title: Defective expression of alpha-L-fucosidase by lymphoid cells of a fucosidosis patient.
abstract: Fucosidosis is an inherited lysosomal storage disease due to a deficiency of alpha-L-fucosidase activity. Exponentially growing lymphoid cell cultures from a fucosidosis patient (JH) had 16-fold lower extracellular alpha-L-fucosidase protein and 72-fold lower intracellular alpha-L-fucosidase protein with negligible catalytic activity as compared with the mean of 19 control cultures. The percentage of total alpha-L-fucosidase protein released extracellularly by JH cells was 71% as compared with 35% +/- 9% for control cells. During a 1.5 h pulse with 35S-methionine, alpha-L-fucosidase was synthesized by JH cells as an intracellular doublet with Mr of 58,000 and 56,000 and by control cells as an intracellular form with Mr = 58,000. During a subsequent 21 h chase with unlabeled methionine, JH alpha-L-fucosidase was entirely secreted. In contrast, only 25%-30% of control enzyme was secreted with the remainder retained intracellularly. Thus, JH lymphoid cells synthesized a reduced amount of alpha-L-fucosidase that was catalytically inefficient and was hypersecreted. Treatment of JH alpha-L-fucosidase with N-glycanase produced polypeptide chains with Mr of 52,000 and 54,000. Previously, treatment of control alpha-L-fucosidase with N-glycancase produced a single polypeptide chain with Mr of 52,000 (Biochem Genet 1988; 26: 401-20). The doublet polypeptide chains of alpha-L-fucosidase in JH cultures may represent expression of two distinct allelic forms of mutant alpha-L-fucosidase.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263.
authors.forename: R A
authors.initials: RA
authors.lastname: DiCioccio
authors.forename: B A
authors.initials: BA
authors.lastname: Gordon
mesh_terms: D001402:B-Lymphocytes / Q000201:enzymology*; D002455:Cell Division; D002460:Cell Line; D005347:Fibroblasts / Q000201:enzymology; D005645:Fucosidosis / Q000201:enzymology* / Q000235:genetics; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D011233:Precipitin Tests; D005644:alpha-L-Fucosidase / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism
chemical_list: D008715:Methionine; D006026:Glycoside Hydrolases; C020668:glycanase; D005644:alpha-L-Fucosidase