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• Glycogen


  A highly branched polymer of glucose residues that serves as a store of glucose to maintain blood [glucose] by the liver and for energy generation (muscle)
• Glycogen


  • Glucose requires hydration so unsuitable for storage
  • Stored as insoluble granules in the liver (up to 10% w/w ~100g) and in skeletal muscle (up to 2% w/w ~400g)
• Uses of glycogen


  • Glucose export to blood for other tissues
  • Glycolysis
  • Pentose phosphate pathway
• Fatty acids cannot be metabolised anaerobically
• Blood glucose must be maintained to serve as fuel for the brain
• Animals cannot convert fatty acids to glucose
• The glyoxylate pathway is only an option if you are a plant or a bacteria
• Glycosidic bonds


  Two types of glycosidic bonds in glycogen
• Phosphorolytic cleavage of glycogen


  1. Catalysed by glycogen phosphorylase

  2. α-1,4 glycosidic bonds on each branch are cleaved till 4 residues left

  3. Transferase shifts a block of 3 residues from one branch to the other

  4. The branch point residue (green) is removed by α-1,- glycosidase (debranching enzyme) leaving a linear chain
• Glycogen breakdown does not occur by a "reversal" of the phosphorolytic cleavage
• Glycogen synthesis


  1. Requires input of energy

  2. Coupling to UTP cleavage forming uridine diphosphate glucose (UDPG)

  3. Catalysed by UDPG pyrophosphorylase

  4. Catalysed by glycogen synthase forming new α-1,4 glycosidic bond
• Glycogenin


  The glycogen primer consists of four or more α-1,4 linked glucose residues attached to a tyrosine in the protein
• Branching enzyme


  Transfers blocks of ~ 7 glucose residues to interior sites and attaches the α-1,6 linkages
• Patients with ANDERSEN'S DISEASE lack the branching enzyme and usually die of liver failure at an early age
• Formation and breakdown of glycogen


  1. Glucose-6-P

  2. Glucose-1-P

  3. UDP-Glucose

  4. UTP

  5. PP_i

  6. Glycogen

  7. Glycogensynthase

  8. Glycogenphosphorylase
• If both the glycogen synthesis and breakdown reactions run at the same time we have a futile cycle
• Glycogenphosphorylase and glycogensynthase


  Are reciprocally regulated
• Hormones regulating glycogen metabolism


  • Breakdown: glucagon and adrenaline
  • Synthesis: Insulin
• Regulation of glycogen metabolism

  • Enzymes are regulated via phosphorylation
  • Also allosteric regulation by effectors signaling energy state of the cell
• Epinephrine (adrenaline) signal


  Has opposite effects on glycogen synthesis and breakdown
• Phosphorylase


  • Activated by phosphorylation
  • Glycogen synthase is inactivated by phosphorylation
• Low blood glucose


  Low insulin, glucagon release, phosphorylase activation and glycogen synthase inactivation, glycogen breakdown
• High blood glucose


  High insulin, low adrenalin and glucagon, glycogensynthase activation and phosphorylase inactivation, glycogen synthesis
• Phosphorylase


  • Exists as a homodimer in relaxed (R) or tense (T) states
  • Phosphorylated relaxed state is ACTIVE
  • Dephosphorylated tense state is INACTIVE
• Muscle phosphorylase b


  Usually inactive, allosterically activated by AMP and inhibited by ATP and G-6-P
• Liver phosphorylase


  The binding of glucose to phosphorylase a shifts the equilibrium to T state, inactivating the enzyme
• Isozymes


  Multiple forms of an enzyme that catalyze the same reaction but differ from each other in their primary structure, kinetic properties and allosteric regulation, often originating from gene duplication
• Control of blood [glucose] by pancreatic secretions


  High blood [glucose] leads to insulin release, low blood [glucose] leads to glucagon release
• Fasting


  Glucagon release from pancreas
• Stress, exercise


  Epinephrine release from adrenal medulla
• Mobilisation of glucose


  1. Liver: Glycogen breakdown, gluconeogenesis

  2. Muscle: Glycogen breakdown, lactate production
• The Cori cycle is important for maintaining blood glucose levels
• Glycogen metabolism is key to maintaining blood glucose levels
• Synthesis and breakdown of glycogen are reciprocally regulated to avoid a futile cycle
• Organs work together to maintain adequate glucose and respond to need for ATP
• Key hormones regulating glycogen metabolism


  • Glucagon
  • Adrenaline
  • Insulin