T.P.29: Role of AMP deaminase and adenylate kinase in production of ammonia in skeletal muscle of patients with McArdle’s disease

Abstract

McArdle’s disease is characterized by deficiency of enzyme myophosphorylase that disrupts the mechanism of glycogen breakdown in skeletal muscle. In McArdle patients, during physical activities, little or no lactate is released in the skeletal muscle but level of ammonia gets excessively increased. Production of ammonia is catalysed by AMP deaminase (AMPD) and Adenylate kinase (AK). We measured the activities of AMPD and AK in 11 molecular genetically confirmed McArdle patients and compared with the respective activities of 27 healthy controls. AMPD deficiency is commonly found to be associated with a stop mutation p.Q12X in AMPD1 gene. Therefore, all McArdle patients and controls were screened for this mutation. The p.Q12X stop mutation was identified heterozygote in 2 patients and 7 controls. The AMPD activities in patients and controls that did not harbour this mutation were significantly higher than in respective heterozygote patients and controls. However, there was no significant difference in the AMPD activities between patients and controls. The activities of AK were also not significantly different in patients and controls (p = 0.644). Present study shows that the high ammonia production in McArdle patients is not based on enzyme induction of AMPD and AK but derives from other mechanisms (such as increased enzyme catalytic reaction, stimulated by for instance a highly concentrated ADP, or from alternative pathways of the muscle (like the protein metabolism).