Introduction
AMP deaminase (AMPd) catalyses deamination of AMP to IMP. Due to a common hereditary mutation in the AMPD1 gene encoding the muscle specific isoform of AMP deaminase, ˜2% of Caucasians are homozygous for the mutation (-/-) and therefore have extremely low levels of AMPd, ˜20% are heterozygous (+/-) and have intermediate levels and ˜78% are homozygous normal (+/+) and have high levels of AMPd in their skeletal muscle Norman et al. (1998). The aim of the study was to investigate the acute metabolic response during sprint exercise in subjects with different levels of AMPd attributable to their AMPD1 genotype.
Methods
Eighteen healthy subjects were chosen from a large population sample that had been previously analysed for AMPD1 genotypes by PCR amplification and restriction endonuclease analysis. 7 subjects were +/+, 7 were +/- and 4 were -/-. Subjects performed a 30-s maximal sprint on a cycle ergometer. Biopsies were obtained from vastus lateralis at rest and immediately after exercise and analysed for IMP and lactate. Venous blood samples were taken 3, 6 and 9 min after exercise and analysed for ammonia and lactate. The study was approved by the Ethics Committee of the Karolinska Institute.
Results
Sprint exercise increased the muscle IMP content by 9±3, 6±2 and 0.2±0.4 mmol/kg dry weight in +/+, +/- and -/- genotypes, respectively (ANOVA, p<0.0001). The IMP accumulation was significantly lower in -/- than in +/- or +/+ and also significantly lower in +/- when compared to +/+. In agreement with the IMP accumulation, the -/- did not accumulate ammonia in plasma to any notable extent after exercise. In contrast, the plasma ammonia accumulation was higher in +/- than in +/+ after 3, 6, and 9 min post- exercise; 87±24, 120±28 and 95±21 vs 51±14, 71±30 and 70±30 µmol/l. Muscle lactate content immediately after exercise was not statistically different between the genotypes. However, the time course for the accumulation of lactate in blood was different for the three genotypes (ANOVA, p=0.001). The peak value for lactate was detected at 9 min after exercise for the +/+, at 6 min for the +/- and at 3 min for the -/- and was 10±2, 12±2 and 10±3 mmol/l for the +/+, +/- and -/- genotypes, respectively.
Conclusions
The results indicate that the release of metabolites, from muscle to blood have a different time course for the three genotypes. This may be due to an enhanced blood flow response in subjects with decreased levels of AMPd. This proposal is based on the hypothesis that cytosolic 5'nucleotidase is more competitive for available AMP in these individuals leading to a higher production of skeletal muscle adenosine.
References
Norman B., Mahnke-Zizelman, D.K., Vallis A. & Sabina, R.L. 1998. J Appl Physiol 85, 1273-1278.