glycogen metabolsim

Question 1

what is glycogen in the liver used for vs in the muscle?

Answer 1

in liver- used to raise blood glucose, in muscle used locally for mm work

Question 2

liver glycogen is the main glucose source during-

Answer 2

overnight fast

Question 3

bonds in glycogen (2)

Answer 3

a1,4- linear

a1,6- branches

Question 4

MOA of glycogen phosphorylase

Answer 4

uses Pi to cleave a1,4 bonds = glucose-1-p

B6 is a cofactor

Question 5

MOA of debranching enzyme

Answer 5

at 4 residues away from branch site glycogen phosphorylase will stop and deb ranching enzyme will take over- it was transfer 3 residues to the linear part (4:4 transferase) and it will use a1,6 glucosidase activity to release 1 free glucose

Question 6

why is it important for glycogen to be branched? (3)

Answer 6

• less osmotically active
• rapid glycogenolysis
• long unbranched polymers are cytotoxic

Question 7

andersen disease

Answer 7

glycogen storage disease, lack branching enzyme, end up with long glycogen chains, leads to cirrhosis

Question 8

2 steps of glycogenolysis in mm

Answer 8

glycogen –> glucose-1-P by glycogen phosphorylase
glucose-1-P –> glucose-6-P by phosphoglucomutase
glucose-6-P feeds into glycolysis

Question 9

3 steps of glycogenolysis in liver

Answer 9

glycogen –> glucose-1-P by glycogen phosphorylase
glucose-1-P –> glucose-6-P by phosphoglucomutase
glucose-6-P –> glucose by glucose-6-phosphatase
glucose enters blood via GLUT2

Question 10

what happens when epinephrine binds b-adrenergic receptor?

Answer 10

inc cAMP
activates PKA
activates phosphorylase kinase
activates glycogen phosphorylase=
inc glycogenolysis=
increased blood glucose

Question 11

what hormones regulate glycogenolysis in liver?

Answer 11

epinephrine

glucagon

Question 12

what are the covalent modifications that regulate glycogenolysis in liver?

Answer 12

phosphorylase kinase will add P to glycogen phosphorylase to activate it

Question 13

what is an allosteric inhibitor of glycogen phosphorylase in liver?

Answer 13

high glucose levels = will block glycogenolysis

Question 14

what are the 3 stimulators of glycogen mobilization in muscle?

Answer 14

epinephrine
mm contraction
nerve impulses via calcium

Question 15

why does glucagon not act on mm?

Answer 15

mm lacks glucagon receptors

Question 16

what is required for “full” activation of glycogen phosphorylase?

Answer 16

Ca-calmodulin

phosphorylase kinase-P

Question 17

what is the unique way that mm regulates glycogenolysis?

Answer 17

muscle contraction leads to increased ADP
adenylate kinase converts ADP to ATP +AMP
AMP will allosterically promote activity of glycogen phosphorylase b (a weaker form of glycogen phosphorylase)

Question 18

how is an “active glucose unit” formed?

Answer 18

glucose enters cell and is phosphorylated by hexokinase or glucokinase to form glucose-6-P, phosphoglucomutase converts that to glucose-1-P, UDP-pyrophosphorylase converts that to UDP-glucse (active form) and PPi

Question 19

where is UDP-glucose added to the growing glycogen chain?

Answer 19

non-reducing end

Question 20

2 enzymes used in glycogen synthesis

Answer 20

glycogen synthase- a1,4- adds 1 glucose in linear fashion
branching enzyme (4:6 transferase)- adds 6-7 glucoses to branch

Question 21

what is glycogenin?

Answer 21

protein that self-glycosylates to form initial glycogen primer, capable of doing this because it has “intrinsic glucosyltransferase activity” that adds UDP-glucose to OH of tyrosine residue, can add total of 8 glucoses

Question 22

what is the catalyst needed for glycogenin?

Answer 22

Mn2+

Question 23

what is the inactive form of glycogen synthase?

Answer 23

phosphorylated form

Question 24

what is the main phosphorylator of glycogen synthase?

Answer 24

glycogen synthase kinase 3 (GSK3)

Question 25

what is the MOA of GSK3?

Answer 25

phosphorylates 3 serine residues on glycogen synthase to make it inactive

Question 26

what is responsible for activating GSK3?

Answer 26

casein kinase (CKII)

Question 27

what is glycogen synthase D?

Answer 27

form of glycogen synthase that is dependent on glucose- this form is has limited activity, even in the phosphorylated state, when glucose-6-P levels are high

Question 28

what is the role of insulin in glycogen formation?

Answer 28

insulin promotes glycogen formation

Question 29

how does insulin promote glycogen formation? (2)

Answer 29

• blocks GSK3 activity

- activates protein phosphatase 1 (removes P from glycogen synthase to activate it)

Question 30

what are glycogen-targeting proteins (Gm)?

Answer 30

large protein complexes that bind: glycogen, glycogen synthase, glycogen phsophorylase and phosphorylase kinase

Question 31

what are the 2 phosphorylation sites on Gm?

Answer 31

site 1- P stim by insulin = PP1 = glycogen synthesis

site 2- P stim by epinephrine/PKA = PP1 is released from the complex and cannot act on substrate

Question 32

what is inhibitor 1?

Answer 32

inhibits PP1, activated by PKA