Liver Glycogen Metabolism Flashcards
what’s the importance of storing glycogen?
maintaining blood sugar. the liver breaks down glycogen to export glucose to cells that need it (i.e. RBCs and brain cells)
describe the structure of glycogen
polysaccharide
highly branched polymer of glucose
mostly alpha-1,4 glycosidic linkages with alpha-1,6 glycosidic linkages at the beginnings of a branch
what tissues store significant amounts of glycogen?
muscle cells and liver cells
muscle cells use glycogen for fuel while liver cells do not. liver cells break down glycogen for glucose to maintain blood sugar. muscle cells can use glycogen as fuel even in anaerobic conditions
define glycogenolysis
glycogen breeakdown
define glycogenesis
glycogen synthesis
explain why it is beneficial for glucagon signals to stimulate both glycogenolysis and gluconeogenesis
both add sugar to the blood
name the enzyme that allows liver cells to convert glucose-6-phosphate —> glucose.
why is this enzyme needed for raising blood sugar?
glucose-6-phosphatase
necessary for liver glycogen to end up as blood sugar; once the phosphate is removed, the glucose is exportable
location of glucose-6-phosphatase
endoplasmic reticulum
name the enzyme:
glucose-1-phosphate <—–> glucose-6-phosphate
when would it go each direction?
phosphoglucomutase
in fasting state or during exercise (glycogenolysis), it goes the direction from G1P –> G6P
in glycogenesis, goes the direction where G6P —> G1P
donor of glucose rings to variety of building products, including addition of glucose rings to ends of branches of growing glycogen molecule in glycogenesis
UDP-glucose
name enzyme that phosphorylates glucose in muscle cells
hexokinase
name enzyme that phosphorylates glucose in liver cells
glucokinase
describe the rxn that forms UDP-glucose
glucose-1-phosphate reacts with UTP to produce pyrophosphate and UDP-glucose
name the enzyme that makes a pre-existing glycogen molecule bigger by one glucose ring
who’s the donor?
what’s the product?
glycogen synthase
UDP-glucose
UDP is a product
what type of linkages does glycogen synthase produce?
alpha-1,4 linkages
what enzyme helps to create branching in glycogen molecules by adding alpha-1,6 glycosidic linkages?
branching enzyme or 4:6 transferase
- does NOT use UDP-glucose
- does NOT make glycogen molecule any bigger, only restructures it
what enzyme breaks an alpha-1,4 linkage at the end of a branch to remove a glucose ring?
glycogen phosphorylase
what type of rxn is the glycogen phosphorylase rxn?
phosphorylysis rxn
uses a Pi instead of water to break the alpha 1,4 linkage
product in the glycogen phosphorylase rxn
glucose-1-phosphate
what enzyme breaks down the alpha-1,6 linkages in glycogen?
what type of rxn is this
debrancher enzyme
hydrolysis rxn
- water goes in, breaking the alpha 1,6 linkage and releasing a small amount of glucose (bare naked glucose)
what enzyme breaks an alpha 1,4 linkage and then will reattach the shortchain of glucoses, forming a 1,4 linkage elsewhere
4:4 transferase
what enzyme catalyzes hydrolysis of 1,6 linkage in glycogen molecule, leavingone molecule of bare naked glucose?
alpha 1,6 glucosidase
catalytic cofactor that resides in the active site of glycogen phosphorylase
pyridoxal phosphate (PLP), from vitamin B6 (pyrodoxin)
predict effect of insulin signals on glycogenesis and glycogenolysis
speed up glycogenesis
slow down glycogenolysis
insulin stimulates glycogensis after a high carb meal
predict the effect of glucagon signals on glycogenesis and glycogenolysis
slow down glycogenesis
speed up glycogenolysis
in the fasting state, we want the liver to break down glycogen until we eat again to maintain blood. sugar. glucagon is the hormone for stimulating glycogenolysis in the liver during the fasting state
predict the effect of epinephrine on glycogenesis and glycogenolysis
slow down glycogenesis
speed up glycogenolysis
during exercise, we breakdown glycogen in for muscle cell use as energy. the hormone for this is epinephrine. this means glygogenolysis would speed up
predict the effects of an increase in cytosolic level of cAMP
glucagon signals and epinephrine signals can increase levels of cAMP in cytosol, speeding up glycogenolysis
predict the effects of an increase in cytosolic level of calcium ion
in muscle cells, cytosolic calcium increases because of AP traveling down t-tubules causing calcium to stream out of the sarcoplasmic reticulum into the cytosol
some of that calcium helps with muscle contraction by binding troponin C
other calcium helps break down glycogen for fuel
this speeds up glycogenolysis
calcium also activates phosphorylase kinase
effect of phosphorylating glycogen synthase
inactivates it
effect of phosphorylating glycogen phosphorylase
activates it
when would we want both glycogen synthase and glycogen phosphorylase to be phosphorylated?
what causes both enzymes to be phosphorylated?
when glycogenolysis is desirable because this will activate glycogen phosphorylase and inactivate glycogen synthase
glucagon signals in the fasting state and/or epinephrine during exercise causes this
what enzymes can catalyze phosphorylation of glycogen synthase
a variety of enzymes (including phosphorylase kinase)
what catalyzes phosphorylation of glycogen phosphorylase
phosphorylase kinase ONLY
what enzyme catalyzes desphosphorylation of glycogen synthase and glycogen phosphorylase
what is the effect?
what hormone makes this happen?
protein phosphatase
- hydrolysis of phosphoester bond
glycogen synthase is active
glycogen phosphorylase is inactive
speeds up glycogenesis
insulin in the fasting state
explain how glucagon receptors lead to increase glucose in the blood
glucagon receptors are heptahelical, heterotrimeric G-protein coupled.
- glucagon binds to heterotrimeric receptor
- receptor changes shape
- heterotrimeric g protein changes shape
- alpha subunit drops GDP and picks up GTP
- shape change activates adenylate cyclase
- cAMP concentration increases, becomes second messenger
- protein kinase A get activated which catalyzes phosphorylation of both phosphorylase kinase (activating it) & glycogen synthase (inactivating)
- catalyzes the breakdown glycogen (glycogenolysis)
- formation of glucose-1-phosphate that can become glucose-6-phosphate by phosphoglucomutase
- glucose-6-phosphatase rxn turns glucose-6-phosphate to glucose that can be exported to the blood
insulin signals lead to activation of a protein phosphatase called ______________
what happens next?
protein phosphatase 1 (PP1)
causes glycogen synthase to be dephosphorylated, making it active
UDP-glucose can then be used to make glycogen
enzymes that can be desphosphorylated by PP1
glycogen synthase glycogen phosphorylase (inhibits) phosphorylase kinase (inhibits)
what enzyme catalyzes the hydrolysis of cAMP —> AMP
what happens after this rxn occurs?
what hormone causes this?
cAMP phosphodiesterase
the effects:
protein kinase A won’t be activated anymore
insulin signals
effects of glucagon signals on cAMP
effect of insulin signals on cAMP
glucagon raises cAMP levels
insulin lowers cAMP levels
receptors for epinephrine are ___________ receptors
adrenergic
signal transduction mechanism for when epinephrine binds to a beta-adrenergic receptor of a liver cell
explain.
adenylate cyclase system
- epinephrine binds to heptahelical receptor of liver cell
- receptor changes shape.
- heterotrimeric G protein senses shape change
- alpha subunit drop GDP and picks up GTP
- adenylate cyclase activated
- cAMP concentration increases, becomes second messenger
- protein kinase A activated, catalyzing phosphorylation of glycogen synthase (turning off) and phosphorylase kinase which turns on glycogen phosphorylase for the breakdown of glycogen
increase in glycogenolysis
signal transduction when epinephrine binds to an alpha-1 adrenergic receptor of a liver cell
explain
phospholipase c.
- epinephrine binds to alpha-1 heptahelical receptor of a liver cell
- receptor changes shape.
- heterotrimeric G protein senses shape change
- alpha-subunit drops GDP and picks up a GTP
- activates phospholipase C (membrane-associated enzyme)
- breaks the membrane phospholipid molecule into two pieces that serve as second messengers (DAG & inositol triphosphate)
- IP3 receptors on the endoplasmic reticulum opens doors for calcium ion
- Ca2+ passively flows out of ER into cytosol
DAG and Ca2+ released from the ER activate several protein kinases (including phosphorylase kinase) - Ca2+ binds to calmodulin (direct allosteric activation of phosphorylase kinase)
- phosphorylase kinase catalyzes phosphorylation of glycogen phosphorylase & glycogen synthase
- glycogenolysis is sped up by epinephrine
