Lecture Notes: Glycogen Storage Diseases

Overview

• Focus on glycogen storage diseases, important for USMLE and COMLEX exams.
• Discuss the biochemistry of glycogen synthesis (glycogenesis) vs. glycogen breakdown (glycogenolysis).

Biochemistry

Glycogenesis (Glycogen Synthesis)

• Pathway Initiation: Begins with glucose 6-phosphate from glycolysis.
• Steps:
  1. Glucose 6-phosphate converted to glucose 1-phosphate by phosphoglucomutase.
  2. Glucose 1-phosphate converted to UDP-glucose by UDP glucose pyrophosphorylase.
  3. UDP-glucose to glycogen by glycogen synthase (Rate-limiting enzyme).
• Regulation:
  • Activated by insulin.
  • Branching enzyme creates alpha 1-6 linkages to prevent linear growth and toxicity.

Glycogenolysis (Glycogen Breakdown)

• Pathway:
  • Glycogen converted to glucose 1-phosphate by glycogen phosphorylase (Rate-limiting enzyme).
  • Glucose 1-phosphate to glucose 6-phosphate, then free glucose.
• Regulation:
  • Activated by glucagon.
  • Debranching enzyme cuts alpha 1-6 bonds for glucose release.

Key Enzymes

• Glycogen Synthase: Rate-limiting in synthesis.
• Glycogen Phosphorylase: Rate-limiting in breakdown.
• Branching Enzyme: Forms alpha 1-6 linkages.
• Debranching Enzyme: Cuts alpha 1-6 bonds.
• Glucose-6-Phosphatase: Converts glucose 6-phosphate to free glucose.

Glycogen Storage Diseases

Von Gierke Disease

• Deficiency: Glucose-6-phosphatase.
• Symptoms: Hepatomegaly, hypoglycemia, hyperlipidemia, hyperuricemia.
• Mnemonic: "Von Geek" - Fatty liver and poor muscle structure.

Cori Disease

• Deficiency: Debranching enzyme.
• Symptoms: Similar to Von Gierke, plus abnormal glycogen structure.
• Mnemonic: "Coral Reef" - Highly branched glycogen structure.

McArdle’s Disease

• Deficiency: Glycogen phosphorylase in muscle.
• Symptoms: Muscle cramps, myoglobinuria, hypoglycemia on exertion.
• Mnemonic: M2M (muscle for McArdle’s).

Hers Disease

• Deficiency: Glycogen phosphorylase in liver.
• Symptoms: Hepatomegaly, fasting hypoglycemia.
• Mnemonic: HDH (hepatic for Hers).

Anderson Disease

• Deficiency: Branching enzyme.
• Symptoms: Cirrhosis due to long-chain glycogen.
• Mnemonic: "Anderson Cooper" - Straight to the point, single-line glycogen.

Pompe Disease

• Deficiency: Debranching enzyme in lysosomes.
• Symptoms: Cardiomegaly, fatal condition due to heart involvement.
• Mnemonic: "Pompe affects the pump" - Heart is the pump.

Summary

• Enzymes in red, rate-limiting enzymes bolded.
• Diseases in purple, pathways highlighted with arrows (blue for synthesis, green for breakdown).
• Understanding biochemistry crucial for diagnosis and differentiating between diseases.