Effect of induced metabolic acidosis on human skeletal muscle metabolism during exercise

Effect of induced metabolic acidosis on human skeletal muscle metabolism du ring exercise. The roles of pyruvate dehydrogenase (PDH), glycogen phosphor ylase (Phos), and their regulators in lactate(Lac(-)) metabolism were exami ned during incremental exercise after ingestion of 0.3 g/kg of either NH4Cl [metabolic acidosis (ACID)] or CaCO3 [control (CON)]. Subjects were studie d at rest, at rest postingestion, and during continuous steady-state cyclin g at three stages (15 min each): 30, 60, and 75% of maximal oxygen uptake. Radial artery and femoral venous blood samples, leg blood flow, and biopsie s of the vastus lateralis were obtained during each power output. ACID resu lted in significantly lower intramuscular concentration of [Lac(-)] (ACID 4 0.8 vs. CON 56.9 mmol/kg dry wt), arterial whole blood [Lac(-)] (ACID 4.7 v s. CON 6.5 mmol/l), and leg Lac(-) efflux (ACID 3.05 vs. CON 6.98 mmol 1(-1 ) min(-1)). The reduced intramuscular [Lac(-)] resulted from decreases in p yruvate production due to inhibition of glycogenolysis, at the level of Pho s alpha, and phosphofructokinase, together with an increase in the amount o f pyruvate oxidized relative to the total produced. The reduction in Phos a lpha activity was mediated through decreases in transformation, decreases i n free inorganic phosphate concentration, and decreases in the posttransfor mational allosteric regulator free AMP. Reduced PDH activity occurred with ACID and may have resulted from alterations in the concentrations of acetyl -CoA, free ADP, pyruvate, NADH, and H+, leading to greater relative activit y of the kinase. The results demonstrate that imposed metabolic acidosis in skeletal muscle results in decreased Lac(-) production due to inhibition o f glycogenolysis at the level of Phos and increased pyruvate oxidation at P DH.