Glucogen Synthesis and Regulation Flashcards
Diffrence in function and structure of glucose vs glycogen
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
What is liver glycogen responsible for?
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
What is muscle glycogen responsible for?
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
How is glycogen used as fuel in muscle for exercise?
Glycogen in muscle is broken down and degraded into glucose 6-p then it enters glycolyissis to provide energy for contraction
Describe glycogen’s structure?
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
Features of biosynthetic pathways
* 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
What are the first stages of glycogen synthesis from glucose?
STEP 1
Glycose to glycogen
- ATP used
step 1
Glucose ——-> Glucose 6-phosphate <——> Glucose 1-phosphate
Enzymes
- hexokinase
-glucokinase
- phosphoglucomutase
Step 2 of glycogen synthesis from glucose?
slide 11
FORMATION OF UDP GLUCOSE
Transferase enzyme
GLUCOSE-1-P + UTP ———————————> PPi (phosphate) + UDP Glucose
- Put in energy (Anabolic pathway)
Step 2 of glycogen synthesis from glucose?
slide 12
ADDITION OF GLUCOSE UNIT TO PROTEIN PRIMER
UDP-glucose + Protein Primer (GLYCOGENIN)
————–> UDP
- Use glycogen synthase
Step 3 of glycogen synthesis from glucose?
slide 13
UDP-glucose used and UDP removed
Glucose released and forms a 1-4 glycosidic linkages between glucose
Step 4 of glycogen synthesis from glucose?
slide 14
BRANCH POINTS are introduced into the structure of glycogen
- branches off from glucose
- forms a 1-6 bond
How the branched structure of glycogen formed?
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
How is Glycogen synthase regulated?
**By Phosphorlylation
How is glycogen synthase activated?
Activated - By dephosphorlyation
Protein phosphatase used
Phosphate removed
How is glycogen synthase inactivated?
Inactivated byphosphorlation
* Protein Kinase Used
* ATP used
* Pi added
Phosphorlyase Vs Phosphatase
Phosphorlyase - Hydrolyses and uses organic phosphorylase
Phosphatase - removes phosphate
How are glycogen broken down?
Using glycogen phosphorylase enzyme and pi
glycogen phosphorylase attacks the end of chains which are the sites of phosphorylase action
How are the remaning glycogen broken down?
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
What does the breakdown of glycogen produce?
glycogen breakdown by phosphorylase results in the production of glucose-1-phosphate
How is glucose produced from this?
glucose-1-phosphate —–>glucose-6-P
mutase enzyme used
glucose-6-P ——>Glucose
glucose -6-phosphatase
Glucose then realsead in blood stream
Why does breakdown into glycose differ in muscles and liver?
glucose -6-phosphatase enzyme is in liver only not the muscles
so muscle glycose is not produce instead glucose-6-P goes through glycolysis
How is GLYCOGEN PHOSPHORYLASE regulated?
Activated? Inactivated?
By Phospholation
Activation - Adding phosphate through protein kinase
Inactivated - removing phosphate through adding protien phosphatase
Why are the pathways opposite?
Synthesis and degradation does not occur at the same time
If one is occuring, the other is inhibited
In order to stop futile cycles
What are the protein kinase enzymes dependent on?
Describe structure and formation of this molecules?
cAMP
How does the cordinated regulation of synthesis/breakdown of glycogen occur?
Protein kinase - uses ATP - Activates phospholyste and inactivates synthase
Protein phosphatase - activates synthates + inactivates phosphorlation for breakdown
How is cordinated regulation of synthesis/breakdown of glycogen triggered?
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
Overview of glycogen breakdown?
How is adenylate cyclase used in this reaction?
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
What’s an additional glycogen control in liver?
The liver responds to insulin/glucagon
When glucose is high it binds to the glycogen phosphorylase and inactivates it.
What’s 2 additional glycogen control in muscles?
- 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 - 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
3 examples of glycogen storgage diseases?
