glycogen metabolism Flashcards
what enzyme removes a G-1-P from glycogen?
in what state does it do this (active/inactive)
glycogen phosphorylase a
active
what converts glycogen phosphorylase a to glycogen phosphorylase b, inactivating it
protein phosphatase 1G
(and glucose-6-phosphate)
dephosphorylation reaction
what converts glycogen phosphorylase b to glycogen phosphorylase a, activating it
phosphorylase kinase a
what converts phosphorylase kinase b to a, activating it?
PKA
what increases intracellular PKA levels?
glucagon and adrenaline via the cAMP cascade
what enzyme catalyses the addition of G-1-P to glycogen?
glycogen synthase a
(active)
what converts glycogen synthase a to glycogen synthase b, inactivating it?
GSK3 (glycogen synthase kinase 3)
phosphorylation reaction
what converts GSK3-P to its active form GSK3?
PKB
what converts glycogen synthase b to a, activating it?
protein phosphatase 1G
what inhibits protein phosphatase 1G?
protein phosphatase inhibitor-1
PPI1 activated by PKA
how is protein phosphatase inhibitor-1 inactivated?
phosphorylation by protein phosphatase-2A
what are the biochemical effects of insulin on the balance of glycogenesis to glycogenolysis
- PI3 cascade, activates PKB, inactivates GSK3, stops conversion of glycogen synthase a to b (activates)
- activates protein phosphatase 1G, promotes conversion of glycogen synthase b to a (activates)
- activates protein phosphatase 1G, promotes conversion of glycogen phosphorylase a to b (inactivates)
overall promotes conversion of glucose to glycogen
what are the biochemical effects of cAMP (causes by glucagon/adrenaline secretion) on the balance of glycogenesis to glycogenolysis
- activates PKA, activates phosphorylase kinase, activates glycogen phosphorylase a
- activates PKA to convert PP1G into a low activity form, therefore glycogen synthase b is not converted to a
overall the breakdown of glycogen is promoted - activates PKA to phosphorylate sites 1 and 2 of regulatory subunit 1G to inactivate PP1 as above during the adrenaline-induced emergency, but immediately dephosphorylates site 2 after adrenaline stops so that PP1 can activate glycogen synthase to replenish stores
which hormones stimulate glycogenolysis in the liver
glucagon and adrenaline
which hormone stimulates glycogenolysis in the muscles
just adrenaline
(do not have receptors for glucagon)
how much adrenaline is needed to mobilise enough glucose to use as respiratory fuel?
nanomolar amounts
what happens when adrenaline docks to its receptor in muscle?
signal transduced through G protein, adenylyl cyclase, ATP -> cAMP, activates PKA
what are the metabolic opponents of PKA
protein phosphatases
how does cAMP activate PKA?
when inactive, PKA is a tetramer of 2 catalytic and 2 regulatory subunits
cAMP binds the 2 regulatory units and liberates the active subunits
how is protein phosphatase-1 inactivated?
PKA phosphorylates site 2 of regulatory subunit of protein phosphatase-1G complex
protein phosphatase 1 dissociates from the complex
is now vulnerable to attack from protein phosphatase inhibitor 1
PPI1 has to be activated by phosphorylation by PKA
it is deactivated at rest by protein phosphatase 2A
where is glycogen phosphorylase b phosphorylated to form a?
serine at N-14 by phosphorylase kinase
what state is phosphorylase b in in resting muscle?
inactive, T form
what is the effect of AMP on phosphorylase b?
stimulates it by forming R form which has higher affinity for phosphate
what molecules counter the effect of AMP on phosphorylase b?
ATP and G-6-P
phosphorylase b returns to T form
when is glycogenesis most active and why?
in the fed state as insulin is needed to transport glucose into muscle cells
what is the action of insulin that counteracts the production of cAMP by glucagon/adrenaline?
an insulin-stimulates series of reactions leading to actiavtion of cAMP phosphodiesterase 3B and conversion of cAMP to AMP
what chemicals lead to the occurrence of glycogen synthesis?
protein phosphatase 1 and 2A
what 6 things determine whether glucose is stored or used in glycolysis?
- cell energy needs
- glucose availability
- hormonal regulation
- enzyme regulation
- cell signalling
- tissue specificity
