Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo.

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.

Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (type 1) diabetes.

This study asked whether the energetic properties of muscles are changed by insulin-dependent diabetes mellitus (or type 1 diabetes), as occurs in obesity and type 2 diabetes. We used (31)P magnetic resonance spectroscopy to measure glycolytic flux, oxidative flux, and contractile cost in the ankle dorsiflexor muscles of 10 men with well-managed type 1 diabetes and 10 age- and activity-matched control subjects. Each subject performed sustained isometric muscle contractions lasting 30 and 120 s while attempting to maintain 70-75% of maximal voluntary contraction force. An altered glycolytic flux in type 1 diabetic subjects relative to control subjects was apparent from significant differences in pH in muscle at rest and at the end of the 120-s bout. Glycolytic flux during exercise began earlier and reached a higher peak rate in diabetic patients than in control subjects. A reduced oxidative capacity in the diabetic patients' muscles was evident from a significantly slower phosphocreatine recovery from a 30-s exercise bout. Our findings represent the first characterization of the energetic properties of muscle from type 1 diabetic patients. The observed changes in glycolytic and oxidative fluxes suggest a diabetes-induced shift in the metabolic profile of muscle, consistent with studies of obesity and type 2 diabetes that point to common muscle adaptations in these diseases.

A "functional biopsy" of muscle properties in sprinters and distance runners.

PURPOSE: Fast- and slow-twitch human muscle fibers exhibit large (two- to threefold) differences in metabolic enzyme activities and contractile economy. We asked whether comparable flux differences are evident in the muscles of athletes specializing in extremely different (i.e., sprint and long-distance) running events. METHODS: We took an in vivo "functional biopsy" of the ankle dorsiflexor muscles of 17 members of a university track team by using (31)P magnetic resonance spectroscopy. Ten sprinters (SPR) and seven distance runners (DIS) performed rapid isometric dorsiflexions against the resistance of a plastic foot holder. The contractile cost of exercise and glycolytic flux were calculated from changes in pH, [PCr], and [P(i)] during ischemic exercise, and oxidative capacity was calculated from PCr recovery kinetics after aerobic exercise. RESULTS: Contractile costs were 47% higher in SPR than in DIS, whereas oxidative capacities were 52% higher in DIS than in SPR. Surprisingly, glycolytic ATP production was similar in the two groups. CONCLUSION: The muscles of SPR and DIS exhibit clear differences in energetic properties, but these differences are smaller than the two- to three-fold variations seen in the properties of individual muscle fibers.

Fiber recruitment affects oxidative recovery measurements of human muscle in vivo.

PURPOSE: Fast-twitch and slow-twitch muscle fibers are known to have distinct metabolic properties. However, it has not been clearly established whether such heterogeneity within mixed-fiber muscles can influence measurements of energy metabolism in vivo. We therefore tested the hypothesis that differences in muscle fiber recruitment can cause differences in whole-muscle oxidative recovery from exercise. METHODS: We used (31)P magnetic resonance spectroscopy to measure oxidative ATP synthesis in the ankle dorsiflexor muscles of eight healthy volunteers under a variety of recruitment conditions. Oxidative ATP synthesis after isometric exercise was quantified as the rate constant k(PCr), the reciprocal of the time constant of PCr recovery. RESULTS: k(PCr) was 37% higher after low-force ramp contractions (which primarily recruit slow-twitch fibers) than after ballistic contractions to the same peak force (which recruit both fast- and slow-twitch fibers). k(PCr) was also 24% higher after low-force ramp contractions than after high-force ramp contractions, presumably reflecting the recruitment of fast-twitch fibers at high forces. CONCLUSION: Our results indicate that the muscle fibers recruited first in voluntary contractions have a higher oxidative capacity than those recruited last. Such metabolic differences among fibers can confound whole-muscle measurements and thus need to be taken into account when studying voluntary exercise.