Glycogen Metabolism

Question 1

glycogen is found in what tissues?

Answer 1

liver

skeletal muscle

heart

kidney

Question 2

what are the major differences between liver and muscle glycogen?

Answer 2

• liver glycogen
  
  • responsive to glucagon + epinpherine
  • gives glucose from glycogenolysis to other tissues
• muscle glycogen
  
  • responsive to epinephrine only (muscle does not have glucagon receptors)
  • uses glucose from glycogenolysis for itself

Question 3

describe the structure of glucose

Answer 3

highly branched structure made of a1-4 inkages w/ a1-6 branch points

Question 4

what are general steps to glycogen synthesis?

Answer 4

1. glucose activation: Glu-6-P (from glycolysis) –> UDP-glucose
2. lengthening of glycogen polymer
   
   • normal linkages: a1-4
   • branch points: a1-6

Question 5

what is the starting material for glycogen synthesis?

what initial steps must it undergo?

Answer 5

• G-6-P = start point (glycolytic intermediate)
  
  • undergoes activation:
    
    • _​_G-6-P –> G-1-P by phosphoglucomutase
    • G-1-P + UTP –> UDP-glucose by UDP-glucose pyrophosphorylase
      
      • ​UDP-glucose can be added to glycogen

Question 6

discuss the steps for lengthening the glycogen polymer

Answer 6

• glycogen prepped with glycogenin (primer)
• UDP-glucose residues added one at a time to “non-reducing” end (4’ C) of glycogen by glycogen synthase
  
  • ​forms a-1,4 linkage

Question 7

discuss the steps for synthesizing glycogen branch points

Answer 7

1. after a minimum of 11 glycosyl residues (placed a1-4 by glycogen synthase) have been added, the terminal 6-7 residues are removed as a block
2. banching enzyme: adds one end of this block to glycogen in alpha 1-6 inkage

Question 8

outline the steps of glycogenolysis

Answer 8

• non-branch points:
  
  • glycogen phosphorylase removes units from non-reducing end –> G-1-P
• branch points:
  
  • glycogen phosphorylase removes units until branch is 4 units long
  • then, debranching enzyme:
    
    1. glucan transferase activity: moves distal branch 3 units (triose) to glycogen terminus
    • alpha1-6 glucosidase activity: hydrolyzes branch point –> glucose

Question 9

glycogen phosphorylase

• acts on what glycogen bonds?
• yield what products
• requires?

Answer 9

• alpha-1,4 bonds
• yields: glucose-1-phosphate
• requires: pyroxidal phosphate (vitamin B derivative)

Question 10

debranching enzyme

• acts on what glycogen bonds?
• yields what products?
• requires?

Answer 10

• acts on: a-1,4 and a-1,6 bonds of 4 unit branch
• yields: glucose
• requires:
  
  • glucan transferase activity: transfers branch triose to glycogen end
  • a-1,6 glucosidase acitivity: removes branch residue

Question 11

what major hormones influence glycogen metabolism and how do they do this?

Answer 11

• glycogenesis
  
  • stimulated by: insulin
  • inhibited by: glucagon
• glycogenolysis
  
  • stimulated by:
    
    • glucagon - liver
    • epinephrine -liver and muscle
  • inhibitede by: insulin

Question 12

what hormones promote glycogenolysis?

what cascade do they induce & how?

Answer 12

glucagon and epinephrin:

bind cAMP-linked GCPR (Gs), inducing cAMP dependendent phosphorylation cascade:

• ​cAMP phosposphorylates:
  
  • phosphorylase kinase b –> phosphorylase kinase a ​(active form), which phosphorylates
    
    • glycogen phosphorylase b –> glycogen phosphorylase a (active form)
    • inhibitor 1b --> inhibitor 1a (active form)
      
      • inhibits phosphotases to prevent deposphorylation & inactviation of
        
        1. phosphorylase kinase a , and
        2. glycogen phosphorylase a

Question 13

in what state is gycogen phosphorylase active?

what promotes this tate?

Answer 13

• phosphorylase a.
  
  • promoted by
    
    1. glucose (substrate)
    2. ATP (- glycolysis)
    3. phosphorylase kinase a, from
       
       1. cAMP - glucagon/epinephrin binding
       2. Ca++

Question 14

in what state is glycogen synthase active? inactive?

Answer 14

• active: glycogen synthase a - dephosphorylated
• inactive: glycogen synthaes b - phosphorylated

Question 15

how does a insulin dominant state effect glycogen synthase?

Answer 15

• insulin triggers “depophosphoryalation” cascade, promoting glycogenesis
  
  • dephosphorylates inhibitor 1a-P (active) to its inhibitor 1b (inactive)
    
    • this inhibits dephosphorylation & inhibition of phosphorpotein phosphotase
      
      • ​active phosphoprotein phosphotase dephosphorylates and active glycogen synthase-b-P –> glycogen synthase a –> glycogensynthesis proceeds

Question 16

how does a glucagon dominant state effect glycogen synthase?

Answer 16

• glucagon triggers a “phosphorylation” state, inhibiting glycogenesis
  
  • a host of protein kinases from secondary messenger systems - PKA, PKC, calmondulin dependent kinase - phosphorylate & inactivate
    
    • glycogen synthase a –> glycogen synthase b-P (inactive form)
  • cAMP (PKA) phosphorylates & activates
    
    • inhibitor B –> inhibitor 1a-P, which phosphorylates & inactivate
      
      • protein phosphotase
        
        • whicg preventing from dephosphorylating glycogen synthase b-P

Question 17

epinephrine has what net effects on glucose metabolism?

Answer 17

• in the liver
  
  • stimulates gluconeogenesis
  • stimulate glycogenolysis
  • inhibits glycolysis
• in the muscle
  
  • stimuates glycogenolysis
  • stimulates glycolysis

Question 18

what are glycogen storage disease?

Answer 18

a group of inherited disorders characterized by

• deposition of abnormal quantity/type of glycogen
• failure to mobilize glycogen

Question 19

what enzyme is effects by GSD0a storage diseaes?

Answer 19

glycogen synthase

Question 20

what enzyme is effected in Cori (Forbes) storage disease?

Answer 20

debranching enzyme

(in liver and muscle)

Question 21

what enzyme is affected by Andersen (glyogen storage) disease?

Answer 21

branching enzyme

Question 22

what enzyme is affected by McArdle (glyogen storage) disease?

Answer 22

glycogen phosphorylase in muscle

Question 23

what enzyme is affected in Hers (gycogen storage) disease?

Answer 23

glycogen phosphorylase - in the liver

Question 24

what enzyme is effected by GSD9 (glycogen phosphorylase) enzyme

Answer 24

glycogen phosphorylase kinase

Question 25

Answer 25