Methylation of erythrocyte membrane phospholipids in patients with myotonic and Duchenne muscular dystrophy

Recent studies of rat erythrocyte membranes demonstrated that the transfer of methyl groups to phosphatidylethanolamine significantly altered membrane structure and function. Because membrane alterations were reported in red blood cells from patients with myotonic musclar dystrophy and Duchenne muscular dystrophy, we investigated these reactions as a potential explanation for the membrane defects of these disorders. Human erythrocyte membranes were found to catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine to form successively N-monomethylphosphatidylethanolamine (PMME), N,N-dimethylphosphatidylethanolamine (PDME), and phosphatidylcholine (PC). The half-maximal rate of [³H]methyl incorporation into PMME and PDME occurred at lower concentrations of SAM (3 and 11 μM, respectively) than that (46μM) needed for the incorporation into PC. Phospholipid methyltransferase activities in erythrocyte membranes increased with the age of the subject. Five of seven female patients with myotonic muscular dystrophy possessed elevated rates of phospholipid methylation compared with their sex and age-matched controls. The formation of PC in the red blood cells of one female patient were enhanced over a wide range of SAM concentrations indicating an increased Vmax rather than an altered Km. In contrast, male patients with myotonic dystrophy or with Duchenne muscular dystrophy had similar activities relative to age and sex-matched controls. Because only female patients with myotonic muscular dystrophy demonstrated an alteration in phospholipid methylation, these reactions do not represent the primary metabolic defect in either dystrophic disorder. However, these results suggest that an increased conversion of PE to PC may influence the expression of the primary defect especially in older female patients.