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Am J Physiol Endocrinol Metab 278: E316-E329, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 2, E316-E329, February 2000

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

M. G. Hollidge-Horvat, M. L. Parolin, D. Wong, N. L. Jones, and G. J. F. Heigenhauser

Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada L8N 3Z5

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDHa), glycogen phosphorylase (Phos), and their regulators in lactate (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 constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O2 uptake (VO2 max). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly (P < 0.05) higher intramuscular 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 Lac- efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% VO2 max. The increased intramuscular [Lac-] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADPf), free AMP (AMPf), and free Pi concentrations. PDHa increased with ALK at 60% VO2 max but was similar to CON at 75% VO2 max. The increased PDHa may have resulted from alterations in the acetyl-CoA, ADPf, pyruvate, NADH, and H+ concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% VO2 max may have reflected maximal activation. The results demonstrate that 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 oxidation resulting in an increase in Lac- production.

glycogen phosphorylase; pyruvate dehydrogenase; lactate metabolism


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