L7- Glycogen Structure and Synthesis

Question 1

LO1: Glycogen structure vs function (bond types+significance of branching)

Answer 1

• branching allows easy deposit/mobilization of glucose (in fed vs. fasted states) because synthesis/degradation occur at the non-reducing ends (end of branch points)
• glycogen (polymer) structure does not cause osmotic force that could rupture the cell like glucose monomers would
• alpha-1,4 glycosidic bonds hold monomers within the chain together
• alpha-1,6 glycosidic bonds create the branch points

Question 2

LO2: Compare/contrast the functional roles of glycogen in muscle vs. liver

Answer 2

Muscle glycogen: energy reserve to be used during exercise; does not contribute to blood glucose

Liver glycogen: used to maintain glucose homeostasis; liver will store glucose as glycogen during fed state/degrade glycogen during fasted state

Question 3

LO3: Glycogen synthesis-reactions

Answer 3

1. trap blood glucose inside cytosol and convert it to an activated form (in muscle and liver)
2. conversion of glucose-6-phosphate to glucose-1-phosphate
3. formation of UDP-glucose (activated glucose-LO5)
4. transfer of glucose from UDP-glu to a non-reducing end of glycogen fragment
5. formation of alpha-1,6 glycosidic bonds to create branch points

Question 4

LO3: Glycogen synthesis- enzymes

hexokinase and glucokinase
phosphoglucomutase
UDP-glucose phosphorylase (LO5)
pyrophosphatases
glycogen synthase
oligo alpha-1,4-->alpha-1,6 glucan transferase

Answer 4

hexokinase and glucokinase: transfer phosphate group from ATP to the C6 hydroxyl group of glucose

phosphoglucomutase: converts glucose-6-phosphate to glucose-1-phosphate (mutases–>class of enzymes that move group from one position to another within same molecule)

UDP-glucose phosphorylase: catalyzes formation of UDP-glucose to “activate” glucose

pyrophosphotases: cleave high energy phosphate bonds to drive reaction forward

glycogen synthase: catalyzes transfer of UDP-glucose to non-reducing end (activated by dephosphorylation, or allosterically by glucose-6-P, which also can activate PP1)

oligo alpha-1,4–>alpha-1,6 glucan transferase: “branching enzyme”

Question 5

LO3: Glycogen synthesis- substrates/related proteins

Answer 5

ATP
Blood glucose
Glucose-1,6-bisphosphate (intermediate)
Glucose-1-phosphate
UTP
UDP-glucose
glycogen, partially degraded (primes glycogen synthesis)
glycogenin (acts as an acceptor of initial glucose residue if glycogen primer not available)

Question 6

LO4/LO5: what steps in glycogen synthesis require energy derived from hydrolysis of phosphate bonds?
*clarify in class

Answer 6

1. formation of UDP-glucose by UDP-glucose pyrophosphorylase (pyrophosphatases cleave the high energy phosphate bond to shift the equilibrium towards formation)
   * 2 phosphate bonds needed for each glucose monomer added to glycogen

Question 7

LO5: structure of “activated glucose”

Answer 7

glucose-1-phosphate and UTP are joined, with outer two phosphoryl residues of UTP getting cleaved

Question 8

LO6: cAMP regulation of glycogen synthesis

Answer 8

when cAMP is activated/high, glycogen synthase gets phosphorylated and becomes inactive–>blood glucose is high

• when glucagon is high compared to insulin
• when epinephrine is high
• cAMP activates PKA and inhibits PP1

when cAMP is not activated/low, glycogen synthase remains active (dephosphorylated)–>storage of glucose is promoted

• when insulin is high compared to glucagon
• cAMP can’t activate PKA and PP1 is no longer inhibited

Question 9

LO7: Describe the changes in glycogen synthase and the insulin/glucagon ratio with a high carbohydrate diet

Answer 9

1. In a high carb diet, there will be more glucose than needed to meet the energy needs of the cell so it will first be stored as glycogen, then when the physical capacity is reached/no more glycogenin molecules are available, the rest will be converted to fat for storage
2. Insulin is released in response to high blood glucose levels, and promotes dephosphorylation of glycogen synthase (to activate it; via PP1), thereby promoting fuel storage (glycogen synthesis)
3. Insulin works by activating protein phosphatase I (PP1), and decreasing levels of cAMP in the cell
4. When insulin increases, insulin/glucagon ratio increases
5. Insulin is antagonized by glucagon +epinephrine

Question 10

LO8: If someone had a deficiency in the branching enzyme, how would they respond to hypoglycemia and what type of dietary management plan would you suggest?

Answer 10

1. Without branching enzyme, glycogen structure would be abnormal (would have far fewer non-reducing ends)
2. Glucose wouldn’t be stored efficiently (due to space monomers take up/because there would be fewer branch points to act on)
3. Individual would effectively have little glycogen storage, so muscle wouldn’t be able to use glycogen stores for exercise and liver wouldn’t be able to maintain blood glucose levels
4. Individual would need constant supply of glucose through diet and may need to do a higher fat diet so that fats could be oxidized for energy (also excess glucose would be stored as glycogen and then not usable, so can’t have too much glucose)