Glycogen Metabolism II Flashcards
What are the two key enzymes of glycogen metabolism?
glycogen synthase and glycogen phosphorylase
Glycogen synthase is activated in which form? deactivated in which from?
Active: non-phosphorylated “a” form
Inactive: phosphorylated “B” form
This kinase is responsible for activating glycogen synthase? It is under the control of what?
glycogen synthase kinase (GSK)
Insulin and PKA
The allosteric regulator of glycogen synthase is what?
gluc-6-phosphate (powerful activator)
Glycogen phosphorylase is active in which form? inactive in which form?
Active: relaxed “R” state in liver
Inactive: tense “T” state in muscle
Why are liver and muscle GP called isozymes?
they are products of separate genes and differ in their sensitivities to regulatory molecules
Mutation in liver GP causes?
Hers disease
Mutation in muscle GP causes?
McArdle syndrome
Liver GP is normally in active form, what inactivates it?
glucose; by binding to active sites.
Muscle GP is normally in inactive form. How is it activated?
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
Glycogenesis is favored in which state?
fed state
Glycogenolysis is favored in which state?
fasting state
Glycogenolysis is favored during what?
exercise.
How does insulin regulate glycogen metabolism?
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
What is normal blood glucose critera? What is prediabetic? what is diabetic?
normal 70-100 mg/dL (fasting), <140 fed
risk 100-125 fasting, >140 fed
diabetes >126 fasting >200 fed
Low blood sugar levels release glucagon. Muscle activity releases epinephrine. both of these hormones are mediated by what kind of receptors?
G protein coupled
Both hormones signal glycogen breakdown
Phosphorylation is carried out by?
phosphorylase kinase
activated by 2 ATP ->2ADP
Walk through regulation by glucagon.
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
what is the off switch to these pathways?
secretion of hormones stops.
_______ does not act on muscles?
glucagon
____ is the glucose sensor in liver cells?
Glycogen phosphorylase
SLIDE 27 has glycogen storage diseases. Learn them.
HIGH YIELD BOYS
GSD 0 is?
deficiency in glycogen synthase. must rely on glucose in diet. muscle cramps hypoglycemia must eat frequently
GSDIII/Cori Disease
deficiency in a-1,6,-glucosidase (debranching enzyme)
hypoglycemia and hepatomegaly
GSD IV/Andersen disease
deficiency in glucosyl (4:6) transferase (branching enzyme)
enlargement of liver and spleen
death by 5
GSD V/McArdle disease
deficiency in muscle glycogen phosphorylase
unable to supply muscles with glucose
weakness/cramps
exercise intolerance
myoglobinuria
GSD VI/Hers Disease
deficiency in liver glycogen phosphorylase
hepatomegaly (cannot breakdown glycogen in liver)
GSD II/Pompe Disease
defect in acid maltase
accumulation of glycogen in lysosomes
disrupts muscle and liver cells
progressive muscle weakness and myopathy
Enzyme replacement therapy
for GSD II.
Deliver recombinant human alpha-glucosidase via intravenous infusion
FDA approved. (myozyme and lumizyme, Genzyme corporation)
