Disruption of the purine nucleotide cycle. A potential explanation for muscle dysfunction in myoadenylate deaminase deficiency.
A patient with symptoms of easy fatigability, postexercise myalgias, and delayed recovery of muscle strength after activity is described. Skeletal muscle from this patient had <1.0% normal myoadenylate deaminase activity and NH(3) was not released from muscle after ischemic exercise. In association with this enzyme deficiency, exercise led to a >90% reduction in muscle content of adenine nucleotides. No inosine monophosphate accumulated after exercise and total purine content of the muscle fell to 21% of control. Repletion of the adenine nucleotide pool in this patient was delayed compared to controls, and ATP content had only returned to 68% of control at 165 min after exercise. These studies demonstrate that disruption of the purine nucleotide cycle as a consequence of myoadenylate deaminase deficiency results in marked alterations in ATP content of muscle, and potentially, these changes in ATP content could account for muscle dysfunction in this patient.
D000659:AMP Deaminase / Q000172:deficiency*; D000227:Adenine Nucleotides / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D009709:Nucleotide Deaminases / Q000172:deficiency*; D005082:Physical Exertion; D011685:Purine Nucleotides / Q000378:metabolism*
D000227:Adenine Nucleotides; D011685:Purine Nucleotides; D009709:Nucleotide Deaminases; D000659:AMP Deaminase