Synthesis and maturation of cross-reactive glycoprotein in fibroblasts deficient in arylsulfatase A activity.

The biosynthesis of arylsulfatase A was studied in cultured fibroblasts by pulse-chase labeling with [2-3H]mannose; the enzyme was isolated by immunoprecipitation and denaturing polyacrylamide gel electrophoresis. In normal fibroblasts, and in fibroblasts from a patient with multiple sulfatase deficiency, the enzyme was synthesized as a glycoprotein of apparent molecular weight of 59,000; half of it was processed over a period of 4 days to Mr = 57,000. The precursor chain of Mr = 59,000 was secreted in the presence of 10 mM NH4Cl. An immunoprecipitable glycoprotein of normal size was synthesized by fibroblasts from two unrelated patients with metachromatic leukodystrophy, but this material disappeared within twenty hours. In fibroblasts from an individual with pseudo-deficiency of arylsulfatase A, the immunoprecipitable precursor glycoprotein was smaller (Mr = 56,000). The synthesis of cross-reactive proteins with altered properties supports the concept of allelic mutations as the genetic basis of metachromatic leukodystrophy and of arylsulfatase A pseudo-deficiency.