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Flashcards in Glycogen & HMP Shunt Deck (13)
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Structure of glycogen

  • Highly branched polymer of glucose monomers


Locations of glycogen in body

  • Liver
    • 20%, 100g
  • Muscle
    • 80%, 400g


Importance of glycogen structure

  • Represents pool of stored glucose that can be rapidly mobilized
  • Increases amount of glucose available between meals


Location of glycogen synthesis in body

  • Most prominent in:
    • Liver
    • Skeletal muscles


Glycogen synthesis pathway

  • Utilizes uridine diphosphate (UDP-glucose)
    • Activated form of glucose
    • Synthesized from G1P and UTP
    • Not G6P or G1P 
  • First step: conversion of G6P to G1P
    • Enzyme: phosphoglucomutase
  • Glycogen synthase catalyzes transfer of UDP-glucose to growing chain: IMPORTANT REACTION
    • Key regulated enzyme in glycogen synthesis
    • Can add glucose residues only if polysaccharide chain has been initiated and already contains more than 4 glucose residues
  • Branching enzyme forms a-1,6-linkages
    • Glycogen synthase adds glucose until 11 units are reached
    • Then branching occurs - 6-7 glucose residues transferred to internal site
    • Increases the solubility of glycogen
    • Effectively increases rate of synthesis and breakdown



Glycogen breakdown pathway (glycogenolysis)

3 steps:

  • 1. Release of glucose-1-phosphate from glycogen.
  • 2. Remodeling of glycogen substrate to permit further degradation.
  • 3. Conversion of glucose-1-phosphate into glucose-6-phosphate for further degradation

3 enzymes:

  • Glycogen phosphorylase** - key regulated enzyme in glycogenolysis
  • Debranching enzyme
  • Phosphoglucomutase


Reactions catalyzed by glycogen phosphorylase

  • Catalyzes phosphorolytic cleavage of glycogen into glucose-1-phosphate.
  • Phosphorylase is key regulatory enzyme in glycogenolysis.
  • Key reaction:
    • Glycogen (n residues) + Pi --> Glucose-1-phosphate + Glycogen (n-1 residues)


Reactions catalyzed by glycogen synthase

  • Catalyzes transfer of glucose from UDP-glucose to growing glycogen chain.
  • Activated UDP-glucose transferred to hydroxyl group at C-4 terminus of glycogen to form a-1,4 glycosidic linkage.
  • Key regulated enzyme in glycogen synthesis.
  • Can add glucose residues ony if polysaccharide chain has been initiated and already contains more than 4 glucose residues


Coordinate regulation of glycogenesis/glycogenolysis

  • Both regulated by hormones: insulin and glucagon
  • Regulate the activity of key enzymes through reversible phosphorylation


Metabolic conditions favoring glycogen synthesis

  • When substrate availability and energy levels are high
  • Occurs in liver when body is well fed
  • Occurs in skeletal muscle as soon as muscle is at rest


Metabolic conditions favoring glycogenolysis

  • When energy levels and glucose supplies are low
  • Occurs in liver during periods of fasting
  • Occurs in skeletal muscle during active exercise


Stimuli of glycogenolysis

  • Glucagon or epinephrine binding to receptors signals need for glycogen to be degraded to either elevate blood glucose or provide energy for exercising muscle
  • Calcium release in cell during muscle contraction
  • AMP


Stimuli of glycogen synthesis

  • Glycogen synthase = crucial.
  • When phosphorylated by glycogen synthase kinase (GSK) it is deactivated.
  • Likewise when dephosphorylated it is activated.
  • Enzyme managing dephosphorylation of glycogen synthase = protein phosphatase 1 (PP1).
  • G6P allosterically activates glycogen synthase when inactivated, making it a better substrate for PP1.
  • Insulin stimulates glycogen synthesis by dephosphorylating (and activating) PP1 which allows PP1 to dephosphorylate (and activate) glycogen synthase.
  • Insulin also inactivates GSK