Glycogen metabolism

Question 1

UDP-glucose pyrophosphorylase

Answer 1

glucose-1-phosphate + UTP –> UDP-glucose + PPi ∆G=0Kj/mol
coupled with: H2O + PPi (inorganic pyrophosphatase) –> 2Pi ∆G=-33Kj/mol

1st step glycogen synthesis

Question 2

glycogen synthase

Answer 2

UDP-Glucose + glycogen (N residues) –> UDP + Glycogen (N+1)

Inhibited by physiological level of ATP, ADP and Pi and by phosphorylation

G6P facilitates dephosphorylation of glycogen syntase-b

Question 3

Amylo-(1,4-1,6)-transglycosylase

Answer 3

• Transfer of 7 glycosyl (must come from an 11chain residue) residue to a C6-OH
• New branch point must be 4 residues away from another branch point

Question 4

Overall reaction for synthesis of glycogen

Answer 4

Glucose + 2ATP + (glycogen, N) + H2O –> (Glycogen n+1) + 2ADP + 2Pi

Question 5

Degradation of glycogen

Answer 5

1) Generation of glucose-1-phosphate
2) Debranching
3) Conversion of Glucose-1-phosphate to glucose-6 phosphate

Question 6

Glycogen phosphorylase

Answer 6

Glycogen (N) + Pi –> Glycogen (N-1) + Glucose-1-phosphate

• works 5 units away form branch point
• 1st step glycogen degradation

-Phosphorylase b (R-form/active) –> phosphorylase b (T form/inactive) +ATP Phoshorylase a-2P (Tform/inactive) –> Phosphorylase-a-2P (Rform/active)

Phosphorylase b: Rform –> Tform (presence of ATP and/or G6P)
Tform –> Rform (presence of AMP)
- phosphorylase a: R form –> T form (high glucose)

Question 7

å(1-4) glycosyl transferase

Answer 7

Transfer 3 å(1-4) linked residues to the non-reducing end of another branch (5units away from branch point).
What will be left is one glycosyl (1-6) linked molecule).
-2nd reaction in glycogen degradation

Question 8

å(1-6) glucosidase

Answer 8

Remaining glycosyl of the branch point is hydrolyzed into glucose. (8% converted into glucose)

Question 9

Phosphoglucomutase

Answer 9

glucose-1-phosphate glucose-1,6-bisphosphatase glucose-6-phosphate –≥ glyocolysis

Question 10

Phosphorylase kinase

Answer 10

phosphorylates: Glycogen phosphorylase (active) and Glycogen synthase (inactive)

phosphorylase kinase b: active when elevated [Ca]
Phosphorylase kinase a: active even at low [Ca]

Subtypes:
å and ß: gets phosphorylates
∂: calmodulin (CaM), calcium sensitivity
y: catalytic subunit

Active: 1) phosphorylation of phosphorylase kinase-b to phosphorylase kinase a (via cAMP)
2) activation of phosphorylase kinase-b through elevated [Ca] (neural)

Question 11

Protein kinase A

Answer 11

phosphorylates: Phosphorylase kinase (active), Glycogen synthase (inactive), Phosphoprotein phosphatase inhibitor (active).
Extra phosphorylation of Gm subunit –> decreased affinity of PP1c.
R2C2 PKA + 4cAMP 2C PKA + R24cAMP.

Question 12

PIP2 intracelular signaling

Answer 12

epinephrine binding to alpha-adreno receptors –> activation PLC –> hydrolysis of PIP2 into IP3 and DAG,
IP3–> open Ça channels –> activation of b-phosphorylase kinase and PKC –> phosphorylation of glycogen phosphorylase and glycogen synthase.

DAG –> activation of PKC –> inhibition of glycogen synthase.

Question 13

Synthesis of glycogen

Answer 13

1) Synthesis of UDP-glucose
2) elongation of a pre-existing glycogen chain using glucose
3) creation of new 1,6-glucosyl branch points.