Erythrocyte membrane enzyme abnormalities in two hereditary disorders of muscle.
Enzymatic properties of erythrocyte membranes in Duchenne muscular dystrophy (DMD) and malignant hyperthermia (MH), two genetically determined abnormalities of skeletal muscle, were examined. Acetylcholinesterase (AChE) and ATPase activities were chosen for investigation since alterations in these enzymes have been demonstrated in animal models of dystrophy. A significant decrease in Na+,K+-ATPase activity was noted in DMD patients and a number of possible DMD carriers, suggesting that this enzyme may provide a useful marker of the carrier state in carriers not exhibiting an elevation in plasma creatine phosphokinase activity. No abnormalities in AChE were demonstrable in any of our DMD patients, indicating that human dystrophy is biochemically distinct from certain animal models of dystrophy (e.g., dystrophic mice) where erythrocyte AChE is decreased. In contrast, evidence was found in two known MH carriers, who had normal erythrocyte ATPase activities, for the presence of an altered membrane AChE characterized by an increase in substrate affinity and a large decrease in maximal hydrolytic rate. While the exact relevance of this membrane defect, if any, to the pathogenesis of MH remains to be seen, the presence of this modified enzyme may serve to identify those individuals in a family where a positive history of MH exists who are at risk of developing a hyperthermic crisis during anesthesia.
D009597:4-Nitrophenylphosphatase / Q000097:blood; D000110:Acetylcholinesterase / Q000097:blood*; D000251:Adenosine Triphosphatases / Q000097:blood*; D002648:Child; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
D000110:Acetylcholinesterase; D009597:4-Nitrophenylphosphatase; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase