Enhanced breakdown of arylsulfatase A in multiple sulfatase deficiency.
Multiple sulfatase deficiency (mucosulfatidosis) is a lysosomal storage disorder characterized by the decrease in activities of all known sulfatases. To measure the apparent rate of synthesis and the half-life of arylsulfatase A in multiple sulfatase deficiency, fibroblasts from patients with the disease and from controls were subjected to pulse-chase labelling with radioactive amino acids. Arylsulfatase A and cathepsin D, a lysosomal enzyme that is not affected in multiple sulfatase deficiency, were isolated from cells and media by immunoprecipitation. The labelled polypeptides were separated by polyacrylamide gel electrophoresis, visualized by fluorography and quantified by liquid scintillation counting. Using single and double isotope techniques it was found that, as compared to cathepsin D, the apparent rate of synthesis of arylsulfatase A was 2--5 times lower and the half-life 4--9-times shorter in multiple sulfatase deficiency than in control fibroblasts. In multiple sulfatase deficiency fibroblasts the rates of endocytosis and the stabilities of endocytosed arylsulfatases A isolated from human urine and bovine tests were equal to those in metachromatic leucodystrophy fibroblasts. We postulate that in normal cells a gene product exists that affects the stability of sulfatases and that multiple sulfatase deficiency is due to a mutation in this gene.
D000818:Animals; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002553:Cerebroside-Sulfatase / Q000096:biosynthesis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology; D006207:Half-Life; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D013429:Sulfatases / Q000172:deficiency* / Q000378:metabolism*
D013429:Sulfatases; D002553:Cerebroside-Sulfatase; D002403:Cathepsins; D002402:Cathepsin D