Biosynthesis, processing, and extracellular release of alpha-L-fucosidase in lymphoid cell lines of different genetic origins.

In humans, the quantity of alpha-L-fucosidase in serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. Lymphoid cell lines derived from individuals with either low, intermediate, or high alpha-L-fucosidase in serum were established. Steady-state levels of intracellular and extracellular alpha-L-fucosidase as well as rates of synthesis and secretion of enzyme overlapped among the cell lines. Thus, in vivo serum phenotypes were not expressed in this system. No appreciable differences in the qualitative processing of newly made alpha-L-fucosidase were observed among these lymphoid cell lines. Cells pulse-labeled with 35S-methionine from 0.25 to 2 hr had an intracellular form of enzyme with a Mr = 58,000. Cells pulsed for 1.5 hr and chased for 21 hr with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. All three enzyme forms were glycoproteins with a common polypeptide chain of Mr = 52,000 but with different carbohydrate moieties. No evidence for a high molecular mass precursor form of alpha-L-fucosidase was found. Fucosidosis is a rare, inherited disease in which alpha-L-fucosidase activity in tissues and body fluids is low or absent. The mutations for fucosidosis and the serum polymorphism map separately. Lymphoid cells from two siblings with fucosidosis had 8-fold to 341-fold less intracellular alpha-L-fucosidase protein with 11-fold to 56-fold lower specific activities than control cells. Residual mutant enzyme was a glycoprotein with a polypeptide chain virtually the same size (Mr = 52,000) as control enzyme. However, residual mutant enzyme was hypoglycosylated and hypersecreted as compared to control enzyme.