Muscle metabolism during lactate infusion in human phosphofructokinase deficiency

We studied the effect of intravenous infusion of sodium lactate (La) on muscle high-energy phosphate metabolism, pH, and venous effluent [NH3] in three patients with muscle phosphofructokinase (PFK) deficiency and three healthy subjects during maximal-effort rhythmic handgrip exercise (5 s of contraction alternated with 5 s of rest) performed for 3 min. Healthy subjects were matched to PFK-deficient patients for gender and maximal handgrip strength. Force production was recorded and during lactate infusion was matched to that without lactate. 31P-magnetic resonance spectroscopy was used to measure intracellular phosphocreatine (PCr), orthophosphate (Pi), ATP, and pH in the flexor digitorum profundus of the exercising forearm. La infusion had no effect on healthy subjects or patients during rest. In healthy subjects, La infusion had no effect on depletion of PCr; accumulation of Pi, ADP, or venous effluent NH3; or decline in pH in exercising muscle. In contrast, during exercise in PFK-deficient patients, [PCr] was higher (17.9 +/- 1.9 vs. 13.1 +/- 1.4 mmol/kg) and [phosphomonoester] (11.4 +/- 1.3 vs. 6.5 +/- 1.4 mmol/kg), [Pi] (9.2 +/- 1.8 vs. 5.0 +/- 0.7 mmol/kg), [ADP] (60.4 +/- 7.0 vs. 37.9 +/- 9.9 mumol/kg), and venous effluent [NH3] (335 +/- 136 vs. 176 +/- 61 mM) were lower (P < 0.05) during La infusion than in control conditions. The effects of La infusion on intracellular [PCr], [Pi], [phosphomonoester], [ADP], and [NH3] in PFK-deficient patients are consistent with the hypothesis that exogenous La augments the rate of oxidative phosphorylation in active muscle by bypassing the enzymatic block at PFK.