Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans
Article first published online: 5 AUG 2004
The Journal of Physiology
Volume 533, Issue 3, pages 881–889, June 2001
How to Cite
Tarnopolsky, M. A., Parise, G., Gibala, M. J., Graham, T. E. and Rush, J. W. E. (2001), Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans. The Journal of Physiology, 533: 881–889. doi: 10.1111/j.1469-7793.2001.t01-1-00881.x
- Issue published online: 5 AUG 2004
- Article first published online: 5 AUG 2004
- (Received 22 December 2000; accepted after revision 3 February 2001)
- 1Myoadenylate deaminase (AMPD) deficiency is present in 1-2 % of the population. In theory, this deficiency may alter exercise energy metabolism by impairing the purine nucleotide cycle (PNC) and reducing tricarboxylic acid (TCA) cycle anaplerosis. The role of the PNC in TCA cycle anaplerosis is still a debated issue in physiology. Using patients with the AMPD1 mutation will allow a human ‘knockout’ approach to answering this question.
- 2Muscle AMPD activity and genotype (whole blood AMPD1 analysis) was used to classify participants into three groups: n= 3 with absence of AMPD activity and -/- AMPD1 genotype (homozygous); n= 4 with less than 50 % normal AMPD activity and +/- genotype (heterozygous) and n= 12 with normal AMPD activity and +/+ genotype (control). Biopsies were taken from the vastus lateralis muscle before and after incremental cycle ergometry exercise to exhaustion. The muscle biopsies were analysed for AMPD activity, purine nucleotides/nucleosides and bases, creatine, phosphocreatine, amino acids, and the TCA cycle intermediates malate, citrate and fumarate.
- 3Time to exhaustion on the cycle ergometer was not different between groups. Muscle adenosine monophosphate increased significantly with exercise for homozygous subjects as compared with the other groups (P < 0.05). Inosine monophosphate increased significantly after exercise for control (P < 0.05) but not for the homozygous subjects. There were no other between-group differences for any other measured variables.
- 4In summary, complete and partial muscle AMPD deficiency did not affect TCA cycle anaplerosis, phosphocreatine hydrolysis, energy charge or exercise performance.