Glucogen Synthesis and Regulation

Question 1

Diffrence in function and structure of glucose vs glycogen

Answer 1

Glycogen is polymer of glucose
monosaccharide vs polysaccharide
Gluocse - 10g
glucose can instead be stored as glycogen - 400g in tissue stores
as glucose is osmatically active but glucagon has low osmarlity

Question 2

What is liver glycogen responsible for?

Answer 2

The liver is sensitive to blood glucose concentration
Glucogen conc is larger per gram in liver then muscle but there are more muscles then liver

liver maintains constant levels of glucose in the blood using insulin ang glycagon

Question 3

What is muscle glycogen responsible for?

Answer 3

rapid source of glucose for muscle contraction
The muscle is sensitive to energy needs of the tissue
It is sensitive to adrenaline, calcium, AMP, ATP

Question 4

How is glycogen used as fuel in muscle for exercise?

Answer 4

Glycogen in muscle is broken down and degraded into glucose 6-p then it enters glycolyissis to provide energy for contraction

Question 5

Describe glycogen’s structure?

Answer 5

Glycogen has a branched structure
a 1-4 glycoside linkages
a 1-6 glycoside linkages

End - terminal end
When glycogen starts - resducing end of polymer

Question 6

Features of biosynthetic pathways

Answer 6

* ATP or UTP or GTP (input of energy needed) are needed as cofactors (to ‘drive the reactions forward’)
* one or more enzyme reactions will be irreversible, and alternative enzymes are used for the ‘opposite direction’
* enzyme reactions at the beginning or end of the pathway are tightly regulated

Question 7

What are the first stages of glycogen synthesis from glucose?
STEP 1

Answer 7

Glycose to glycogen
- ATP used
step 1
Glucose ——-> Glucose 6-phosphate <——> Glucose 1-phosphate

Enzymes
- hexokinase
-glucokinase
- phosphoglucomutase

Question 8

Step 2 of glycogen synthesis from glucose?

slide 11

Answer 8

FORMATION OF UDP GLUCOSE

Transferase enzyme

GLUCOSE-1-P + UTP ———————————> PPi (phosphate) + UDP Glucose

• Put in energy (Anabolic pathway)

Question 9

Step 2 of glycogen synthesis from glucose?

slide 12

Answer 9

ADDITION OF GLUCOSE UNIT TO PROTEIN PRIMER

UDP-glucose + Protein Primer (GLYCOGENIN)
————–> UDP

• Use glycogen synthase

Question 10

Step 3 of glycogen synthesis from glucose?
slide 13

Answer 10

UDP-glucose used and UDP removed
Glucose released and forms a 1-4 glycosidic linkages between glucose

Question 11

Step 4 of glycogen synthesis from glucose?
slide 14

Answer 11

BRANCH POINTS are introduced into the structure of glycogen

• branches off from glucose
• forms a 1-6 bond

Question 12

How the branched structure of glycogen formed?

Answer 12

Glycogen synthase and branching enzyme produce the branched structure of glycogen

branching enzyme introduces site for new chains

Glycogen synthase enzyme extends the straight chains

Site of action of branching enzyme - about 5 units

Question 13

How is Glycogen synthase regulated?

Answer 13

**By Phosphorlylation

Question 14

How is glycogen synthase activated?

Answer 14

Activated - By dephosphorlyation
Protein phosphatase used
Phosphate removed

Question 15

How is glycogen synthase inactivated?

Answer 15

Inactivated byphosphorlation
* Protein Kinase Used
* ATP used
* Pi added

Question 16

Phosphorlyase Vs Phosphatase

Answer 16

Phosphorlyase - Hydrolyses and uses organic phosphorylase
Phosphatase - removes phosphate

Question 17

How are glycogen broken down?

Answer 17

Using glycogen phosphorylase enzyme and pi
glycogen phosphorylase attacks the end of chains which are the sites of phosphorylase action

Question 18

How are the remaning glycogen broken down?

Answer 18

removal of glucose units from branched regions requires debranching enzyme
* 1,6 glycoside link hydrolysed by debranching enzyme
* straight chain regions degraded further by glycogen phosphorylase
acting on 1,4 links

Question 19

What does the breakdown of glycogen produce?

Answer 19

glycogen breakdown by phosphorylase results in the production of glucose-1-phosphate

Question 20

How is glucose produced from this?

Answer 20

glucose-1-phosphate —–>glucose-6-P
mutase enzyme used
glucose-6-P ——>Glucose
glucose -6-phosphatase

Glucose then realsead in blood stream

Question 21

Why does breakdown into glycose differ in muscles and liver?

Answer 21

glucose -6-phosphatase enzyme is in liver only not the muscles
so muscle glycose is not produce instead glucose-6-P goes through glycolysis

Question 22

How is GLYCOGEN PHOSPHORYLASE regulated?
Activated? Inactivated?

Answer 22

By Phospholation
Activation - Adding phosphate through protein kinase
Inactivated - removing phosphate through adding protien phosphatase

Question 23

Why are the pathways opposite?

Answer 23

Synthesis and degradation does not occur at the same time
If one is occuring, the other is inhibited
In order to stop futile cycles

Question 24

What are the protein kinase enzymes dependent on?
Describe structure and formation of this molecules?

Answer 24

cAMP

Question 25

How does the cordinated regulation of synthesis/breakdown of glycogen occur?

Answer 25

Protein kinase - uses ATP - Activates phospholyste and inactivates synthase
Protein phosphatase - activates synthates + inactivates phosphorlation for breakdown

Question 26

How is cordinated regulation of synthesis/breakdown of glycogen triggered?

Answer 26

Insulin activates protein phosphatase enzyme
higher blood glucose = synthesis of glycogen needed to lower glucose
Adrenaline (muscle)/ glucagon (liver) activates protien kinase
Lower blood glucose = breakdown of glycogen to rise glucose

Question 27

Overview of glycogen breakdown?

Answer 27

Question 28

How is adenylate cyclase used in this reaction?

Answer 28

Adrenaline/ glycogon activates adenylate cyclase in membrane which is activated and with ATP produces cAMP which activates protein kinase

Protein kinase made up of 4 subunits - 2 regulatory and 2 catalytic
Splits protein kinase to activate it
This catalytic compent of protein kinase will then activate glycogen phosphorylase kinase for degradation

Question 29

What’s an additional glycogen control in liver?

Answer 29

The liver responds to insulin/glucagon
When glucose is high it binds to the glycogen phosphorylase and inactivates it.

Question 30

What’s 2 additional glycogen control in muscles?

Answer 30

1. During muscular contraction, Calcium ions are released into the sarcoplasmic reticulum.
   Calcium binds the calmodulin domain of glycogen phosphorylase kinase and activates the enzyme
   This in turn activates the phosphorylase and glycogen is degraded providing energy for contracting muscle
2. In prolonged exercise, ATP concentrations are reduced and AMP concentrations begin to rise.
   AMP is an allosteric activator of glycogen phosphorylase.
   Glycogen degradation continues without the need for hormonal interaction
   ATP is an allosteric inhibitor, so that when energy levels are high, glycogen breakdown stops

Question 31

3 examples of glycogen storgage diseases?

Answer 31