SYLLABUS 6: Glycogen Metabolism

Question 1

what is glycogen

Answer 1

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

Question 2

what does branching do for glycogen

Answer 2

increases soubility

allows several avialable sites to be degraded simultaneously

Question 3

under what conditions is glycogen made / broken down?

Answer 3

made: high energy, carbs, glucose conditions

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

Question 4

where is glycogen stored

Answer 4

the cytosol of cells

most in liver, muscle

Question 5

function of glycogen in liver

Answer 5

produce glucose to release to other tissues that need energy

Question 6

function of glycogen in muscles

Answer 6

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

Question 7

what does glycogen breakdown

Answer 7

1) phosphorylase
2) debranching enzyme

Question 8

what is the reaction of phosphorylase on glycogen

Answer 8

(glycogen)_n + P_i-> (glycogen)_n-1 + G1P

this is IRREVERSIBLE

Question 9

describe how glycogen break down occurs

Answer 9

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

Question 10

what happens to the G1P produced from glycogen breakdown?

Answer 10

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

Question 11

when is glycogen phoshphorylase active vs inactive

Answer 11

active: phosphorylated state
inactive: dephosphorylated state

Question 12

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

Answer 12

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

Question 13

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

Answer 13

insulin stimulates protein phosphatases

this promotes the dephosphorylated state of phosphorylase

this makes phosphorylase INACTIVE

so NO GLYCOGEN BREAKDOWN occurs

Question 14

what kind of action does phosphorylase do

Answer 14

phosphoralysis

Question 15

what kind of action does the debranching enzyme do

Answer 15

hydrolysis

Question 16

when is glycogen synthesized?

Answer 16

high energy conditions; when have lots of glucose

Question 17

how does glycogen synthesis occur?

Answer 17

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

Question 18

how many high energy bonds does glycogen synthesis require

Answer 18

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

Question 19

what is glycogenin

Answer 19

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

Question 20

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

Answer 20

glycogen synthase

IRREVERSIBLE

Question 21

how is a branch of glucose links added to glycogen

Answer 21

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

Question 22

what is high level of G6P effect on glycogen synthase?

Answer 22

activates it

Question 23

when is glycogen synthase active?

Answer 23

ACTIVE in the DEPHOSPHORYLATED state

INACTIVE in the PHOSPHORYLATED state

Question 24

insulin’s effect on the glycogen synthesis enzymes?

Answer 24

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

Question 25

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

Answer 25

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

Question 26

what phosphorylates glycogen synthase?

Answer 26

cAMP-PKA

this inactivates it

Question 27

what occurs to phosphorylate and activate phosphorylase?

Answer 27

1) cAMP-PKA phosphorylates **phosphorylase kinase **

this activates phosphorylase kinase

2) activated phosphorylase kinase **phosphorylates phosphrylase **

this activates phosphorylase

Question 28

what is the impact of an INCREASE IN EPI in Muscle

Answer 28

INCREASES glycogen breakdown

this PRODUCES G6P

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

Question 29

what is impact of INCREASED EPI/GLUCAGON on LIVER

Answer 29

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

Question 30

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

Answer 30

INCREASED epi/glucagon = DECREASED F2,6bisP

DECREASED F2,6 bis P = INCREASED the G6Pase

this blocks glycolysis and keeps G6P from hydrolyzing to glucose

Question 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?

Answer 31

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

Question 32

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

Answer 32

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

Question 33

what causes neuronal signal for glycogen breakdown in muscle?

Answer 33

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

Question 34

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

Answer 34

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

Question 35

what causes glycogen storage diseases

Answer 35

glycogen breakdown is blocked

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

Question 36

what organs can glycogen storage diseases impact

Answer 36

liver primarily

also organs with lysosomes

skeletal muscle

heart

RBC