regulation of PP1 (PP1c) in the LIVER

Question 1

using pp1c so need…

Answer 1

a GL subunit to bind pp1 to glycogen

Question 2

m-phosphorylase a’s R and T forms

Answer 2

both strongly bind to GL in GL-PP1c system .

GP is marked by green circles (active) which become red square (inactive) sop there has been a conf change caused by Glucose+G6P summation.

Question 3

m-phosphorylase a’s R form

Answer 3

strong allosteric inhibition of PP1c, which is unusual bc its the protein doing the inhibition. The first time we saw this was HK-IV binding to flux

ser-14 buried at dimer interface, but if high gluc concentration PLUS high G6P, we get R to T (right wall of hut… m-a-T NO LONGER buried)… so Pi are no longer buried and now accessible for -Pi by PP1c meaning that pp1c will remove the phosphate groups. during this time GP also moves.

Question 4

GP m-a-T converts to o-b-T

Answer 4

GP will have low affinity for PP1c, so it moves, no lnger attached to pp1c. If it moves, it is no longer able to allosterically inhibiting PP1c. Allosteric inhibition stops (-Pi of phosphorylase m-a to o-b stops)

PP1c now active, can -Pi enzymes such as GS (b to a) to activate GS.

Question 5

in liver cells

Answer 5

10 more phosphorylase than PP1c, so cannot do the release of PP1c from GP until greater than 90% of phosphorylase in o-b form. This is useful because we are turning up usage of glucose storage by glycogen synthesis (have high BS trying to get rid of it), GP is breaking down Glyc to run glycolysis/increase BS. So this is telling us we are turning down usage by breakdown and turning up useage by storage.

So: we dont start storing glucose until levels are really high… When have lots of glucose you want this process to kick in.