X-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: Effects of oral allopurinol and adenylate

Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

“…Duchenne muscular dystrophy (DMD), the most common type of dystrophy in humans, presents with the most severe symptoms and is the most extensively studied type of muscular dystrophy [93]. In DMD patients, skeletal muscle [ATP] and total AdNs are severely reduced (by up to~50%) [98][99][100][101][102][103]. Interestingly, investigations into the reduced [ATP] have uncovered extreme mitochondrial myopathies in DMD, thus expanding our recognition of DMD as a metabolic myopathy [104,105].…”

“…For example, increases in purine excretion in the urine of DMD patients suggests increased AdN turnover (degradation) [106]. Also, treatments aimed at increasing intracellular [ATP] in DMD muscle, either by stimulating purine salvage (adenylosuccinic acid; ASA) or by inhibiting purine breakdown (allopurinol), lead to positive outcomes such as improved muscular strength [100,104] and reduced lipid deposits [107]. However, it is not clear to what extent the nucleotide pool is enzymatically degraded (Figure 1) or merely lost by diffusion out of the cell due to chronic damage/disruption of the sarcolemma.…”

Clinical Applications of Nuclear Magnetic Resonance Spectroscopy: A Review

“…For years investigators using conventional biochemical techniques (Vignos & Warner 1963, Stengel-Rutkowski & Barthelmai 1973, Thompson & Smith 1978 and even in vitro NMR methods (Glonek et al 1981) have considered that the concentrations of phosphocreatine and ATP in muscle are diminished in dystrophy. This information is important since if true, the possibility that the level of ATP may be increased by therapy (Thompson & Smith 1978) requires investigation.…”

“…This information is important since if true, the possibility that the level of ATP may be increased by therapy (Thompson & Smith 1978) requires investigation. However, in all these works, non-collagen protein was adopted as the reference base and this denominator fails to consider the fibroblasts, fat cells, mononuclear cells, etc., that are present in Duchenne but not normal muscle and that undoubtedly contribute non-collagenous protein without adding phosphocreatine or ATP in significant amounts.…”

Purine biosynthesis de novo in rat skeletal muscle

“…Work with primary rat muscle cell cultures supports the conclusion that skeletal muscle utilizes the 'de novo' pathway for purine nucleotide synthesis (Brosh et al, 1982;Zoref-Shani et al, 1982). Interest in the study of muscle purine metabolism has been stimulated by the suggestion that allopurinol, a xanthine oxidase inhibitor, improves patients with Duchenne muscular dystrophy (Thomson & Smith, 1978), and also by the report of a muscle adenylate deaminase deficiency associated with skeletal-muscle dysfunction (Fishbein et al, 1978). * To whom reprint requests should be addressed.…”