9.5 Glycogenesis and Glycogenolysis

Question 1

Glycogen

Answer 1

• branched polymer of glucose, represents a storage form of
  glucose.
• Glycogen synthesis and degradation occur primarily in liver and skeletal muscle, although other tissues store smaller quantities

Question 2

How is glycogen stored in the cytoplasm?

Answer 2

• As granules
• Each granule has a central protein core with polyglucose chains radiating outward to form a sphere
• If the chains are branched, the
  glucose density is highest at the periphery of the granule, allowing more rapid release of glucose on demand

Question 3

Difference between glycogen in the liver and in skeletal muscle?

Answer 3

• Liver glycogen is broken down to maintain a constant level of glucose in the blood
• Muscle glycogen is broken down to provide glucose to the muscle during vigorous exercise.

Question 4

Glycogenesis

Answer 4

• the synthesis of glycogen granules
• begins with a core
  protein called glycogenin

Question 5

Glycogen Synthase

Answer 5

• the rate-limiting enzyme of glycogen synthesis and
  forms the α-1,4 glycosidic bond found in the linear glucose chains of the granule
• stimulated by glucose 6-phosphate and insulin. It is inhibited by epinephrine and glucagon through a protein kinase cascade that phosphorylates and inactivates the enzyme

Question 6

Branching enzyme

Answer 6

• responsible for introducing α-1,6-linked branches into
  the granule as it grows

Question 7

How is a branch created?

Answer 7

• Hydrolyzes one of the α-1,4 bonds to release a block of oligoglucose (a few glucose molecules bonded together in a chain), which is then moved and added in a slightly different location.
• Forms an α-1,6 bond to create a branch

-Mnemonic: α-1,4 keeps the same branch moving “4ward”; α-1,6 (one-six) “puts a branch in the mix.”

Question 8

Glycogenolysis

Answer 8

• the process of breaking down
  glycogen
• rate-limiting enzyme of glycogenolysis
• The glucose 1-phosphate formed by glycogen phosphorylase is converted to glucose 6-phosphate by the same mutase used in glycogen synthesis

Question 9

How is glycogen phosphorylase activated in liver vs skeletal muscle?

Answer 9

• Glycogen phosphorylase is activated by glucagon in the liver, so that glucose can be
  provided for the rest of the body.
• In skeletal muscle, it is activated by AMP and epinephrine, which signal that the muscle is active and requires more glucose.
• It is inhibited by ATP.

Question 10

Glycogen Phosphorylase

Answer 10

• breaks α-1,4 glycosidic bonds, releasing glucose 1- phosphate from the periphery of the granule. It cannot break α-1,6 bonds and therefore stops when it nears the outermost branch points

Question 11

Debranching enzyme

Answer 11

• a two-enzyme complex that deconstructs the branches in glycogen that have been exposed by glycogen phosphorylase
• Debranching enzyme is actually made up of two enzymes with different functions: one moves the terminal end of a glycogen chain to the branch point (α-1,4:α-1,4 transferase), and one removes the glucose monomer actually present at the branch point (α-1,6 glucosidase).

Question 12

Debranching Enzyme Pathway

Answer 12

• Breaks an α-1,4 bond adjacent to the branch point and moves the small oligoglucose chain that is released to the exposed end of the other chain.
• Forms a new α-1,4 bond.
• Hydrolyzes the α-1,6 bond, releasing the single residue at the branch point as free glucose. This represents the only free glucose produced directly in glycogenolysis (as opposed to the glucose produced from glucose 1 phosphate, which must be converted by a mutase to glucose 6-phosphate before it can be converted to glucose via the enzyme glucose-6-phosphatase).

Question 13

Isoforms

Answer 13

• slightly different versions of the same protein; in the case of glycogen enzymes, there are often different isoforms of the enzymes in the liver and muscle.