Lecture 18: Glycogen Metabolsim Regulation

Question 1

glucagon signaling stimulated by

Answer 1

low blood glucose levels

activates glycogen phosphorylase activity in liver cells (inc rates of glucose export)

Question 2

insulin signaling stimulated by

Answer 2

high blood glucose levels

activates glycogen synthase to store extra dietary glucose as glycogen in muscle cells

Question 3

Net phosphorylation through glucagon signaling leads to

Answer 3

glycogen degredation

Question 4

Net dephosphorylation through insulin signaling leads to

Answer 4

glycogen synthesis

Question 5

Hormone signaling

Answer 5

insulin and glucagon

SUSTAIN reciprocal regulation (very slow)

Question 6

allosteric regulators

Answer 6

AMP, glucose

QUICKLY control glycogen phosphorylase activity

Question 7

regulation of phosphorylase activity

Answer 7

T and R state

regulated by covalent mod (phosphorylation–conf change) and allosteric control (nrg charge)

Question 8

hormone regulation of glycogen phosphorylase

Answer 8

phosphorylation due to glucagon sig: shift to R state conf (active)
dephosphorylation due to insulin: shift to T state conf (inactive)

Question 9

Why does it make sense that glucagon stimulates glycogen phosphorylase activity, whereas insulin inhibits glycogen phosphorylase activity

Answer 9

depends on blood glucose levels: insulin leads to storage, glucagon leads to making glucose
need to be able to turn on/off protein at right time
glucagon is released in response to low blood glucose

Question 10

difference between regulation of phosporylase kinase in liver and muscle

Answer 10

liver: glucagon and epinephrine
muscle: just epinephrine
insulin in both

Question 11

regulation of muscle glycogen phosphorylase

Answer 11

Covalent through hormone: epinephrine and insulin signaling (phosphorylate)

insulin turns off
epi turns on
(otherwise same as in liver, just epi instead of glucagon)

T state of muscle can be shifted to R state by AMP binding without hormone: ALLOSTERIC REG (not phosphorylated tho). Same happens with ATP in reverse… go from R to T state w/o phosphorylation

Question 12

Why does AMP shift the unphosphorylated T state into the R state, why doesnt cell just wait for GLUCAGON signaling to take effect

Answer 12

also GLUCAGON does NOT act in muscles….. derp

Question 13

Why does AMP shift the unphosphorylated T state into the R state, why doesnt cell just wait for HORMONE signaling to take effect

Answer 13

its FASTER
cells need to be able to regulate whats going on very quickly, and hormone reg is slooooooow
we need to release glucose NOW

AMP shift is allosteric?

Question 14

Regulation of Liver glycogen phosphorylase

Answer 14

covalent mod through hormone signaling (gluc, epi, insulin) (DE)PHOSPHORYLATION

allosteric: when glucose conc incs, binding of glucose to the phosphorylase causes conf change to phosphorylated T state–> inactivates protein (it becomes good substrate to phosphotase) release of all to make unphosphorylated state
bind glucose to allosteric site
can shut down without dephosphorylation

Question 15

Why does glucose shift the phosphorylated R state into the T state, why not just “wait” for insulin signaling

Answer 15

its faster
if you have a lot of glucose in the blood, you shouldn’t be releasing more, you should shut it down

shut it down by glucose binding to the allosteric site
hormones can turn back on as needed

Question 16

Listen to slide 12 again

Answer 16

Listen to slide 12 again

Question 17

regulation of glycogen synthase activity

Answer 17

reciprocal regulation 
R state (active) dephosphorylated
T state (inactive) poshporylated

Question 18

R state of glycogen synthase

Answer 18

hydroxyl groups

multiple phosphorylation sites

Question 19

insulin and glycogen synthase

Answer 19

phosphotase bindig: turns it on HORMONAL

Question 20

G6P and glycogen synthase

Answer 20

(no insulin)

causes dephosphorylation ALLOSTERIC

Question 21

Why does it make sense that glucagon inhibits glycogen synthase activity

Answer 21

we see glucagon when blood glucose is low. we want to break down glycogen

we see insulin when blood glucose levles are high, so we want to make glycogen.

Question 22

why is glycogen synthase activity reciprocally regulated?

Answer 22

there is differential regulation of the two proteins

Question 23

hormone signaling in liver cells

Answer 23

net phosphorylation drives glycogen degen
net dephosphorylation drives glycgen synth
sustain reciprocal regulation

Question 24

allosteric regulators

Answer 24

AMP and glucose

quickly control glycogen phosphorylase activity

Question 25

Glycogen storage diseases: Von Gierke’s Disease

Answer 25

deficiency in enzyme glucose-6-phosphate

causes build-up of glycogen in liver b/c g6P accumulates and activates glycogen synth

Question 26

Glycogen storage diseases: McArdle’s Disease

Answer 26

defects in muscle glycogen phosphorylase

suffer from excercise-induced muscle pain b/c of inability to degrade muscle glycogen

Question 27

Pompe’s disease

Answer 27

due to deficiency in lysomal alpha 1,4 glucosidase
leads to build up of glycogen in the lysosomes
muscle and nerve damage result in short lifespan

treatment: just to infuse recombinant copy of enzymes into blood