrect because calmodulin and Ca2 bind to phosphory- lase kinase rather than to phosphorylase.

Indicate which of the following substances have binding sites on phosphorylase. For those that do, give their major roles or effects on the liver or the muscle enzyme. (a) calmodulin (b) glycogen (c) Ca2 (d) AMP (e) Pi (f) ATP (g) glucose

(a) 2, 4 (b) 1, 3 (c) 1, 2, 5. None of these enzymes requires ATP.

Match the enzymes that degrade glycogen (a-c) with the appropriate properties (1-6). (a) Phosphorylase (b) α-1,6-Glucosidase (c) Transferase (1) is part of a single polypeptide chain with two activities. (2) cleaves α-1,4 glucosidic bonds. (3) releases glucose. (4) releases glucose 1-phosphate. (5) moves three sugar residues from one chain to another. (6) requires ATP.

c. A glucose molecule that is degraded in the glycolytic pathway to two pyruvate mol- ecules yields two ATP molecules per glucose; however, the formation of glucose-1-P from glycogen does not require ATP needed for the formation of glucose-6-P from glu- cose. Thus, the net yield of ATP for a glucose residue derived from glycogen is three ATP molecules.

Starting from a glucose residue in glycogen, how many net ATP molecules will be formed in the glycolysis of the residue to pyruvate? (a) 1 (b) 2 (c) 3 (d) 4 (e) 5

b

The activity of which of the following enzymes is NOT required for the release of large amounts of glucose from liver glycogen? (a) glucose 6-phosphatase (b) fructose 1,6-bisphosphatase (c) α-1,6-glucosidase (d) phosphoglucomutase (e) glycogen phosphorylase

Break it down via glycolysis OR in the liver you can remove the phosphate group to transport it to other tissues (or PPP)

What can you do with Glucose 6-phosphate?

A storage molecule, a polymer of glucose. A temporary way to get through though times energetically speaking.

What is glycogen?

Glucose 6-phosphate.

What is the final product of glycogen breakdown?

When you have no more glucose! You need glucose for specific tissues to work properly (brain, RBC).

When do you need to break down glycogen?

When you have an excess of glucose! For example, after a large meal of only eggrolls!

When do you need to synthesize glycogen?

Alpha-1,6 Glucosidase.

Which enzyme cleaves the alpha-1,6 glycosidic bond of the branch point?

Phosphoglucomutase

Which enzyme converts glucose 1-phosphate into the usable glucose 6-phosphate?

Transferase

Which enzyme transfers a small oligosaccharide near the branch point to a nearby chain making it accessible to phosphorylase?

Glycogen Phosphorylase!

Which enzyme, involved in glycogen degradation, can only cleave alpha-1,4 glycosidic bonds?

a,b

Which of the following are properties of phosphoglucomutase? (a) It has a phosphoenzyme intermediate. (b) It uses glucose 1,6-bisphosphate intermediate. (c) It is an enzyme unique to glycogen metabolism. (d) It transfers the phosphate group from one position to another on the same molecule.

b,c,d

Which of the following statements about glycogen storage are NOT correct? (a) Glycogen is stored in muscles and liver. (b) Glycogen is a major source of stored energy in brain. (c) Glycogen reserves are less rapidly depleted than fat reserves during starvation. (d) Glycogen nearly fills the nucleus of cells that specialize in glycogen storage. (e) Glycogen storage occurs in the form of dense granules in the cytoplasm of cells.