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

The purpose of the study was to examine the roles of active pyruvate dehydr ogenase (PDHa), glycogen phosphorylase (Phos), and their regulators in lact ate (Lac(-)) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO3 [metabolic alkalosis (ALK)] or CaCO3 [control (CON)]. Subjects (n = 8) were studied at rest, rest postingestion, and during cons tant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O-2 uptake ((V) over dot (O2max)). Radial artery and femoral venous blood samp les,leg blood flow; and biopsies of the vastus lateralis were obtained duri ng each power output. ALK resulted in significantly (P < 0.05) higher intra muscular Lac(-) concentration ([Lac(-)]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac(-)] (ALK 8.7 vs. CON 7.0 mmol/l), and leg La c(-) efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% (V) over dot (O2max). Th e increased intramuscular [Lac(-)] resulted from increased pyruvate product ion due to stimulation of glycogenolysis at the level of Phos a and phospho fructokinase due to allosteric regulation mediated by increased free ADP (A DP(f)), free AMP (AMP(f)), and free P-i concentrations. PDHa increased with ALK at 60% (V) over dot (O2max) but was similar to CON at 75% (V) over dot (O2max). The increased PDHa may have resulted from alterations in the acet yl-CoA, ADP(f), pyruvate, NADH, and H+ concentrations leading to a lower re lative activity of PDH kinase, whereas the similar values at 75% (V) over d ot (O2max) may have reflected maximal activation. The results demonstrate t hat imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidat ion resulting in an increase in Lac(-) production.