GS regulation, allosteric and PKA/PP1c

Question 1

GS forms

Answer 1

2 enzymatically interconvertible forms. Overhang diagram
modified (m, phospho) , inactive form = b form
original (o; dephospho), active = a form.

Up to 9 ser per subunit that can be +/- Pi by several kinases ( such as PKA)

Question 2

insulin

Answer 2

activates GS by inhibiting GSK3, which would have phosphorylated GS (so if inhibit GSK3 cant go from o to m)

Question 3

AMPK

Answer 3

responsive to amount of AMP vs ATP

Question 4

GS regulated how

Answer 4

allosterically
if G6P binds to m-b-T , will cause m-b-T to change to m-a-R. At some point PP1c will remove the phosphates. So causes conf change so that phosphates can be removed. Similar to Gluc+G6P to cause conf change in GP so that its phosphates are exposed.

Also regulated by intracellular location.

G6P is the allosteric effector.

Question 5

activating m-b

Answer 5

depends on allosteric activation by G6P. G6P will override inhibution of +Pi and G6P binding will cause change in conf of m-GS -b. Enables easier -Pi by phosphatases like PP1c.

Question 6

GS cascade

Answer 6

bicyclic boxes, in yellow PKA can act directly on GS, so has 1 less reg stage than phosphorylase as PKA is directly affecting.

Question 7

Result of regulation of GS

Answer 7

breakdown has greater sensitivity in regulation. But there are still hurdles to store the glycogen. thixs is good because stored glucose is an important asset, so want to make sure you are really needing to use it.

Question 8

tetrameric conf system

Answer 8

G6P binds at subunit interface, so Arg 583 and Arg 587 will ion pair with Pi, which anchors G6P so that its sugar ring H-bonds with His and Gln.

This will cause a reordering of the AA so that Asparagine can hydrogen bond across dimeric interface which is the DRIVER of trhe conf change. Reordering to allow for access of activation site in R state