Glycogen Metabolism II

Question 1

What are the two key enzymes of glycogen metabolism?

Answer 1

glycogen synthase and glycogen phosphorylase

Question 2

Glycogen synthase is activated in which form? deactivated in which from?

Answer 2

Active: non-phosphorylated “a” form
Inactive: phosphorylated “B” form

Question 3

This kinase is responsible for activating glycogen synthase? It is under the control of what?

Answer 3

glycogen synthase kinase (GSK)

Insulin and PKA

Question 4

The allosteric regulator of glycogen synthase is what?

Answer 4

gluc-6-phosphate (powerful activator)

Question 5

Glycogen phosphorylase is active in which form? inactive in which form?

Answer 5

Active: relaxed “R” state in liver
Inactive: tense “T” state in muscle

Question 6

Why are liver and muscle GP called isozymes?

Answer 6

they are products of separate genes and differ in their sensitivities to regulatory molecules

Question 7

Mutation in liver GP causes?

Answer 7

Hers disease

Question 8

Mutation in muscle GP causes?

Answer 8

McArdle syndrome

Question 9

Liver GP is normally in active form, what inactivates it?

Answer 9

glucose; by binding to active sites.

Question 10

Muscle GP is normally in inactive form. How is it activated?

Answer 10

AMP binds to active sites and stabilizes conformation of b in the active R state.

AMP comes form ATP via myosin and adenylate kinase signaling GP to breakdown glycogen during muscle contraction

Question 11

Glycogenesis is favored in which state?

Answer 11

fed state

Question 12

Glycogenolysis is favored in which state?

Answer 12

fasting state

Question 13

Glycogenolysis is favored during what?

Answer 13

exercise.

Question 14

How does insulin regulate glycogen metabolism?

Answer 14

High blood glucose causes a release of insulin by beta cells in the pancreas

Insulin binds to its receptor tyrosine kinase

this causes the activation of PKB

Leads to translocation of GLUT4 to membrane

PKB phosphorylates PP1* and GSK3

PP1* dephosphorylates glycogen synthase* and dephosphorylates glycogen phosphorylase

Net result is glycogen synthesis via activation of glycogen synthase and inactivation of glycogen phosphorylase

Question 15

What is normal blood glucose critera? What is prediabetic? what is diabetic?

Answer 15

normal 70-100 mg/dL (fasting), <140 fed
risk 100-125 fasting, >140 fed
diabetes >126 fasting >200 fed

Question 16

Low blood sugar levels release glucagon. Muscle activity releases epinephrine. both of these hormones are mediated by what kind of receptors?

Answer 16

G protein coupled

Both hormones signal glycogen breakdown

Question 17

Phosphorylation is carried out by?

Answer 17

phosphorylase kinase

activated by 2 ATP ->2ADP

Question 18

Walk through regulation by glucagon.

Answer 18

Low blood glucose levels cause alpha cells of the pancreas to release glucagon

bind of glucagon to its GPCR turns on G protein

Activates AC which forms cAMP

activates PKA

PKA phosphorylates glycogen synthase (inactivation)

PKA phosphorylates PK (activates)

PKA phosphorylates an inhibitor which inactivates PP1

Active PK phosphorylates glycogen phosphorylase (activation)

Net - glycogen breakdown via activation of glycogen phosphorylase

Question 19

what is the off switch to these pathways?

Answer 19

secretion of hormones stops.

Question 20

_______ does not act on muscles?

Answer 20

glucagon

Question 21

____ is the glucose sensor in liver cells?

Answer 21

Glycogen phosphorylase

Question 22

SLIDE 27 has glycogen storage diseases. Learn them.

Answer 22

HIGH YIELD BOYS

Question 23

GSD 0 is?

Answer 23

deficiency in glycogen synthase.
must rely on glucose in diet. 
muscle cramps 
hypoglycemia
must eat frequently

Question 24

GSDIII/Cori Disease

Answer 24

deficiency in a-1,6,-glucosidase (debranching enzyme)

hypoglycemia and hepatomegaly

Question 25

GSD IV/Andersen disease

Answer 25

deficiency in glucosyl (4:6) transferase (branching enzyme) enlargement of liver and spleen death by 5

Question 26

GSD V/McArdle disease

Answer 26

deficiency in muscle glycogen phosphorylase unable to supply muscles with glucose weakness/cramps exercise intolerance myoglobinuria

Question 27

GSD VI/Hers Disease

Answer 27

deficiency in liver glycogen phosphorylase hepatomegaly (cannot breakdown glycogen in liver)

Question 28

GSD II/Pompe Disease

Answer 28

defect in acid maltase accumulation of glycogen in lysosomes disrupts muscle and liver cells progressive muscle weakness and myopathy

Question 29

Enzyme replacement therapy

Answer 29

for GSD II. Deliver recombinant human alpha-glucosidase via intravenous infusion FDA approved. (myozyme and lumizyme, Genzyme corporation)