The metabolic differences in the skeletal muscle of patients with
Duchenne muscular dystrophy (DMD) and normal subjects (controls) were investigated using in-vitro high-resolution
proton NMR spectroscopy. In all, 56 metabolites were unambiguously identified in the
perchloric acid extract of muscle tissue using one- and two-dimensional NMR. The concentrations of glycolytic substrate
glucose (Glc; p < 0.05), gluconeogenic
amino acids such as
glutamine (Gln; p < 0.05) and
alanine (Ala; p < 0.05) and the glycolytic product
lactate (Lac; p < 0.05) were statistically significantly lower in DMD patients as compared to controls. A significant reduction in the concentrations of total
creatine (TCr; p < 0.05), glycerophosphoryl
choline + phosphoryl
choline +
carnitine (GPC/PC/Car; p < 0.05),
choline (Cho; p < 0.05) and
acetate (Ace; p < 0.05) was also observed in these patients. Decrease in the level of
glucose may be attributed to the reduction in the concentrations of gluconeogenic substrates or membrane abnormalities in degenerated muscle of DMD patients. Lower levels of
choline containing compounds indicate membrane abnormalities. Decrease in the concentration of
lactate in the muscle of DMD patients may be due to the reduction in anaerobic glycolytic activity or lower substrate concentration. The decrease in the concentration of
acetate may reflect reduced transport of
fatty acids into mitochondria due to decreased concentration of
carnitine in DMD patients. Kreb's cycle intermediate
alpha-ketoglutarate was observed only in the diseased muscle, which is suggestive of predominant oxidative metabolism for energy generation.