- Hellsten, E.A. Richter, B. Kiens and J. Bangsbo
The Journal of Physiology. 1999;520;909-920
- The present study examined the regulation of human skeletal muscle AMP deamination during intense exercise and quantified muscle accumulation and release of purines during and after intense exercise.
- Seven healthy males performed knee extensor exercise at 64·3 W (range: 50-70 W) to exhaustion (234 s; 191-259 s). In addition, on two separate days the subjects performed exercise at the same intensity for 30 s and SO% of exhaustion time (mean, 186 s; range, 153-207 s), respectively. Muscle biopsies were obtained from m.v. lateralis before and after each of the exercise bouts. For the exhaustive bout femoral arterio-venous concentration differences and blood flow were also determined.
- During the first 30 s of exercise there was no change in muscle adenosine triphosphate (ATP), inosine monophosphate (IMP) and ammonia (NH3), although estimated free ADP and AMP increased 5- and 45-fold, respectively, during this period. After 186 sand at exhaustion muscle ATP had decreased (P < 0·05) by 15 and 19%, respectively, muscle IMP was elevated (P < 0·05) from 0·20 to 3·65 and 5·67 mmol (kg dry weightf\ respectively, and muscle NH3 had increased (P < 0·05) from 0·47 to 2·55 and 2·33 mmol (kg d.w.f1 , respectively. The concentration of H+ did not change during the first 30 s of exercise, but increased (P < 0·05) to 245·9 nmoll-1 (pH 6·61) after 186 sand to 374·5 nmoll-1 (pH 6·43) at exhaustion.
- Muscle inosine and hypoxanthine did not change during exercise. In the first 10 min after exercise the muscle IMP concentration decreased (P < 0·05) by 2·96 mmol (kg d.w.f1 of which inosine and hypoxanthine formation could account for 30%. The total release of inosine and hypoxanthine during exercise and 90 min of recovery amounted to 1·07 mmol corresponding to 46% of the net ATP decrease during exercise or 9% of ATP at rest.
- The present data suggest that AMP deamination is inhibited during the initial phase of intense exercise, probably due to accumulation of orthophosphate, and that lowered pH is an important positive modulator of AMP deaminase in contracting human skeletal muscle in vivo. Furthermore, formation and release of purines occurs mainly after intense exercise and leads to a considerable loss of nucleotides.
During intense exercise the rate of ATP utilisation in skeletal muscle is higher than the rate of ATP regeneration, which leads to an accumulation of ADP and AMP. To avoid a large accumulation of AMP within the cell, AMP is deaminated to IMP and ammonia/ammonium (in this paper we will represent both as ‘NH3 ‘) via the enzyme AMP deaminase (Lowenstein, t990). The maximal activity of AMP deaminase is high in skeletal muscle and the accumulation of IMP and NH3 in human muscle after intense exercise may amount to t 0 mmol (kg d.w.f1 (Sahlin et al. 1978; Graham et al. 1990; Bangsbo et al. 1992a; Tullson et al. 1995). The mechanism underlying the regulation of AMP deamination in human skeletal muscle is, however, unclear.