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Glycogen metabolism, Draw out - Coggle Diagram
Glycogen metabolism
Glycogen structure
Polymer of \(\alpha\)-D glucose
Main chain is simple glucose molecules
Linked by \(\alpha\) 1-4 linkages
i.e. glycosidic bond between carbon 1 + 4 of 2 glucose molecules
Main chain contains branches
Linked to main chain by \(\alpha\) 1-6 linkages
i.e. glycosidic bond between carbon 1 + 6 of 2 glucose molecules
Occur every ~8-12 residues of main branch
Highly branched molecule
Much more soluble
Increases number of non-reducing ends so more UDP-glucose can be added
Single molecule may contain up to 50,000 glucose residues
Seen in cytoplasm as dark granules
Granules contain all enzymes needed for synthesis + degradation
Covalently linked to glycogenin protein
Regulation
Reciprocally regulated
In liver
Fed state
Glycogenesis
Fasting state
Glycogenolysis
In muscle
Active
Glycogenolysis
Resting
Glycogenesis
Controlled via 2 enzymes
Glycogen synthase
Glycogen phosphoryase
Exists in 2 forms
Phosphorylated (active)
Dephosphorylated (inactive)
Equilibrium between 2 forms
Hormone regulation
Fasting state
Glucagon increases
Epinephrine from adrenal medulla
Release of cAMP
Activation of PKA
Phosphorylates
Glycogen phosphorylase kinase b
to active form (a)
Phosphorylates
Glycogen phosphorylase b
to active form (a)
Glycogen degraded
Activates inhibitor proteins that inhibit protein phosphatases that would reverse the reactions
Phosphorylates
Glycogen synthase
to inactive form
Glycogenesis inhibited
Active form of
glycogen synthase
is dephosphorylated (opposite to
glycogen phosphorylase
)
Second messenger signalling
Fed state
Release of insulin
Increases phosphatase activity
Leading to inactivation of
glycogen phosphorylase
Activation of
glycogen synthase
Epinephrine
Second messenger system
Adrogenergeic receptors
G protein-coupled receptors
Activate G proteins
Activating
phospholipase C
Activates PIP\(_2\)
Cleaves second messenger IP\(_3\)
1 more item...
Allosteric regulation
Glycogenesis stimulated when glucose + levels are high
Glycogenolysis stimulated when glucose + energy levels are low
Liver
G-6-P is important effector molecule
Allosterically activates
glycogen synthase
Allosterically inhibits
glycogen phosphorylase
Muscle
G-6-P
High levels of AMP activate phosphorylase
In exercising muscle
Anoxia
Release of Ca\(^{2+}\) in contracting muscle
4 Ca\(^{2+}\) bind to calmodulin (CaM)
Conformational change + CaM binds to
Glycogen phosphorylase kinase
Increases active form without need for PKA pathway
Glycogen synthesis
UDP-glucose needed
Produced from glucose 1-phosphate
Phosphoglucomutase
moves phosphate from C1 to C6 generating glucose 6-phosphate
Add UTP to produce
PP\(_i\) (Inorganic pyrophosphate)
Quickly cleaved to 2 x P\(i\) to prevent reverse reaction
UDP-glucose
Catalysed by
UDP-glucose pyrophosphorylase
Important enzyme
Glycogen synthase
Can only elongate existing chain of glucose - cannot create one
Initial chained formed from a primer
Adds UDP-glucose to non-reducing ends of developing glycogen chain
Glycogenin
Conserved tyrosine at position 194
Side chain of tyrosine has a hydroxyl group which adds the UDP-glucose
Primer for initial chain
Autoglycosylation
Self catalysing
Also catalyses at least 3 more additions of UDP-glucose
Forming branches
4:6 transferase
Forms \(\alpha\)1-6 glycosidic bonds from 1-4 bonds
Energetics
At
glycogen synthase
step
\(\Delta G^{o'}\)=-13.4kJ/mol
Whole process is exergonic
Glycogen degradation (glycogenolysis)
End products
Glucose
Can be phosphorylated into glucose-6-phosphate and fed into glycolytic pathway
Hexokinase/glucokinase
Glucose 1-phosphate
Phosphoglucomutase
Converted to G-6-P which can then be phosphorylated to glucose
Lysosomal degradation
~1-3% glycogen degraded in lysosomes
Lysosomal \(\alpha\)(1\(\rightarrow\)4) glucosidase
First enzyme
Glycogen phosphorylase
Main controller of glycogenoylsis flux
Regulation of pathway
Sequentially cleaves \(\alpha\)(1\(\rightarrow\)4) bonds at non-reducing ends
Until there are 4 glycosyl units on each branch point
Structure named limit dextrin at this point
Second enzyme
Debranching enzyme
4:4 transferase
activity
Remove outer 3 glycosyl residues in a branch
Transfer them to a non-reducing end
Extends main chain -
glycogen phosphorylase
continues
Bifunctional activity
Amylo-\(\alpha(1\rightarrow6\))-glucosidase
activity
Removes \(\alpha(1\rightarrow 6\)) bonds hydrolytically
Steps of degradation are repeated until all is degraded
Maintenance of blood glucose
Diet
Glycogen
Stored form of glucose
Stored in liver + muscle
Can be rapidly degraded to glucose for tissue + bloodstream
Gluconeogenesis
Draw out