title: Abnormal expression of alpha-L-fucosidase in lymphoid cell lines of fucosidosis patients.
abstract: Fucosidosis is an autosomal recessive lysosomal storage disease due to a deficiency of alpha-L-fucosidase activity in tissues and body fluids. Exponentially growing lymphoid cell cultures from four fucosidosis patients had 2.7-fold to 15.6-fold less extracellular alpha-L-fucosidase protein and 28.8-fold to 144.0-fold less intracellular alpha-L-fucosidase protein with negligible catalytic activity, compared to the mean of 19 control cultures. The percentage of total alpha-L-fucosidase protein released extracellularly by cultures from the four patients was 64 to 85%, compared to 35 +/- 9% for control cultures. Intracellular and extracellular enzyme forms in fucosidosis and control cell lines were glycoproteins containing polypeptide chains of Mr = 52,000. During a 1.5-hr pulse-label with 35S-methionine, alpha-L-fucosidase was synthesized by control cells and two fucosidosis cell lines as an intracellular form with Mr = 58,000. During a subsequent 21-hr chase with unlabeled methionine, mutant enzyme was almost entirely processed to an extracellular form with Mr = 62,000. In contrast, only 25-30% of control enzyme was processed to an extracellular form (Mr = 62,000), with the remainder retained intracellularly (Mr = 60,000). In the other two fucosidosis cell lines, alpha-L-fucosidase was synthesized as an intracellular form with Mr = 56,000 that was processed to an extracellular form with Mr = 60,000. In summary, the fucosidosis mutation(s) affected the catalytic activity, quantity, and extracellular release of alpha-L-fucosidase as expressed by lymphoid cells.
authors: Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263.
authors: R A
authors: RA
authors: DiCioccio
authors: J K
authors: JK
authors: Darby
authors: P J
authors: PJ
authors: Willems
mesh_terms: D002460:Cell Line; D005260:Female; D005645:Fucosidosis / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D009154:Mutation; D011233:Precipitin Tests; D005644:alpha-L-Fucosidase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D005644:alpha-L-Fucosidase