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Glycogen

Uni of Notts, Signalling & Metabolic Regulation, Year 2, Topic 9

TermDefinition
Glycosidic bonds in glycogen α(1→4) bonds form linear chains & α(1→6) bonds form branch points
Non-reducing ends & why glycogen has so many terminal points of the glycogen polymer without exposed C1 on glucose (i.e., branches or end of chain). They allow multiple glycogen phosphorylase enzymes to act simultaneously for rapid glucose release
How muscle & glycogen stores differ & their roles Liver: ~100g (10% mass), maintains blood glucose during fasting over hours. Muscle: ~400g (2% mass), fuels muscle contraction during exercise for around 30 minutes of intense exercise
Role of glycogen in the brain Small astrocyte glycogen stores (~0.5–1.5g) provide emergency energy during high neuronal demand
Glycogen phosphorylase Begins glycogenolysis by removing glucose from non-reducing ends via phosphorolysis using orthophosphate to produce G1P
Why phosphorolysis is energetically favourable Relatively small -ΔG so requires [Orthophosphate]/[glycogen] = ~100x to drive the reaction
Phosphoglucomutase Converts G1P → G6P via a phosphoserine intermediate which converts it to 1,6-bisphosphate then accepts phosphate from C1
3 fates of liberated G6P Glycolysis, pentose phosphate pathway, or glucose release in liver
Glucose-6-phosphatase Hydrolyses phosphate on G6P to release free glucose into the liver, only exists in the liver so muscles can't undergo gluconeogenesis to release glucose into the blood
Why debranching is required during glycogenolysis Glycogen phosphorylase stops near branch points & cannot cleave α(1→6) bonds
Glycogen Debranching Enzyme Transfers a glucose trimer & hydrolyses the remaining α(1→6)-linked glucose to release as free glucose (compared to the others which are released as G1P
G1P activation G1P reacts with UTP to form UDP-glucose, making glycogen synthesis energetically favourable
How UDP-glucose formation is driven Pyrophosphate produced from UTP is hydrolysed, making the reaction irreversible
Glycogenin A primer protein that autoglucosylates itself to initiate glycogen synthesis
Glycogen synthase Forms α(1→4) glycosidic bonds to elongate glycogen chains
Glycogen branching enzyme & why it's needed Creates α(1→6) branches by transferring glucose segments to increase solubility by preventing tight packing which increases enzyme accessibility to provide instant energy supply
How muscle glycogen phosphorylase is allosterically regulated Activated by AMP & Ca²⁺ (B to A/T to R form); inhibited by ATP & G6P
How liver glycogen phosphorylase respond to glucose ~90% homology to muscle but 2 glucose promotes conversion from active phosphorylase a → inactive b form
How adrenaline stimulates glycogen degradation Activates GPCR → cAMP → PKA signalling cascade to phosphorylate glycogen phosphorylase to A form & catalyse phosphorolysis
Why glycogen synthesis & breakdown don't occur simultaneously Reciprocal regulation ensures one pathway is active while the other is inhibited by overall changing phosphorylation states of glycogen phosphorylase
PP1 Protein Phosphatase 1. Dephosphorylates enzymes to activate glycogen synthase & inhibit glycogen breakdown
How insulin stimulates glycogen synthesis Activates PP1, promoting glycogen synthesis & inhibiting glycogenolysis
Phosphorylase kinase Heterotetramer in the liver. Activates glycogen phosphorylase by converting phosphorylase b → a or T → R. Has constitutive function
How phosphorylase kinase is activated Partially activated by phosphorylation of α or β subunits by PKA or by Ca²⁺ binding to the calmodulin δ regulatory subunit but fully activated when both happen at the same time
Created by: Denny12
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