glycogen metabolism

• Glycogen


  A readily mobilized storage form of glucose
• Glycogen


  • Liver: Can constitute up to 10% of the liver's weight
  • Muscle: Makes up 1-2% of muscle weight
  • Stored as large, hydrated granules (10-40 nm in diameter) in the cytoplasm
• Structural Features of Glycogen

  • Branched polymer of glucose residues
  • α(1→4) Glycosidic bonds connect most glucose units linearly
  • α(1→6) Glycosidic bonds create branches approximately every tenth residue
  • Branching increases the solubility of glycogen and creates numerous terminal residues for rapid synthesis and degradation
• Glycogen Degradation (Glycogenolysis)


  1. Release of Glucose-1-Phosphate (G1P)

  2. Remodeling of Glycogen

  3. Conversion of G1P to G6P
• Glycogen Phosphorylase


  Enzyme that cleaves α(1→4) bonds at nonreducing ends of glycogen, releasing G1P
• Debranching Enzyme


  Enzyme with transferase and α(1→6) glucosidase activities that remodels glycogen
• Phosphoglucomutase


  Enzyme that catalyzes the reversible transfer of a phosphate group, converting G1P to G6P
• Glycogen Synthesis (Glycogenesis)


  1. Activation of Glucose

  2. Initiation of Glycogen Synthesis

  3. Elongation of Glycogen Chains

  4. Formation of Branches
• UDP-glucose pyrophosphorylase


  Enzyme that catalyzes the formation of UDP-Glucose from G1P and UTP
• Glycogenin


  Enzyme that acts as a primer, catalyzing the attachment of glucose residues to itself and forming a short chain of about 8 glucose residues
• Glycogen Synthase


  Enzyme that transfers glucose residues from UDP-glucose to the nonreducing end of glycogen, forming α(1→4) glycosidic bonds
• Branching Enzyme (amylo(1→4) to (1→6) transglycosylase)


  Enzyme that introduces α(1→6) branches by transferring a segment of about 7 glucose residues from the end of a glycogen chain to an internal position, forming a branch point
• Phosphorylase Kinase (activated by glucagon and adrenaline)


  Converts phosphorylase b (less active) to phosphorylase a (more active)
• Phosphorylase a Phosphatase (PP1)

  Converts phosphorylase a back to phosphorylase b
• PP1


  Dephosphorylates glycogen synthase b (inactive), converting it to glycogen synthase a (active)
• Glycogen Synthase Kinase 3 (GSK3) and Protein Kinase A (PKA)


  Phosphorylate glycogen synthase a, converting it to the inactive glycogen synthase b
• Insulin signaling


  Inhibits GSK3, promoting glycogen synthesis by maintaining glycogen synthase in its active form
• Glycogen Storage Diseases


  • Von Gierke's Disease: Deficiency in glucose-6-phosphatase, leading to impaired glycogenolysis and gluconeogenesis
  • McArdle's Disease: Deficiency in muscle phosphorylase, leading to impaired glycogen degradation in muscle
• Glycogen phosphorylase is the key enzyme for glycogen degradation regulation
• The reaction catalyzed by glycogen phosphorylase produces glucose-1-phosphate (G1P)
• Glycogen synthase is the main enzyme involved in glycogen synthesis
• The activated form of glucose used by glycogen synthase is UDP-glucose