Carbohydrate Metabolism: Glycogenesis and Glycogenolysis Flashcards Preview

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Flashcards in Carbohydrate Metabolism: Glycogenesis and Glycogenolysis Deck (17)
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1

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

2

Why is [glucose] kept around 5mM

Ideal for transport across blood- brain barrier

3

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

4

3 enzymes involved in glycogen degradation

1) Glycogen phosphorylase
2) Glycogen debranching enzyme
3) Phosphoglucomutase

5

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

6

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

7

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

8

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

9

How is Phosphoglucomutase involved in both glycogen synthesis and degradation?

- Catalyses both G1P G6P
- Depending on conc both
- goes either way to restore equilibrium

10

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

11

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

12

What 2 enzymes are tightly regulated in glycogen systhesis and degradation

- synthesis= glycogen synthase
- degradation= glycogen phosphorylase

13

What 2 types of regulation do glycogen synthase and phosphorylase undergo?

- hormonal regulation (via phosphorylation/ dephosphorylation)
- allosteric regulation

14

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

15

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

16

Ca as an allosteric regulator of muscle glycogen phosphorylase- how does this work?

- Ca released from SR into sarcoplasm causing contraction
- Ca binds to the calmodulin protein- small subunit of phosphorylase kinase
- Activates conplex b--> a
- Phosphorylase kinase activates
glycogen phosphorylation through phosphorylation
- Breaking down glycogen

17

What are glycogen storage diseases

- caused by genetic defect in enzyme required for glycogen synthesis or degradation leading to accumulation of glucose or abnormal structure
- May lead to hypoglycaemia as unable to utilise current glycogen stores e.g. type 1 G6Pase not present so cannot be converted to glucose and transported out of liver--> hypoglycaemia