A 28-year-old male with a history of recurrent muscle pain and myoglobinuria after exercise is found to have deficiency of phosphofructokinase (PFK). Which of the following best explains the biochemical basis of his symptoms?

Explanation

## Phosphofructokinase (PFK) Deficiency **Mechanism of Symptoms:** PFK catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, a committed and rate-limiting step of glycolysis. Deficiency of this enzyme blocks the glycolytic pathway downstream, preventing the generation of ATP from glucose metabolism. **Clinical Manifestations:** - During muscle contraction, ATP demand is high - Without functional glycolysis, muscles cannot generate sufficient ATP - This leads to energy crisis, muscle damage (rhabdomyolysis), and myoglobinuria - Symptoms are exercise-induced because resting muscles can rely on other fuel sources **Key Point:** PFK deficiency is also known as Tarui disease (Glycogen Storage Disease Type VII) and presents with exercise intolerance, muscle pain, and myoglobinuria. **High-Yield:** The block occurs at the committed step of glycolysis, preventing formation of the triose phosphates and subsequent ATP generation.