SYLLABUS 6: Glycogen Metabolism Flashcards Preview

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Flashcards in SYLLABUS 6: Glycogen Metabolism Deck (37):
1

what is glycogen

storage form of glucose 

made up of many glucose units linked together by C1 of 1 glucose - C4 of adjacent glucose

C1-C6 links btwn glucoses make branches 

 

2

what does branching do for glycogen

increases soubility 

allows several avialable sites to be degraded simultaneously 

3

under what conditions is glycogen made / broken down?

made: high energy, carbs, glucose conditions

broken down: low-energy, carbs, glucose conditions; vigorous exercise/stress; diabetes

4

where is glycogen stored

the cytosol of cells

most in liver, muscle 

 

5

function of glycogen in liver

produce glucose to release to other tissues that need energy 

6

function of  glycogen in muscles

provide mucle with glucose in times of need - eg exercise, fight, flight

7

what does glycogen breakdown

1) phosphorylase 

2) debranching enzyme

8

what is the reaction of phosphorylase on glycogen

(glycogen)n + P-> (glycogen)n-1 + G1P

this is IRREVERSIBLE

9

describe how glycogen break down occurs 

1) phosphorylates breaksdown glycogen to a smaller glycogen by 1 unit of glucose, + G1P 

removal of glucose unit occurs repeatedly until 4 residues from a branch point 

2) debranching enzyme moves 3 of the 4 residues to another chain 

3) the 4th residue, in the 1-6 glycosidic bond w/ the other chain, is hydrolyzed by the glucosidase activity of the debranching enzyme 

this produces glucose + a straight polymer 

4) phosphorylase continues to degrade teh straight polymer to G1P til the next branch point 

 

10

what happens to the G1P produced from glycogen breakdown?

1) G1P is muated to G6P by phophoglucomutase 

2) G6P enters glycolysis in the muscle or liver 

3) G6P is hydrolyzed to glucose 

4) glucose exits into the blood to be transported to other tissues 

 

11

when is glycogen phoshphorylase active vs inactive

active: phosphorylated state 

inactive: dephosphorylated state 

12

what is glucagon in the liver, epi in the liver in muscle's, effect on glycogen breakdown

glucagon and epinephrine activate G proteins 

G proteins activate adenylyl cyclase to make cAMP 

cAMP activates PKA 

activated cAMP-PKA promotes phosphorylation of phosphorylase kinase, makes it ACTIVE 

so GLUCAGON AND EPI cause the ACTIVE, PHOSPHORYLATED state of PHOSPHORYLASE, which means GLYCOGEN BREAKDOWN occurs

13

what is insulin's impact on phosphorylase/glycogen breakdown?

insulin stimulates protein phosphatases 

this promotes the dephosphorylated state of phosphorylase 

this makes phosphorylase INACTIVE 

so NO GLYCOGEN BREAKDOWN occurs

14

what kind of action does phosphorylase do

phosphoralysis

15

what kind of action does the debranching enzyme do

hydrolysis 

16

when is glycogen synthesized?

high energy conditions; when have lots of glucose 

 

17

how does glycogen synthesis occur?

1) G6P -> G1P by phosphoglucomutase 

2) G1P -> UDP-glucose + PPi, by UTP 

this UDP-glucose adds glucose residues on to an already existing glycogen, extends it 

the PPi is cleaved to 2Pi 

UDP-glucose adds new glucose units to the core primer glucose in 1-4 glycosidic bonds 

 

18

how many high energy bonds does glycogen synthesis require

requires 3 high energy bonds to add 1 glucose to a glycogen polymer:

1 from ATP to go from glucose to G6P,

2 from formation of UDP-glucose w/ release of PPi, which is hydrolyzed to Pi 

19

what is glycogenin 

small protein core of the glycogen polymer wehre a tyrosine-OH is linked to 1 or more glucose residues 

it's here that UDP-glucose adds new glucose units, in 1-4 glycosidic bonds

20

what catalyzes the addition of a glucose residue to a glycogen polymer? what kind of rxn is this?

glycogen synthase 

IRREVERSIBLE 

 

21

how is a branch of glucose links added to glycogen

once glycogen synthase irreversibly builds up a number of glucose links, 

branching enzyme transfers 6-7 glucose residues from the end of its chain -> C6-OH group of a glucose residue in another chain 

this forms the 1-6 branching points 

22

what is high level of G6P effect on glycogen synthase?

activates it 

23

when is glycogen synthase active?

ACTIVE in the DEPHOSPHORYLATED state

INACTIVE in the PHOSPHORYLATED state 

24

insulin's effect on the glycogen synthesis enzymes?

HIGH levels of insulin stimulates PROTEIN PHOSPHATASE 1

this DEPHOSPHORYLATES phosphorylase and glycogen synthase

ACTIVATES glycogen synthase -> INCREASES glucose utilization 

INACTIVATES phosphorylase -> DECREASES glycogen breakdown

25

what are the effects of glucagon/epi on glycogen synthesis?

INCREASE in EPI in MUSCLE or EPI/GLUCAGON in LIVER: 

promotes PHOSPHORYLATED state

this STIMULATES GLYCOGEN BREAKDOWN by phoshporylating phosphorylase 

this iNHIBITS GLYCOGEN SYNTHESIS by promoting phosphorylation of glycogen synthase

26

what phosphorylates glycogen synthase?

cAMP-PKA

this inactivates it

27

what occurs to phosphorylate and activate phosphorylase?

1) cAMP-PKA phosphorylates phosphorylase kinase 

this activates phosphorylase kinase

2) activated phosphorylase kinase phosphorylates phosphrylase 

this activates phosphorylase

28

what is the impact of an INCREASE IN EPI in Muscle

INCREASES glycogen breakdown 

this PRODUCES G6P

G6P enters GLYCOLYSIS and ATP production for exercise, fight, flight, or stress

29

what is impact of INCREASED EPI/GLUCAGON on LIVER

Epi and Glucagon transcriptionally activate 6-phosphatase, an enzyme present in liver and not in muscle 

6-phosphatase hydrolyzes G6P to glucose + Pi

this glucose then leaves the liver -> other tissue 

 

30

why doesn't increased epi/glucagon in liver cause -> glycolysis?

INCREASED epi/glucagon = DECREASED F2,6bisP

DECREASED F2,6 bis P = INCREASED the G6Pase 

this blocks glycolysis and keeps G6P from hydrolyzing to glucose 

31

why can G6P in the muscle enter glycolysis in the presence of increased epi? why doesn't it get broken down to glucose, like in the liver?

the isoforms of F2,6 bis P kinase and phosphatase in muscle are different from those in the liver; they show opposite properties: 

phosphorylation INCREASES the kinase activity, and DECREASES the phosphatase activity, in muscle, thus INCREASING F2,6 bis P levels and stimulating PFK activity and glycolysis in muscle 

 

32

what's the difference btwn the F2,6 bis P in liver vs muscle

MUSCLE F2,6 bis P is a POSITIVE effector, stimulator, of PFK; so high EPI levels -> glycolysis

LIVER F2,6 bis P is an INHIBITOR of PFK; so high EPI levels -> glucose -> other tissues

33

what causes neuronal signal for glycogen breakdown in muscle?

INCREASE in EPI -> INCREASE in Calcium 

Calcium binds Calmodulin, a subunit of Phosphorylase kinase, and activates it - even when it's in its low-active dephosphorylated state 

this PROMOTES GLYCOGEN breakdown 

this provides neuronal signal for regulation of glycogen breakdown

34

how does phosphorylase act as a "glucose sensor" in the liver?

in absence of glucose, phosphorylase binds protein phosphatase-1

this prevents phosphatase from dephosphorylating phosphorylase (= ACTIVE) and glycogen synthase (= INACTIVE)

so no glycogen synthesis occurs in the absence of glucose

 

in the presence of glucose, 

glucose binds phosphorylase

this causes a conformational change, releases phosphatase-1 from phosphorylase 

now phosphatase-1 is free; dephosphorylates phosphorylase (= INACTIVE) and glycogen synthase (= ACTIVE)

this allows glycogen to be synthesized in high glucose conditions

35

what causes glycogen storage diseases

glycogen breakdown is blocked 

this interferes w/ liver's ability to provide glucose & muscle's ability to carry out muscular function under stress conditions

36

what organs can glycogen storage diseases impact

liver primarily 

also organs with lysosomes 

skeletal muscle 

heart 

RBC

37

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