LECTURE 8 - GLYCOGEN 3 Flashcards
how does the insulin signaling pathway work
- insulin binds to receptor tyrosine kinase
- the receptor tyrosine kinase autophosphorylates itself
- this turns on protein kinases
- these protein kinase turn off glycogen synthase kinase
- glycogen synthase kinase turns off glycogen synthase
- but since there is no inhibitor of glycogen synthase, it can be turned on by PP1 to activate glycogen synthesis
the insulin pathway turns off an inhibitor=activation
how does the Gas pathway work?
- epinephrine (muscle) or glucagon (liver) binds to the receptor
- the receptor is a G protein coupled receptor (GPCR) made of 7 transmembrane units, it has pockets for the ligand
- there is a change in conformation which will transmit a signal to GDP alpha subunit, attached to beta and gamma (heterotrimeric complex)
- when the ligand binds to the GPCR, GDP is now GTP, and the beta and gamma units dissociate
- this activates adenylate cyclase, which is only active with GTP bound to it
- adenylate cyclase produces cAMP from ATP
- the cAMP allosterically activates PKA
- PKA activates phosphorylase kinase (the 16 unit one)
- phosphorylase kinase activates glycogen phosphorylase, which chops off glucose off glycogen to make G1P
what is PIP2 cut into?
DAG and IP3
how does the Gaq pathway work?
- the ligand binds to a GPCR protein on the cell membrane
- this activates the heterotrimeric GDP complex, and beta and gamma dissociate again
- GTP activates phospholipase C
- phospholipase C hydrolyses PIP2 into DAG and IP3
- IP3 stimulates stimulates the release of calcium from the ER, which activates various cellular processes through calmodulin
- DAG activates protein kinase C, which also modulates several cellular processes (inhibits glycogen synthase)
summary of the hormone receptors involved in glycogen control
map of hormonal control of glycogen metabolism
how does muscle contraction work?
what happens to glycogen in the muscle upon stress or upon contrcation?
- epinephrine binds to the beta adrenergic receptor
- this increases cAMP, which causes muscle contraction, which increases Ca2+
- this activates PKA, which inhibits glycogen synthase, phosphorylates PP1c inhibitor and GM
- this activates phosphorylase kinase
- phosphorylase kinase activates glycogen phosphorylase and inhibits glycogen synthase
- PP1c dissociates from GM and binds to its inhibitor, PP1c is inhibited
- glycogen breakdown is on and synthesis is off
what happens to glycogen in the muscle after a meal?
- high blood glucose and high blood isulin
- insulin stimulates glucose uptake via GLUT4, which activate insulin stimulated protein kinase
- insulin stimulated protein kinase activates PP1c through association with GM
- active PP1c dephosphorylates glycogen synthase adn inactivates phosohorylase kinase
- high G6P activates glycogen synthase
- inactive phosphorylase kinase activates glycogen synthase
- glycogen breakdown is off and glycogen synthesis is on
what is the deficiency in von Gierke’s Disease and the consequence?
deficiency in glucose 6 phosphatase which catalyses the final step to release glucose into bloodstream
this leads to accumulation of glycogen in normal structure, but inability to increase blood glucose levels in response to hormones
symptoms:
massive liver enlargement
hypoglycemia and failure to thrive, cannot give glucose to organs
the treatment is to reroute the portal vein away from the liver
what is McArdle’s Disease
deficiency in phosphorylase which catalyses glycogen breakdown to G1P
glycogen breakdown is impaired: reduced fuel for glycolysis to keep up with demands
symptoms: painful cramps during exercise
elevated ADP levels during exercise
there is not mechanism to make ATP
what is Hers’ Disease?
liver phosphorylase deficiency
catalyses glycogen breakdown to G1P
leads to inability to breakdown glycogen in liver
symptoms ar hypoglycemia since glycogen phosphorylase cannot respond to the need for glucose production by the liver
what is the cori cycle
