In vivo ATP synthesis rates in single human muscles during high intensity exercise

Abstract

In vivo ATP synthesis rates were measured in the human medial gastrocnemius muscle during high intensity exercise using localized 31P‐magnetic resonance spectroscopy (31P‐MRS). Six‐second localized spectra were acquired during and following a 30 s maximal voluntary rate exercise using a magnetic resonance image‐guided spectral localization technique. During 30 s maximal voluntary rate exercise, ATPase fluxes were predominantly met by anaerobic ATP sources. Maximal in vivo glycogenolytic rates of 207 ± 48 mM ATP min−1 were obtained within 15 s, decreasing to 72 ± 34 mM ATP min−1 by the end of 30 s. In contrast, aerobic ATP synthesis rates achieved 85 ± 2 % of their maximal capacity within 9 s and did not change throughout the exercise. The ratio of peak glycolytic ATP synthesis rate to maximal oxidative ATP synthesis was 2.9 ± 0.9. The non‐Pi, non‐CO2 buffer capacity was calculated to be 27.0 ± 6.2 slykes (millimoles acid added per unit change in pH). At the cessation of exercise, Pi, phosphomonoesters and CO2 were predicted to account for 17.2 ± 1.5, 5.57 ± 0.97 and 2.24 ± 0.34 slykes of the total buffer capacity. Over the approximately linear range of intracellular pH recovery following the post‐exercise acidification, pHi recovered at a rate of 0.19 ± 0.03 pH units min−1. Proton transport capacity was determined to be 16.4 ± 4.1 mM (pH unit)−1 min−1 and corresponded to a maximal proton efflux rate of 15.3 ± 2.7 mM min−1. These data support the observation that glycogenolytic and glycolytic rates are elevated in vivo in the presence of elevated Pi levels. The data do not support the hypothesis that glycogenolysis follows Michealis‐Menten kinetics with an apparent Km for [Pi]in vivo. In vivo ‐measured ATP utilization rates and the initial dependence on PCr and glycolysis were similar to those previously reported in in situ studies involving short duration, high intensity exercise. This experimental approach presents a non‐invasive, quantitative measure of peak glycolytic rates in human skeletal muscle.

Combined in vivo and in silico investigations of activation of glycolysis in contracting skeletal muscle

“…Therefore, it was chosen to deduce pathway influx from our own experimental data. For conditions of constant ATP, it was assumed that the PME resonance represented the summed concentration of glucose-1-phosphate (G1P), G6P, and fructose-6-phosphate (F6P), which is in accordance with reports from other investigators (15,56). The PME dynamics were well described by a linear function (data not shown).…”

“…In mammalian cells, skeletal muscle has been a key experimental model to study the regulation of glycolysis and glycogenolysis. It can increase the glycogenolytic ATP production flux by two orders of magnitude during rest to work transitions on a timescale of seconds (56). This exceptionally broad and dynamic operational range of glyco(genol)ytic flux puts a high duty cycle upon the control mechanism(s) of this pathway.…”

Fiber Types in Mammalian Skeletal Muscles

“…Glycogen breakdown is activated by the increase of AMP and IMP concentrations which follows the start of contractile activity. In mixed human muscles in vivo, the rate of glycogen breakdown is estimated to be 1.9 -3.4 mmol·kg dry wt Ϫ1 ·s Ϫ1 (expressed in glucosyl units) (142,143) with peaks of 7.5 mmol·kg dry wt Ϫ1 ·s Ϫ1 after short high-intensity exercise (845). In human muscles, a pronounced difference in glycogenolysis rate has been re- ported between slow and fast fibers during maximal contractions: 0.35 and 0.52 mM/s in type 1 and type 2 fibers, respectively (834), or 0.18 and 3.54 mmol·kg dry wt Ϫ1 ·s…”

Skeletal Muscle Fatigue: Cellular Mechanisms

“…Because the creatine kinase (PCr ϩ ADP 7 Cr ϩ ATP) and the adenylate kinase (2ADP 7 AMP ϩ ATP) reactions are close to equilibrium, the net consumption of ATP leads to relatively stereotyped changes in the concentrations of ATP, ADP, P i , phosphocreatine (PCr), creatine (Cr), and AMP which can be calculated from the equilibrium constants (10,85 (30,117,168,286,406,455). However, virtually all of these measurements were made in whole muscle or muscle homogenates and hence reflect the spatially averaged change across all fibers present.…”