Increased phosphofructokinase protein expression in patients with myophosphorylase deficiency (McArdle’s disease).

McArdle’s disease is an autosomal recessive condition resulting in the absence of skeletal muscle phosphorylase. This condition places skeletal muscle under metabolic stress as evidenced by elevated creatine kinase activity in blood and muscle pain and cramping during mild to moderate exercise. We hypothesized that cellular adaptations would occur to compensate for the reduced glycogen flux including; enhanced glucose uptake/glycolytic flux and increased mitochondrial capacity. Muscle biopsies were obtained from patients with McArdle’s disease (N=11) and age and sex matched patient control subjects (N=13). Western blotting was used to determine protein content for: phosphofructokinase (PFK), AMP activated protein kinase (AMPK), citrate synthase (CS) and cytochrome oxidase (COX subunits II and IV). PFK protein content was higher in McArdle’s patients as compared to controls (P < 0.05), with no differences in total AMPK, CS, COX II or COX IV (P = NS). In summary, it appears that an increased glycolytic flux capacity (PFK) is an important compensatory strategy by skeletal muscle in response to a reduction in glycogenolytic flux; whereas, mitochondrial biogenesis does not appear to be altered significantly. These results support the observations of clinical improvement with exogenous glucose provision during exercise in McArdle’s patients by enhancing pyruvate availability via glycolysis ( N Engl J Med 2003; 349 :–2509). (This work was supported with a donation from Giant Tiger Stores).