Glycogenolysis Lecture Notes

Overview

• Glycogenolysis: Process of breaking down glycogen into glucose
• Key Concept: Refer to glycogenesis as it is the reverse process
• Location in the body: Liver and muscles (focus on significant sites)
• Trigger: Low blood glucose levels (Hypoglycemia)
• State: Fasting state or post-absorptive state
• Hormones involved:
  • Glucagon
  • Epinephrine
  • Norepinephrine
  • (Additionally) Growth hormone, thyroid hormones

Key Enzymes in Glycogenolysis

1. Glycogen Phosphorylase

   • Cuts alpha-1,4 glycosidic bonds
   • Uses phosphates (from pyridoxal phosphate) to form glucose 1-phosphate

2. Debranching Enzyme

   • Alpha-1,4 Glucosidase activity: Cuts alpha-1,4 bonds near branch points
   • Transfer activity: Moves three glucose units to a longer chain
   • Alpha-1,6 Glucosidase activity: Breaks alpha-1,6 bonds releasing free glucose

Process Steps

1. Glycogen Phosphorylase Action

   • Cuts alpha-1,4 glycosidic bonds between glucose units
   • Generates multiple glucose-1-phosphate molecules
   • Limited by proximity to alpha-1,6 branches

2. Debranching Enzyme Action

   • Cuts alpha-1,4 bond next to alpha-1,6 branch point
   • Transfers 3 glucose molecules to another chain
   • Breaks alpha-1,6 bond to release free glucose

3. Conversion and Transport

   • Glucose 1-phosphate is converted to glucose 6-phosphate by phosphoglucomutase
   • Glucose 6-phosphatase in the liver (not muscles) removes phosphate to form free glucose
   • Free glucose is released into blood to restore glucose levels

Additional Details

• Pyridoxal Phosphate involved in transferring phosphates (Vitamin B6 derivative)
• Glucose-6-Phosphatase
  • Present in liver, kidneys, and parts of the GI tract
  • Converts glucose 6-phosphate into free glucose for blood release
  • Not present in muscles, thus muscle glycogen does not directly contribute to blood glucose

Muscle Glycogenolysis

• Muscles lack glucose-6-phosphatase
• Glycogen breakdown stops at glucose 6-phosphate
• Contributes to blood glucose indirectly via Cori cycle and glucose-alanine cycle (to be discussed in gluconeogenesis)

Conclusion and Next Steps

• Review of glycogenolysis process
• Future lecture: Regulation and clinical correlations related to enzyme mutations
• Important to refer to glycogenesis for understanding the reverse process

Diagrams and Visual Aids

1. Structure of glycogen polymer with glycosidic bonds
2. Enzyme mechanisms: Glycogen Phosphorylase and Debranching Enzyme
3. Pathways: Conversion of glucose-1-phosphate to glucose-6-phosphate to free glucose
4. Tissue-specific enzyme function (Glucose-6-Phosphatase presence)