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Mitochondria isolated from the hind leg muscle of normal and dystrophic mice (strain 129) were compared in their capacity to oxidize acetyl-1-14C-l-carnitine. Oxidation in the mitochondria from dystrophic animals was reduced by 80%. Carnitine acetyltransferase (EC 2.3.1.7) activity in the mitochondria was determined and showed a 35% reduction in the mitochondria from dystrophic muscle. A larger decrease (55%) was observed in the mitochondrial content of acid-soluble CoA. Although the combined decreases in carnitine acetyltransferase and CoA can largely account for the observed decrease in acetylcarnitine oxidation in the mitochondria isolated from dystrophic muscle, it is conceivable that some defect may still exist in the utilization of acetyl groups in the tricarboxylic acid cycle.

Cofactor requirements for the oxidation of palmitate-1-14C by 600 × g supernatant fraction of mouse skeletal muscle homogenate and by skeletal muscle mitochondria are described. Optimal oxidation of palmitate-1-14C by skeletal muscle mitochondria requires the presence of carnitine, ATP, CoA, and a Krebs cycle intermediate (e.g. succinate). Succinate, malate, alpha-ketoglutarate, and oxaloacetate are all equally effective in supporting the oxidation, but isocitrate is less effective. The oxidation of palmitate-1-14C by 600 × g supernatant fraction of muscle homogenate as well as by skeletal muscle mitochondria from dystrophic mice is significantly decreased compared with that of the normal littermate controls. The present results, together with the previous findings, suggest that the decrease in oxidation of palmitate-1-14C by the dystrophic muscle preparations is most likely due to a defect in one or more of the steps of the Krebs cycle.

Adenyl cyclase and cyclic nucleotide phosphodiesterase activities were assayed in homogenates of hind leg skeletal muscle from dystrophic and normal mice. Adenyl cyclase activity was stimulated 2.5 times by epinephrine and 6 times by fluoride over the basal activity in both dystrophic and normal mice. The activity of adenyl cyclase from dystrophic muscle of mice was significantly higher than that of normal mice under all the conditions tested (i.e. basal, epinephrine and fluoride). Cyclic nucleotide phosphodiesterase from skeletal muscle of mice has two K(m)’s (2.1 and 11 μmol/1) which suggests the existence of either two forms of enzyme or a single enzyme with negative cooperativity. The activity of this enzyme was significantly elevated in the skeletal muscle of dystrophic mice compared to the normal controls. The available evidence suggests that the same cyclic nucleotide phosphodiesterase is responsible for the hydrolysis of both cyclic AMP and cyclic GMP.

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