Glycogen

• Glycogen


  Storage form of glucose in animals

  
• Glycogen


  • Stored in liver (6-8%) and muscle (1-2%)
  • Helps to maintain the blood glucose levels between meals
  • Glycogen stores increase in a well-fed state, depleted during fasting
  • Muscle glycogen serves as a fuel reserve for the supply of ATP during muscle contraction

  
• Glycogenesis


  Synthesis of glycogen from glucose which occurs in liver and muscle

  
• Glycogenesis


  1. Glucose converted to glucose-6-phosphate

  2. Glucose-1-phosphate formed

  3. UDPG (uridine diphosphate glucose) is the carrier of glucose

  4. Glucose from UDPG is attached at the nonreducing end of glucose molecules of glycogen primer

  
• Glycogenin


  Protein that can accept glucose from UDPG to form initial glucose primer

  
• Glycogen branching


  Branching enzyme (Amylo 1,4 –1,6 transglucosidase) transfers 6 glucose residues portion from one chain to a neighbouring chain to form a -1,6 – linkage

  
• Glycogenolysis


  Breakdown of glycogen to glucose

  
• Glycogenolysis


  1. Phosphorylase phosphorolytically splits -1,4 glucoside bonds from the outermost chains of glycogen until 4 residues remain on either side of – 1.6 branch point

  2. 1.4 glucan transferase transfers 3 glucose residue portion from one side chain to the other exposing -1,6 branch points

  3. Amylo 1, 6 glucosidase splits the 1,6 linkages

  4. Acid maltase or -1,4-glucosidase (lysosomal enzyme) degrades small quantity of glycogen

  
• Muscle glycogenolysis


  Glycogen -> Glucose-1-P -> Glucose-6-P -> glycolysis -> lactate

  
• Glycogen synthase


  Exists in active and inactive forms, dephosphorylated form is active
• Glycogen phosphorylase


  Exists in active and inactive forms, phosphorylated form is active
• High cAMP level


  Activates phosphorylase, inactivates glycogen synthase
• Glucose-6-phosphate, ATP, glucose


  Allosterically inhibit phosphorylase

  
• Glucose-6-phosphate


  Activates glycogen synthase

  
• Regulation of glycogenesis and glycogenolysis

  1. Adrenaline and glucagon activate adenylate cyclase, increasing cAMP

  2. cAMP activates protein kinase, which phosphorylates and activates phosphorylase kinase

  3. Phosphorylase kinase phosphorylates and activates phosphorylase, leading to glycogenolysis

  4. Insulin activates phosphodiesterase, decreasing cAMP, leading to glycogenesis
• Glycogen storage diseases


  • Genetic diseases with deposition of abnormal type or increased quantity of glycogen in tissues
• Glycogen storage diseases


  • Type I: Glucose-6-phosphatase deficiency (Von Gierke's disease)
  • Type II: Lysosomal α-1,4-glucosidase deficiency (Pompe's disease)
  • Type III: Debranching enzyme deficiency (Limit dextrinosis/Cori's disease)
  • Type IV: Branching enzyme deficiency (Andersons disease)
  • Type V: Muscle glycogen phosphorylase deficiency (McArdle's disease)
  • Type VI: Liver glycogen phosphorylase deficiency (Hers disease)

  
• Von Gierke's disease


  • Accumulation of glycogen in liver, hypoglycemia, ketosis, lactic acidemia, hyperlipidemia, hyperuricemia, liver enlargement, failure to grow