Abnormal high-energy phosphate metabolism in human muscle phosphofructokinase deficiency

We studied the pattern of high-energy phosphate metabolism in five patients with phosphofructokinase deficiency (PFKD) and five healthy subjects (HS) during graded rhythmic handgrip performed for 5 min at 17, 33, 50, and 100% of maximal voluntary contraction (MVC). The range of MVC was similar in both groups. Force production was recorded, and intracellular concentrations of phosphorus compounds and pH were measured in the flexor digitorum profundus of the active forearm. At exercise intensities ≥50% MVC, changes in concentrations of high-energy phosphate metabolites were abnormal in PFKD. During maximal effort, [ADP], calculated from the creatine kinase reaction, was 64.3 ± 13.5 (SE) μmol/kg in PFKD vs. 25.7 ± 4.0 in HS (P < 0.05). Ammonia (NH₃), a product of AMP deamination and an index of muscle [AMP], increased approximately twofold more in venous effluent during maximal forearm exercise in PFKD than in HS (P < 0.05). Phosphocreatine concentration was 9.4 ± 1.3 (SE) mmol/kg in HS and 13.0 ± 1.7 in PFKD (P < 0.05). Inorganic phosphate concentration was 15.8 ± 1.4 mmol/kg in HS and 7.4 ± 0.5 in PFKD (P < 0.05). During strenuous exercise, PFKD patients exhibit an impairment in the rephosphorylation of ADP related to a subnormal oxidative capacity, an absence of glycolysis, and an attenuated breakdown of phosphocreatine.