Glycogen synthesis and mobilisation Flashcards
glycogen is …
a store of glucose
what is the two roles of glycogen
- In the liver – it is used to maintain glucose levels in the blood
- In the muscle – it is used to maintain glucose supply to muscle during bursts of activity and contractions, this provides ATP aerobically or anaerobically
where is the majority of glycogen in the body
the muscles
what are the characteristics of glycogen as a store of glucose
- Easily to store and access therefore it is quick and easy to make and breakdown
- Stores glycogen
- Less osmotically active therefore doesn’t effect the water balance of the cells, it causes less water to come into the cell and this prevents bursting
- Acts as a glucose buffer
- The only tissue that can export glucose back to the blood is the liver
- Muscle glycogen can only go into glycolysis therefore it can only be used in the cell where that glycogen is
glycogen is a …
polymer of glucose
how does the chain of glycogen start
- Needs a primer (this is where the glycogen chain starts) – protein glycogenin
explain how the main chain of glycogen is formed simply
- Needs a primer (this is where the glycogen chain starts) – protein glycogenin
- Extended with 1-4 links to form a chain adding at the end
- We extend the chain at the carbon 4 end
- Glycogen synthase adds glucose to the chain making 1-4 links
is glycogen branched or not
- yes it is branched it has 1-6 branching
when does branching occur
every 12-14 residues
what does branching do to glycogen
- There are branches so there are more ends this means that it is easier to remove things and add things and helps with its solubility inside the cell as well, makes it easier to break of a branch of glycogen and convert it to glucose
how does branching occur
- Every 12-14 residues along the main chain a glucose is linked from carbon 6
- To become branched branching enzymes adds branches linked to carbon 6 – 1-6 linkages
what is the role of glycogen synthase
- Glycogen synthase adds glucose to the chain making 1-4 links
more complicatedly
- UDP-glucose has the enzyme glycogen synthase acts on it which takes the glucose of off UDP and adds it onto the glycogen chain this produces glycogen +1 and UDP
how is the glycogen chain extended and broken down chemically
- Start with glucose – 6 phosphate
- Move the phosphate from carbon 6 to carbon 1 producing glucose-1-phosphate this is a reversible reaction
- Energy is put in to the system via UTP (same type of thing as putting ATP in the system) this produces UDP attached to glucose and 2 phosphate groups joined together called PPi
- UDP-glucose has the enzyme glycogen synthase acts on it which takes the glucose of off UDP and adds it onto the glycogen chain this produces glycogen +1 and UDP
- Break down occurs through the enzyme of glycogen phosphorylase which produces glucose-1-phosphate and produces a glycogen chain which is 1 glucose less as it removes a glucose from glycogen
how do you control blood glucose levels (glycogen in the liver)
- Insulin increases glucose storage of liver and muslces – this is glycogen synthesis
- Glucagon – this releases glucose form the liver into the blood – breakdown of glycogen
how do you control glucose and glycogen levels in the muscles in order to provide energy to the muscles
- Adrenalin, calcium and contraction of muscle – cause glycogen breakdown to provide energy
when is glycogen synthase activated
- When glycogen synthase is in its phosphorylated from it is inactivated
- when it is dephosphorylated then it is activated
what causes dephosphroylation of glycogen synthase
- Dephosphorylation is promoted by insulin, this activates protein phosphatase-1 – when glucose is high in the blood insulin is released and therefore more protein phosphatase-1 is produced and glycogen synthase is activated by dephosphorylation
what causes phosphorylation of glycogen synthase
- Phosphorylation occurs by adrenaline in the muscles and glucagon in the liver, these control cAMP which controls protein kinase A and phosphorylase kinase which phosphorylates glycogen synthase and causes inactivation, this occurs when blood glucose is low, glucagon or adrenaline are released this causes cAMP to increase which increases protein kinas A and phosphorylase kinase which inactivates glycogen synthase by phosphorylating it
what is the allosteric effect
- there is the allosteric effect of glucose-6-phosphate - this can promote the action of glycogen synthase
what is the structure of PKA
made up of 4 subunits, 2 regulatory and 2 catalystic
what is glycogen breakdown triggered by
- This is stimulated by glucagon and adrenaline
describe how glycogen breakdown happens
- Glycogen phosphorylase breaks the 1-4 links by adding a phosphoryl group
- Glucose-1-phosphate can than be depohosphorylated by glucose-1-phosphatase into glucose-6-phsophate and further dephosphorylation to be exported as glucose if needed
when is glycogen phosphorylase activated
- This enzyme is phosphorylated, it is activated when it is phosphorylated and inactive when its dephosphorylated
what enzyme is the main control of the liver
glucagon
what is different about glycogen breakdown in the muscles versus in the liver
- in the muscles All breakdown leads to energy production in that cell only, it cannot be converted to glucose therefore cannot leave the cell and be transported
how does glycogen breakdown occur in the muscle
- Adrenaline via beta adrenergic receptor and glucagon via glucagon receptor activates adenylyl cyclase to convert ATP to cAMP
- cAMP activates protein kinase A which activates phosphorylase kinase and this activates glycogen phosphorylase causing glycogen to be broken down into glucose it also causes the inactivation glycogen synthase
- glucose-6-phsophate produced this goes into glycolysis
- glucagon and adrenaline increase cAMP
- cascade to convert glycogen
- insulin breaks down cAMP via phosphodiesterase preventing breakdown cascade therefore preventing the breakdown of glycogen
what is another work for breakdown of glucose
Glycogenolysis
what does insulin do to prevent breakdown of glycogen in the muscle
- insulin breaks down cAMP via phosphodiesterase preventing breakdown cascade therefore preventing the breakdown of glycogen
how is glycogen synthase and glycogen phosphorylase are consoled by reciprocal control
- The same enzymes will also phosphorylate glycogen synthase
- Glucagon and adrenaline turn on PKA, PKA phosphorylates glycogen synthase, This turns off glycogen synthase, And turns on breakdown by turning on glycogen phosphorylase
- Insulin turns on protein phosphoatase which dephophorylates glycogen phosphorylase and turns it off but it turns on glycogen synthase
what does insulin do
dephosphorylates glycogen synthesis, breakdown cAMP
what causes glycogen breakdown
increase in cAMP
what does glucagon adrenaline do
activates phosphorylates
describe an overview of glycogen metabolism disorders
- autosomal recessive disease effecting glycogen metabolism – glycogen storage diseases
- As the enzymes are expressed as different isoforms you get tissue specific effects
type I
- deficiency in
- consequence caused
deficiency in: - glucose -6-phosphatase
consequence: hypoglycaemia and lacicacidemina
type II
- deficiency in
- consequence caused
deficiency in: lysosomal glycogen breakdown
consequence: heart failure
type III
- deficiency in
- consequence caused
deficiency in: debranching enzyme
consequence: hypoglyceamia
type IV
- deficiency in
- consequence caused
deficiency in: branching enzyme
consequence:-
type V
- deficiency in
- consequence caused
deficiency in: muscle phosphorylase
consequence:exercise induced cramps and fatigue
type VI
- deficiency in
- consequence caused
deficiency in: liver phosphorylase
consequence: hypoglycaemia
describe type V McArdles and what they experience
- deficiency in muscle glycogen phosphorylase in muscle tissue
- liver glycogen phosphorylase is fine
- autosomal recessive
- patients struggle with exercise at first as the glycogen storage in provides energy for that individual muscle store
- people with this disease cant do intense exercise
- they can slowly build themselves into exercise and after a period of time called 2nd wind is when exercise becomes much easier
- avoid fast bursts – no more 6 seconds
- 1 in 100000
how do you diagnose type V McArdles
- Markers of muscle damage in blood/urine post intense exercise
- CK/myoglobin
describe type VI Her’s
- Deficiency in glycogen phosphorylase in liver
- They struggle with blood glucose between meals
- These people can exercise
what is the treatment for Her’s
- Why should glucagon a common treatment for hypoglycaemia not used – about getting glucose in the blood stream not glycogen
