Regulation of fructose diphosphate aldolase concentrations in skeletal muscles of normal and dystrophic chickens.

We are using the glycolytic enzyme aldolase as a marker to investigate the molecular basis for reduced levels of specific enzyme activities associated with muscular dystrophy. Inbred strains of normal and dystrophic chickens were used as models to study the disease. In the present paper we show that: 1) aldolase & was the only isoenzyme present in normal and dystrophic muscles derived from lto 12-week-old birds; 2) aldolase & isolated from normal and dystrophic breast (“fast-twitch”) muscles were identical molecules on the basis of their electrophoretic, immunological, and catalytic properties; 3) the steady state level of aldolase activity in dystrophic breast muscle was only 40 to 50% of normal; 4) the reduced level of enzyme activity was associated with a corresponding reduction in the level of catalytically active aldolase molecules as determined in immunotitration experiments; 5) the reduced steady state level of aldolase molecules was associated with a corresponding reduction in the relative rate of synthesis of the enzyme in dystrophic breast muscle fibers as determined by short term isotope incorporation experiments conducted in viva and with muscle explants in culture; 6) large increases in synthesis of collagen or other non-muscle proteins by dystrophic muscle samples were not detected by electrophoretic and fluorographic analysis of the radioactive proteins synthesized by muscle slices in culture; 7) in contrast to the situation with “fast-twitch” (breast) muscle, aldolase content and relative rate of synthesis in mature lateral abductor (“slow-twitch”) muscles of dystrophic chickens were found to be essentially normal. We suggest that one of the manifestations of avian muscular dystrophy is a failure of fast-twitch muscle fibers to accurately perform the transition from one enzyme synthetic program to another which normally occurs around the time of hatching.