Glycogen synthesis/ Glycogenolysis

Question 1

Glycogen

Answer 1

• major storage form of glucose in the cell
• 2 storage sites: muscle and liver
• branched polymers of glucoe
• new strand formed on a small protein: glycogenin
• each granule is ONE molecule
• alpha-1,4- linked glucose with alpha-1,6-linked branches

Question 2

Muscle glycogenolysis

Answer 2

• muscle cells don’t have glucose-6-phosphatase
• glucose is broken down into a phosphorylated form and since muscle cell can’t cleave off the phosphate, glucose cannot leave the muscle cell

Question 3

osmotic pressure of glycogen

Answer 3

it is one molecule thus it reduces the osmotic pressure of the glucose in the cell (thus the cells won’t absorb water and burst)

Question 4

glycogen phophorylase

Answer 4

• breaks bonds using Pi
• splits bond on the non-reducing end of the strand
• co factor of PLP (which is the source of the Pi)
• glucose-1-P is the major product
  (a single glucose is produced by the branching enzyme)

Question 5

Fate of glucose-1-phosphate

Answer 5

• converted reversibly to glucose-6-phosphate
• enzyme = phophoglucomutase
• cofactor of glucose-1,6-bisphophate
  Muscle: now uses glucose
  Liver; P is removed and glucose enters the blood

Question 6

UDP-glucose

Answer 6

• glucose is joined to adenosine by a phosphoanhydride bridge
• committed molecule to glycogen synthesis

Question 7

Biosynthesis of UDP-glucose

Answer 7

• pyrophosphorylase rxn is reversible by itself
• actually prefers the reverse rxn
• hence the name of the enzyme = NDP-sugar pyrophophorylase
• the pyrophosphate that is released is cleaved by inorganic pyrophophatase almost instantaneously which releases 8 kcal of energy and drives NDP-sugar synthesis

Question 8

Branching enzyme

Answer 8

• when the strand get to be 11 monomers from the nearest branch point:
• removes a chunk of 7 residues and adds it to the C6 of a glucose four residues away from the existing branch

Question 9

Trading off total energy for available energy

Answer 9

• glycolysis = net energy of 2 ATP
• stored glucose = net energy of 1 ATP
• this means storing glucose loses half it’s energy stores but it is worth it to have available energy for the cell

Question 10

Muscle: phosphorylase kinase

Answer 10

• needs to have Ca2+ present to be active
• if enzyme is already phosphorylated then it will be potentiated and be more efficient (due to adrenaline- ie hormonal regulation)

Question 11

Glycogen synthase

Answer 11

• makes glycogen
• active form: denoted “I” when unphophorylated
• inactive form: denoted “D” when phosphorylated
• after meal, G-6-P can bind to glycogen synthase D and activate it (enzyme is ligand dependent)

Question 12

Phosphorylase

Answer 12

• degrades glycogen
• active when phosphorylated by phophorylase kinase
• also activated by AMP without being phosphorylated (form of quick, efficient regulation in a single muscle without worrying about the whole body)

Question 13

Phosphoprotein phosphatase (PP-1)

Answer 13

• bound to phosphorylase a (inactive form)
• glucose enters cell and causes conformation change that cleaves of phosphate and PP-1
• PP-1 can now go de-phosphorylate other targets

Question 14

von Gierke’s

Answer 14

• glucose-6-phosphatase deficiency
• inhibition of glucose delivery to blood
• hypoglycemia (low blood sugar) –> resulting in buildup of AMP –> resulting in uric acid buildup

Question 15

Pompe’s disease

Answer 15

• deficiency of alpha-1,4-glucosidase
• lysosomal instead of cytosolic
• glycogen accumulates in the liver
• enlarged lysosome bursts emptying digetive enzymes into the cell and causes cell death and tissue disruption

Question 16

McArdle’s disease

Answer 16

• muscle glycogen phosphorylase deficiency
• can’t break down glycogen in muscle
• onset in adulthood usually
• inability of the muscle to use glycogen to regenerate ATP anaerobically