Kerry Loomes-2 Flashcards
How is Glucose-6P converted to Glucose-1P?
Through a reversible reaction by phosphoglucomutase
What are the features of insulin?
Produced by the islets beta cells of the pancreas
Secretion by high blood glucose results in glucose to be taken up from the circulation and converted to glycogen in the liver and muscle
What are the features of glucagon?
Produced by islet alpha cells of the pancreas
Its secretion in response to low blood glucose results in glycogen breakdown in liver to produce glucose that enters the circulation
Does not act on muscle
What controls glycogen metabolism?
The amount of phosphorylation on glycogen synthase and glycogen phosphorylase
How is glycogen phosphorylase regulated?
Glycogen phosphorylase can be either phosphorylated (a form) or unphosphorylated ( b form) controlled by phosphorylase kinase which is itself regulated by hormones
The phosphorylated form is active
It also has an R and T state with both a and b forms being able to convert between these states
R is active T is inactive
b-form moves to T in response to ATP and or Glucose-6P or moves to R in response to AMP
a- form moves to T in response to glucose
The T form can be inter-converted between b and a but not the R form
What is the role of glycogen phosphorylase in glycogen metabolism?
It breaks down glycogen to glucose-1P
What is the mechanism of action of phosphorylase kinase?
Transfers terminal phosphate of an ATP onto a protein to activate glycogen phosphorylase
What is the function of protein phosphatase-1?
This inactivates glycogen phosphorylase and activates glycogen synthase by removing phosphate groups from both proteins
How is the activity of glycogen synthase regulated?
Glycogen synthase is active if it is not phosphorylated, phosphorylation can occur at 9 serine sites
Glycogen Synthase Kinase is constitutively active and adds phosphates to glycogen synthase
Protein Kinase A which is hormonally regulated also phosphorylates glycogen synthase
Other Kinases are Phosphorylase kinase and Casein Kinases 1 and 2
Phosphates are removed by protein phosphatase-1 which is hormonally regulated
How does glucagon and epinephrine regulate glycogen breakdown?
They activate adenylate kinase which produces cAMP which will activate protein kinase A by binding to the two regulatory subunits
Protein kinase A then phosphorylates Glycogen synthase to down regulate its activity while also phosphorylating the alpha and beta monomers phosphorylase kinase to produce a weakly active form (which can be made very active through the addition of a Ca2+ to the sigma monomers)
Protein Kinase A activates protein phosphatase-1 inhibitor preventing the removal of phosphate groups from glycogen phosphorylase so it can remain in the active form
What is the affect of insulin?
Uses phosphodiesterase 3B to produce AMP from cAMP
What is the structure of protein phosphatase-1
PP-1 is the major active form and associated with glycogen via the regulatory PP-1G unit
Phosphorylation of one site activates PP1 while phosphorylation of two sites inactivates the proteins
How is PP1-G regulated?
It can be phosphorylated by insulin to be activated
PP-2A can then remove this phosphate to turn PP-1 off
Alternatively Protein Kinase A can also phosphorylate site 2 causing the PP-1 and PP-1G to dissociate preventing PP-1 function
