Decreased structure-linked latency of lysosomal dipeptidyl aminopeptidase-I activity in Duchenne muscular dystrophy fibroblasts.
Crude lysosomal pellets were prepared from skin fibroblasts grown from patients having Duchenne muscular dystrophy, and from normal controls. Disruption of the lysosomes by nonionic detergents resulted in the expression of latent activity of the enzyme dipeptidyl aminopeptidase-I(DAP-I). Duchenne lysosomes showed less structure-linked latency than those from normal controls, and sedimentation studies demonstrated that the difference was not caused by increased leakage of the enzyme from lysosomes. Permeability properties of the lysosomes for an artificial substrate revealed no difference of the apparent Km. However, in intact lysosomes the apparent K, for Cl- of this chloride-requiring enzyme was found to be lower in DMD lysosomes. The apparent increase in entry for Cl- was closely related with the decreased amount of the DAP-I latency. High concentrations of extra-lysosomal Cl- corrected the abnormality.
D002403:Cathepsins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D004123:Dimethylamines / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D009136:Muscular Dystrophies / Q000201:enzymology*; D013696:Temperature
D002712:Chlorides; D004123:Dimethylamines; C014518:dodecyldimethylamine oxide; D002403:Cathepsins