DYSTROPHIN-DEPENDENT EFFICIENCY OF METABOLIC PATHWAYS IN MOUSE SKELETAL-MUSCLES

Muscles from the mdx mouse (X-linked genetic disorder similar to Duche nne muscular dystrophy) lack dystrophin-associated transsarcolemmal pr oteins(1) and show reduced maintenance metabolic rates(2). Here, micro calorimetric comparisons of metabolic stimulation by exogenous substra tes in isolated muscles revealed substrate-selective limitation of che mical reaction rates through both glycolytic and TCA-cycle pathways, i dentical in slow- and fast-twitch mdx muscles. This systemic approach, as opposed to comparisons of single-enzyme activities, sheds new ligh t on the function of dystrophin and associated proteins. The in vivo e fficiency of metabolic pathways may depend on stabilization of enzyme complexes by dystrophin-associated elements of the cytoskeleton.