A muscle biopsy from a patient with exercise intolerance and myoglobinuria after vigorous activity shows absent myophosphorylase on histochemical staining (McArdle disease). Serum lactate fails to rise during ischemic forearm exercise, but ammonia rises appropriately. This dissociation occurs because:
- A AMP deaminase is activated during exercise generating ammonia from adenylate, while glycogen-derived glucose-1-phosphate cannot enter glycolysis to produce lactate ✓
- B Ammonia is produced by protein catabolism, which is unaffected by myophosphorylase deficiency
- C Ammonia derives from glutamine hydrolysis in the liver, which is independent of muscle glycogenolysis
- D Lactate is converted to glucose in the Cori cycle, masking any rise
Correct answer: A. AMP deaminase is activated during exercise generating ammonia from adenylate, while glycogen-derived glucose-1-phosphate cannot enter glycolysis to produce lactate
Explanation
In McArdle disease, myophosphorylase is absent so glycogen cannot be mobilized to glucose-1-phosphate; consequently glycolysis is substrate-limited and lactate does not rise during ischemic exercise. However, with exercise, the energy demand leads to AMP accumulation in muscle, and AMP deaminase (myoadenylate deaminase) converts AMP to IMP with release of ammonia — this pathway is intact in McArdle disease. The ischemic forearm exercise test thus shows a normal ammonia rise with a flat lactate response, which is the diagnostic hallmark.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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