Regulation of Glycogen metabolism
6 important questions on Regulation of Glycogen metabolism
How is glycogen metabolism regulated?
- control from outside the cell by (de)phosphorylation
Metabolites: AMP/ATP, glucose 6-phosphate, glucose
- control from within the cell by allosteric regulation
What is the difference between GP a and b?
- a: active state → phosphorylated phosphorylase
- b: less-active state → dephosphorylated phosphorylase
Both the a and b forms of GP can exist in the relaxed (R) state or tense (T) state.
- R (active) state → blue line is not blocking the active site
- T (inactive) state → blue line is blocking the active site
In which organs are the 2 isozymes of GP and what is their difference?
Liver phosphorylase
- has only a form and undergoes the R to T transition in the presence of glucose (inactivating it)
- acts as a glucose sensor when glucose binds it tells the GP to stop glycogen breakdown
Muscle phosphorylase
- a low energy charge (high AMP, low ATP) favours the transition of R (active) state
- a high concentration of ATP or glucose 6-phosphate favours transition of T (inactive) state
- calcium and adrenaline are hormones which react in muscle
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How is the glycogen synthesis and breakdown regulated (enzymes)?
Explain the regulation of Glycogen synthase by protein phosphatase 1 (PP1) in muscle and liver
- the catalytic subunit PP1 is bound to the regulatory subunit, Gliver
- Glucose brings GP in the T (inactive) state, allowing PP1 to dephosphorylate and inactivate GP
- Free PP1 inactivates GP but activates GS (eaten/insulin)
Muscle (during exercise or fasting)
- the catalytic subunit PP1 is active while bound to the regulatory subunit, Gmuscle
- PKA phosphorylates Gmuscle, such that PP1 is releaed and becomes less active
- PKA also phosphorylates and activates an inhibitor of PP1
- under these condition, GP and GS can shift to the phosphorylated form
- GP active
- GS inactive
What are the 6 glycogen storage diseases and due to which enzyme?
- Von Gierke: glucose 6-phosphatase (liver, kidneys)
- Pompe: alfa-(1,4)-glucosidase (all organs)
- lysosome full of glycogen
- Cori: debranching enzyme (muscle, liver)
- Andersen: branching enzyme (liver, spleen)
- McArdle: glycogen phosphorylase (muscle)
- Hers: glycogen phosphorylase (liver)
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