Glycogen Storage Diseases Lecture Notes

Overview

• Focus on glycogen storage diseases, crucial for USMLE and COMLEX exams.
• Key processes: Glycogenolysis (glycogen breakdown) vs Glycogenesis (glycogen synthesis).
• Understanding biochemistry crucial for disease context.

Glycogenesis vs Glycogenolysis: Biochemistry

• Glycogenesis:
  • Begins with glucose-6-phosphate from glycolysis.
  • Key enzymes: Phosphoglucomutase, UDP-glucose pyrophosphorylase, Glycogen synthase.
  • Creates alpha 1-4 linkages, branches via alpha 1-6 linkages by branching enzyme.
• Glycogenolysis:
  • Glycogen phosphorylase converts glycogen to glucose-1-phosphate.
  • Debranching enzyme required for breaking alpha 1-6 bonds.
  • Involves conversion back to glucose-6-phosphate and then free glucose.

Rate-Limiting Enzymes

• Glycogen synthase: Glycogenesis pathway, activated by insulin.
• Glycogen phosphorylase: Glycogenolysis pathway, activated by glucagon.
• Opposing enzyme activity: One's activation inhibits the other.

Glycogen Storage Diseases

Von Gierke Disease (Von Geek Disease)

• Deficiency: Glucose-6-phosphatase.
• Symptoms: Hepatomegaly, hypoglycemia, hyperlipidemia, hyperuricemia.
• Mnemonic: "Fat geek" - big liver (hepatomegaly), high fat and uric acid levels.

Cori Disease (Coral Disease)

• Deficiency: Debranching enzyme (alpha 1-6 glucosidase).
• Symptoms: Similar to Von Gierke but with abnormal glycogen structure.
• Mnemonic: "Coral reef" - highly branched glycogen.

McArdle's Disease

• Deficiency: Glycogen phosphorylase in muscle.
• Symptoms: Muscle cramps, exercise-induced hypoglycemia, myoglobinuria.

Hers Disease

• Deficiency: Glycogen phosphorylase in liver.
• Symptoms: Hepatomegaly, fasting hypoglycemia.
• Mnemonic: M2M (muscle for McArdle's), HDH (hepatic for Hers).

Anderson Disease

• Deficiency: Branching enzyme.
• Symptoms: Cirrhosis due to long straight glycogen chains.
• Mnemonic: "Anderson Cooper - gets straight to the point."

Pompe Disease

• Deficiency: Lysosomal debranching enzyme.
• Symptoms: Cardiomegaly, hypertrophic cardiomyopathy.
• Mnemonic: "Pompe affects the pump" - heart is the pump.
  • Analogy to Mt. Vesuvius - buildup and explosion.

Summary

• Diseases correlated with specific enzyme deficiencies.
• Visual diagram format: Enzymes in red, rate-limiting enzymes bolded, diseases in purple.
• Arrows and color codes for glycogen synthesis (blue) and breakdown (green).
• Important to understand enzyme roles and regulation for disease context.