Lecture 3 Flashcards
Describe the structure of glycogen
linear alpha-1,4-glycosidic bonds with alpha-1,6-glycosidic branches
Glycogen is _______, this means there are more ends for enzyme action to rapidly add and release glucose
Dendromeric
Which enzyme regulates glycogen synthesis?
Glycogen synthase
Which enzyme regulates glycogen breakdown?
Glycogen phosphorylase
True or false: glycogen synthase makes alpha-1,6-glycosidic bonds between glucose moieties?
False: GS makes the alpha-1,4-linkages
Describe the steps leading to the formation of glycogen from glucose (4 steps)
(1) glucose is phosphorylated at position 6 by glucokinase to give glucose-6-phosphate (traps glucose in the cell)
(2) G6P converted to G1P by phosphomutase
(3) G1P converted to UDP-glucose by UDP glucose pyrophosphorylase (first committed step of glycogenesis)
(4) Glycogen synthase forms alpha-1,4-glycosidic bonds between UDP-glucose moieties
How does glycogen phosphorylase reverse glycogen sytnhesis?
breaks alpha-1,4-glycosidic bonds releasing G1P
What are the different fates of G1P?
enter glycolysis (E.g. in muscles)
converted to glucose and exported (E.g. in liver cells)
Give one positive and one negative regulatory mechanisms of glycogen synthase?
Negative regulation: Glycogen synthase kinase 3 (GSK3β) phosphorylates and inhibits Glycogen synthase prevent glycogen synthesis
Positive regulation: protein phosphatase 1 removes inhibitory GSKβ to activate glycogen synthase
How is GSK3β action regulated?
phosphorylation of inhibitory ser9 by Akt/PKB in response to insulin signalling
What are the steps that result from insulin signalling on glycogenesis via glycogen synthase?
Insulin via PI3K activates Akt/PKB
Akt/PKB phosphorylates inhibitory Ser9 of GSK3β, inactivating it
GSK3β can no longer carry out inhibitory phosphorylation of glycogen synthase
Protein phosphatase 1 activates glycogen synthase by removing phosphate
Glycogen synthase is able synthesise glycogen to reduce blood glucose levels
Describe the structure of the GLUT4 glucose transporter?
12 transmembrane regions
intracellular N and C-terminals
Which cells use GLUT4 as part of insulin response?
Adipocytes and muscle cells
Which glucose transporter is present in hepatocytes?
GLUT2
Where are the GLUT4 transporters stored under basal conditions?
GLUT4 storage vesicles (GSVs)
Where are the GSVs located in the cell under basal conditions?
Majority located by the trans Golgi network (TGN) adjacent to the nucleus
Under no insulin signalling, what happens to GLUT4?
endocytosed
What are the steps of insulin signalling that lead to the exocytosis of GSVs and insertion of GLUT4 into PM?
TO FINISH…!!!!
Insulin signalling via PI3K activates Akt/PKB
Akt/PKB phosphorylates Akt substrate 160kDA (AS160) at 5 sites
Rab remains active in GTP-bound state
Insulin releases GLUT4 bound TUG
small GTPase RALA associated with the GSV facilitates transport of GSV via microtubules
MYO1C motor binds RALA to facilitate transport of GSV to PM via actin filaments
TO FINISH ……
