Carbohydrate Metabolism: Glycogenesis and Glycogenolysis Flashcards
How can we get glucose
- from diet
- from broken down stores in liver and muscle (glycogenolysis)- exhausted after 18hrs
- from gluconeogenesis if stores in liver run out- occurring in the liver and kidney
Why is [glucose] kept around 5mM
Ideal for transport across blood- brain barrier
Glycogen structure
Branched- makes breaking down easily and storage
Monosaccharides joined by a 1-4 glyosidic linkage- form MAIN CHAIN
About every 8 monosaccharides- branching point- a1-6 linkage being formed
Reducing/ non-reducing ends found- want electrons/ donate electrons
1 reducing end and many non-reducing ends found on the end on each branch
- evolved to permit max release of glucose units from non-reducing ends
Glycogen molecule contains all enzymes to synthesise and break glycogen down
Adapted for efficient store/ release
3 enzymes involved in glycogen degradation
1) Glycogen phosphorylase
2) Glycogen debranching enzyme
3) Phosphoglucomutase
Explain role of the 3 enzymes involved in glycogen breakdown
1) Glycogen phosphorylase (dimer)- chops up main chain breaking 1-4 glycosidic bonds creating glucose1-phosphate until 4 glycosyl units away from branching point (30 angstroms) as this is the distance between active site and substrate binding site- and crevice wont permit branch region to fit in so this gets stuck-
- bunch of 4 glycosyl units= limit dextrin
- requires coenzyme pyridoxal 5 phosphate (from vitamin B6)
- undergoes allosteric interactions causing covalent modification:
- inhibited by ATP, G6P, glucose
- activated by AMP
- undergoes conformational change from tense to relaxed state and active site is revealed
2) Glycogen debranching enzyme- bifunctional: acts as a 1,4 transglycosylase and amylo-a 1,6 glucosidase (as makes amylase)
- on limit dextrin breaks 1-4 glycosidic bond between 3rd and 4th glycosyl unit
Makes 1,4 glycosyl bond with non- reducing end (main chain)
- Breaks remaining glucosyl unit by breaking 1,6 glyosidic bond creating free glucose
3) Phosphoglucomutase- converts G1P to G6Pto continue along glyosidic or pentose phosphate pathway
Which is the slowest enzyme involving the breakdown of glycogen and how is glycogen adapted for this
Glycogen debranching enzyme:
- Not too many branches so not too dense for enzymes to act/ move in
- Length of chains aren’t long enough to prevent activity of enzymes
- Not too many branches so glycogen debranching enzyme doesn’t do job too often - slow
optimal structure
Why is glucose 6P so important?
- converted to glycogen
- converted to glucose
- converted to ribose 5- phosphate
- converted to pyruvate–> CoA –> citric acid cycle
- or pyruvate forma aa or lactate
Explain enzymes involved in glycogen synthesis
- also Phosphoglucomutase which G6P–> G1P
- to put the G1P together we need a primer
- UDP glucose phosphorylase binds G1P to UDP to make UDP- glucose
- Formation of pyrophosphate drives this reaction
- glucose will stick to glycogenin releasing UDP
- Glycogenin will create a primer of up to 7 glycosyl units(primer)- getting each glucose from UDP glucose
- Glycogen synthase will then take over and create main chain of glucose catalysing the 1-4 glyosidic linkages- creating amylose
- Glycogenin remains attached to the reducing end of glycogen molecule
- Branching enzyme- 4-6 transferase activity- (amylo- 1,4-1,6 transglycosylase) takes chunk of a 1-4 bond in main chain and will attach it using 1-6 a bonds at about 8 glycosyl units in (hence branching regularly found at this interval)- creates glycogen
How is Phosphoglucomutase involved in both glycogen synthesis and degradation?
- Catalyses both G1P G6P
- Depending on conc both
- goes either way to restore equilibrium
How is glycogen phosphorylase regulated?
- inhibited by ATP, G6P, glucose
- activated by AMP
- undergoes conformational change from tense to relaxed state and active site is revealed
What happens in the liver and muscle during well fed and fasting periods/ exercise
Liver: In well-fed periods glycogenesis occurs, glycogenolysis occurs during fasting
Skeletal muscle: glycogenesis- rest periods
Exercise- glycogenolysis
What 2 enzymes are tightly regulated in glycogen systhesis and degradation
- synthesis= glycogen synthase
- degradation= glycogen phosphorylase
What 2 types of regulation do glycogen synthase and phosphorylase undergo?
- hormonal regulation (via phosphorylation/ dephosphorylation)
- allosteric regulation
Outline hormonal regulation of glycogen metabolism
- glycogenolysis: adrenaline (liver and muscle)/ glucagon (liver)- hormones bind to G- coupled receptor
- activate adenyl cyclase so cAMP is produced
- activates cAMP- dependent protein kinase A
- phosphorylates glycogen phosphorylase kinase b (inactive–> glycogen phosphorylase kinas A (active)
- this phosphorylates glycogen phosphorylase making the active glycogen phosphorylase a (active)
- Insulin acts on protein phosphorylase- removes P group inactivating glycogen phosphorylase
- activating glycogen breakdown
Glycogenesis: unlike glycogen phosphorylase glycogen synthase in inactive when phosphorylated- therefore same pathway - G coupled protein
- adenyl cyclase producing cAMP
- cAMP dependent kinase becomes activates
- BUT phosphorylation glycogen synthase
- Hence inactive
- Glycogen synthesis inhibited
Outline allosteric regulation of glycogen synthase and phosphorylase
- Glycogen synthase- activated by G6P in liver and muscle
- glycogen phosphorylase- inhibited by G6P and ATP (also glucose in liver)
- activated in muscle by AMP and Ca
- in high energy state high [glucose] [G6P] and [ATP] so GS activated and GP inhibited
- synthesis predominates
- low energy state: [Glucose], [G6P], [ATP] low [AMP] high - muscle glycogen phosphorylase activated by AMP
- degradation predominates
