Glycogen Metabolism

Question 1

What is an essential energy source for exercising muscle and RBCs?

Answer 1

Glucose (anaerobic glycolysis)

-Also a greatly preferred energy source for brain

Question 2

What are the 3 sources blood glucose is obtained from?

Answer 2

1) Diet
2) Degradation of glycogen
3) Gluconeogenesis

Question 3

What is glycogen?

Answer 3

Body mechanism for glucose storing, rapidly mobilizable from liver and kidney
-Muscle glycogen is extensively degraded in exercising muscle

Question 4

Where are the main stores of glycogen?

Answer 4

Skeletal muscle and liver

Question 5

What is the clear distinction between use of glycogen in liver and in muscles?

Answer 5

• Liver will be controlled/regulated by blood [glucose] -> 100% concerned with body’s needs (after eating, liver will take glucose from blood and store it as glycogen so that it can maintain blood glucose in early stages of fasting)
• Muscle is more selfish and saves glucose for itself (fuel reserve) so that when it is exercising and needs glycogen -> glycolysis -> TCA -> ATP energy

Question 6

What is the structure of glycogen?

Answer 6

A branched-chain polysaccharide made exclusively from alpha-D-glucose

• Primary glycosidic bond: alpa(1->4)
• After about 8-10 residues: branch alpha (1->6) linkage
• Polymers of glucose exist in discrete cytoplasmic granules that contain most enzymes for synthesis and degradation

Question 7

What happens to liver glycogen stores during the well-fed state and during a fast?

Answer 7

Increase (accelerates glycogenesis); depleted (accelerates glycogenolysis)

Question 8

What happens to muscle glycogen stores during a fast?

Answer 8

Not affected by short periods of fasting and is only moderately decreased in prolonged fasting

• skeletal muscle glycogenolysis occurs during active exercise
• glycogenesis begins as soon as muscle is again at rest

Question 9

What is glycogenesis?

Answer 9

Synthesis of glycogen

• alpha-D-glucose attached to UDP is the source of all glucosyl residues added to growing glycogen
• UDP-glucose made from glucose 1-P and UTP by UDP-glucose pyrophosphorylase
• Pyrophosphate (PPi) hydrolyzed to 2 inorganic phosphates (Pi)

Question 10

Glycogen synthase cannot initiate chain synthesis using free glucose, instead it does what?

Answer 10

Elongates from a primer: glycogenin (protein) autocatalyzes primer formation from UDP-glucose
-glycogen synthase ONLY makes alpha (1-4) linkages

Question 11

How does glycogen synthase elongate glycogen chains?

Answer 11

Transfer from UDP-glucose to nonreducing end of growing chain, forming new glycosidic bond between the anomeric hydroxyl group of C1 of activated glucose and C4 of accepting glucosyl residue

Question 12

What enzyme is responsible for the formation of branches in glycogen?

Answer 12

Amylo-alpha(1->4)->alpha(1->6)-transglucosidase

• Removes set of 6-8 residues from nonreducing end, breaking alpha (1->4) and attaches it to non-terminal glucosyl residue by alpha(1->6)
• Functions as a 4:6 transferase
• Branches located 8 residues apart; result is a highly branched, tree-like structure

Question 13

What happens after first formation of alpha(1->6) bond in glycogen?

Answer 13

Further elongation at the nonreducing end by glycogen synthase, making alpha(1->4) bonds
-Their terminal 6-8 residues can be removed and used to make further branching, making alpha (1->6) bonds

Question 14

T or F: The degradation of glycogen (glycogenolysis) is simply a reversal of the synthetic reactions.

Answer 14

False; a separate set of cytosolic enzymes is required for glycogenolysis

Question 15

What is the primary product of glycogenolysis?

Answer 15

G-1-P: obtained by breaking alpha (1->4) bonds

-some free glucose is released from each alpha(1->6)-linked glucosyl residue

Question 16

What enzyme cleaves alpha(1-4) bonds?

Answer 16

Glycogen phosphorylase

• By simple phosphorolysis (producing G-1-P) until 4 glucosyl remain
• Resulting structure = limit dextrin

Question 17

What are the 2 debranching enzyme activities?

Answer 17

1) Oligo-alpha(1->4)->alpha(1->4)-glucantransferase removes the outer 3 of 4, transfer to nonreducing end
- functions as 4:4 transferase because alpha(1->4) bond is broken and alpha (1->4) bond is made
2) Remaining glucose residue attached in alpha (1->6) is removed hydrolytically by amylo-alpha(1->6)-glucosidase activity, releasing free glucose

Question 18

Glucose 1-phosphate is converted to what? By what and where?

Answer 18

To glucose 6-phosphate; in cytosol by phosphoglucomutase
-Liver: G-6-P transported into ER by glucose-6-phosphate translocase and converted to glucose by glucose 6-phosphatase (only organ that can do this)

Question 19

What is alpha(1->4)-glucosidase?

Answer 19

Lysosomal enzyme that continuously degrades a small amount of glycogen (1-3%)
-purpose of this pathway is unknown

Question 20

What does deficieny of alpha(1->4)-glucosidase cause?

Answer 20

Accumulation of glycogen in vacuoles in lysosomes, resulting in the serious glycogen storage disease (GSD) Type II: Pompe disease

Question 21

Regulation of glycogenesis and glycogenolysis occurs on what 2 levels?

Answer 21

1) Glycogen synthase and glycogen phosphorylase are hormonally regulated (by phosphorylation/dephosphorylation)
- Insulin and glucagon
2) Allosterically regulated