Acidosis inhibits oxidative phosphorylation in contracting human skeletal musclein vivo

Abstract

This study tested the hypothesis that acidic pH inhibits oxidative ATP supply during exercise in hand (first dorsal interosseus, FDI) and lower limb (leg anterior compartment, LEG) muscles. We measured oxidative flux and estimated mitochondrial capacity using the changes in creatine phosphate concentration ([PCr]) and pH as detected by 31P magnetic resonance (MR) spectroscopy during isometric exercise and recovery. The highest oxidative ATP flux in sustained exercise was about half the estimated mitochondrial capacity in the LEG (0.38 ± 0.06 vs. 0.90 ± 0.14 mm ATP s−1, respectively), but at the estimated capacity in the FDI (0.61 ± 0.05 vs. 0.61 ± 0.09 mm ATP s−1, respectively). During sustained exercise at a higher contraction rate, intracellular acidosis (pH < 6.88) prevented a rise in oxidative flux in the LEG and FDI despite significantly increased [ADP]. We tested whether oxidative flux could increase above that achieved in sustained exercise by raising [ADP] (> 0.24 mm) and avoiding acidosis using burst exercise. This exercise raised oxidative flux (0.69 ± 0.05 mm ATP s−1) to nearly twice that found with sustained exercise in the LEG and matched (0.65 ± 0.11 mm ATP s−1) the near maximal flux seen during sustained exercise in the FDI. Thus both muscles reached their highest oxidative fluxes in the absence of acidosis. These results show that acidosis inhibits oxidative phosphorylation in vivo and can limit ATP supply in exercising muscle to below the mitochondrial capacity.

Contribution of Intramuscular Oxidative Metabolism to Total ATP Production during Forearm Isometric Exercise at Varying Intensities

“…Intracellular pH level at 70%MVC was 6.93 ± 0.01 (ranging from 6.80 to 7.03). This is the upper level of intracellular acidosis (pH = 6.8) on oxidative phosphorylation as shown in previous studies (Conley et al 2001;Jubrias et al 2003). This result suggests that the effect of intracellular acidosis at 70%MVC was greater than at a lower %MVC.…”

“…This result suggests that the effect of intracellular acidosis at 70%MVC was greater than at a lower %MVC. However, previous studies reported that relatively mild acidosis (pH 6.8-6.9) prevented a rise in oxidative flux despite a substantial rise in ADP (Jubrias et al 2003). Thus, this mild acidosis at 70%MVC might also attenuate the availability of intramuscular O 2 in muscle.…”

Skeletal muscle energetics with PNMR: personal views and historic perspectives

“…Secondly, many enzyme activities related to ATPase and glycolysis are affected by the pH. However, mitochondrial enzymes are not affected (89), although recent works came to a different conclusion in studies of human (90) and cat (91) muscles. Reducing ADP by low pH [eqn (1)] actually suppresses the mitochondrial respiration.…”

Building strength, endurance, and mobility using an astaxanthin formulation with functional training in elderly

“…The TA muscle is important in ankle dorsiflexion and represents a simple system connecting muscle mechanics and energetics to foot movement30 and is a critical part of walking mobility. The subject performed a maximal voluntary contraction (MVC) using ankle dorsiflexion for ~5 sec by pulling on a strap that secured the foot to a force transducer platform.…”