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Endocrine Biochem > Liver Glycogen Metabolism > Flashcards

Liver Glycogen Metabolism Flashcards

1
Q

what’s the importance of storing glycogen?

A

maintaining blood sugar. the liver breaks down glycogen to export glucose to cells that need it (i.e. RBCs and brain cells)

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2
Q

describe the structure of glycogen

A

polysaccharide
highly branched polymer of glucose
mostly alpha-1,4 glycosidic linkages with alpha-1,6 glycosidic linkages at the beginnings of a branch

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3
Q

what tissues store significant amounts of glycogen?

A

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

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4
Q

define glycogenolysis

A

glycogen breeakdown

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5
Q

define glycogenesis

A

glycogen synthesis

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6
Q

explain why it is beneficial for glucagon signals to stimulate both glycogenolysis and gluconeogenesis

A

both add sugar to the blood

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7
Q

name the enzyme that allows liver cells to convert glucose-6-phosphate —> glucose.
why is this enzyme needed for raising blood sugar?

A

glucose-6-phosphatase

necessary for liver glycogen to end up as blood sugar; once the phosphate is removed, the glucose is exportable

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8
Q

location of glucose-6-phosphatase

A

endoplasmic reticulum

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9
Q

name the enzyme:
glucose-1-phosphate <—–> glucose-6-phosphate

when would it go each direction?

A

phosphoglucomutase

in fasting state or during exercise (glycogenolysis), it goes the direction from G1P –> G6P

in glycogenesis, goes the direction where G6P —> G1P

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10
Q

donor of glucose rings to variety of building products, including addition of glucose rings to ends of branches of growing glycogen molecule in glycogenesis

A

UDP-glucose

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11
Q

name enzyme that phosphorylates glucose in muscle cells

A

hexokinase

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12
Q

name enzyme that phosphorylates glucose in liver cells

A

glucokinase

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13
Q

describe the rxn that forms UDP-glucose

A

glucose-1-phosphate reacts with UTP to produce pyrophosphate and UDP-glucose

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14
Q

name the enzyme that makes a pre-existing glycogen molecule bigger by one glucose ring

who’s the donor?

what’s the product?

A

glycogen synthase

UDP-glucose

UDP is a product

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15
Q

what type of linkages does glycogen synthase produce?

A

alpha-1,4 linkages

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16
Q

what enzyme helps to create branching in glycogen molecules by adding alpha-1,6 glycosidic linkages?

A

branching enzyme or 4:6 transferase

  • does NOT use UDP-glucose
  • does NOT make glycogen molecule any bigger, only restructures it
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17
Q

what enzyme breaks an alpha-1,4 linkage at the end of a branch to remove a glucose ring?

A

glycogen phosphorylase

18
Q

what type of rxn is the glycogen phosphorylase rxn?

A

phosphorylysis rxn

uses a Pi instead of water to break the alpha 1,4 linkage

19
Q

product in the glycogen phosphorylase rxn

A

glucose-1-phosphate

20
Q

what enzyme breaks down the alpha-1,6 linkages in glycogen?

what type of rxn is this

A

debrancher enzyme
hydrolysis rxn
- water goes in, breaking the alpha 1,6 linkage and releasing a small amount of glucose (bare naked glucose)

21
Q

what enzyme breaks an alpha 1,4 linkage and then will reattach the shortchain of glucoses, forming a 1,4 linkage elsewhere

A

4:4 transferase

22
Q

what enzyme catalyzes hydrolysis of 1,6 linkage in glycogen molecule, leavingone molecule of bare naked glucose?

A

alpha 1,6 glucosidase

23
Q

catalytic cofactor that resides in the active site of glycogen phosphorylase

A

pyridoxal phosphate (PLP), from vitamin B6 (pyrodoxin)

24
Q

predict effect of insulin signals on glycogenesis and glycogenolysis

A

speed up glycogenesis
slow down glycogenolysis

insulin stimulates glycogensis after a high carb meal

25
Q

predict the effect of glucagon signals on glycogenesis and glycogenolysis

A

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

26
Q

predict the effect of epinephrine on glycogenesis and glycogenolysis

A

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

27
Q

predict the effects of an increase in cytosolic level of cAMP

A

glucagon signals and epinephrine signals can increase levels of cAMP in cytosol, speeding up glycogenolysis

28
Q

predict the effects of an increase in cytosolic level of calcium ion

A

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

29
Q

effect of phosphorylating glycogen synthase

A

inactivates it

30
Q

effect of phosphorylating glycogen phosphorylase

A

activates it

31
Q

when would we want both glycogen synthase and glycogen phosphorylase to be phosphorylated?

what causes both enzymes to be phosphorylated?

A

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

32
Q

what enzymes can catalyze phosphorylation of glycogen synthase

A

a variety of enzymes (including phosphorylase kinase)

33
Q

what catalyzes phosphorylation of glycogen phosphorylase

A

phosphorylase kinase ONLY

34
Q

what enzyme catalyzes desphosphorylation of glycogen synthase and glycogen phosphorylase

what is the effect?

what hormone makes this happen?

A

protein phosphatase
- hydrolysis of phosphoester bond

glycogen synthase is active
glycogen phosphorylase is inactive

speeds up glycogenesis

insulin in the fasting state

35
Q

explain how glucagon receptors lead to increase glucose in the blood

A

glucagon receptors are heptahelical, heterotrimeric G-protein coupled.

  1. glucagon binds to heterotrimeric receptor
  2. receptor changes shape
  3. heterotrimeric g protein changes shape
  4. alpha subunit drops GDP and picks up GTP
  5. shape change activates adenylate cyclase
  6. cAMP concentration increases, becomes second messenger
  7. protein kinase A get activated which catalyzes phosphorylation of both phosphorylase kinase (activating it) & glycogen synthase (inactivating)
  8. catalyzes the breakdown glycogen (glycogenolysis)
  9. formation of glucose-1-phosphate that can become glucose-6-phosphate by phosphoglucomutase
  10. glucose-6-phosphatase rxn turns glucose-6-phosphate to glucose that can be exported to the blood
36
Q

insulin signals lead to activation of a protein phosphatase called ______________

what happens next?

A

protein phosphatase 1 (PP1)

causes glycogen synthase to be dephosphorylated, making it active

UDP-glucose can then be used to make glycogen

37
Q

enzymes that can be desphosphorylated by PP1

A 
glycogen synthase
glycogen phosphorylase (inhibits)
phosphorylase kinase (inhibits)
38
Q

what enzyme catalyzes the hydrolysis of cAMP —> AMP

what happens after this rxn occurs?

what hormone causes this?

A

cAMP phosphodiesterase

the effects:
protein kinase A won’t be activated anymore

insulin signals

39
Q

effects of glucagon signals on cAMP

effect of insulin signals on cAMP

A

glucagon raises cAMP levels

insulin lowers cAMP levels

40
Q

receptors for epinephrine are ___________ receptors

A

adrenergic

41
Q

signal transduction mechanism for when epinephrine binds to a beta-adrenergic receptor of a liver cell

explain.

A

adenylate cyclase system

  1. epinephrine binds to heptahelical receptor of liver cell
  2. receptor changes shape.
  3. heterotrimeric G protein senses shape change
  4. alpha subunit drop GDP and picks up GTP
  5. adenylate cyclase activated
  6. cAMP concentration increases, becomes second messenger
  7. 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

42
Q

signal transduction when epinephrine binds to an alpha-1 adrenergic receptor of a liver cell

explain

A

phospholipase c.

  1. epinephrine binds to alpha-1 heptahelical receptor of a liver cell
  2. receptor changes shape.
  3. heterotrimeric G protein senses shape change
  4. alpha-subunit drops GDP and picks up a GTP
  5. activates phospholipase C (membrane-associated enzyme)
  6. breaks the membrane phospholipid molecule into two pieces that serve as second messengers (DAG & inositol triphosphate)
  7. IP3 receptors on the endoplasmic reticulum opens doors for calcium ion
  8. Ca2+ passively flows out of ER into cytosol
    DAG and Ca2+ released from the ER activate several protein kinases (including phosphorylase kinase)
  9. Ca2+ binds to calmodulin (direct allosteric activation of phosphorylase kinase)
  10. phosphorylase kinase catalyzes phosphorylation of glycogen phosphorylase & glycogen synthase
  11. glycogenolysis is sped up by epinephrine

Endocrine Biochem (7 decks)

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