alpha-L-fucosidase in human fibroblasts. I. The enzyme activity polymorphism.

Low plasma alpha-L-fucosidase activity is a recessive polymorphic trait observed in 8% of the normal population. The molecular basis of this polymorphism remains unclear and its expression is tissue specific. As the low-activity (variant) phenotype is expressed in vitro in cultured human fibroblasts, this cell type was chosen to study the enzyme activity polymorphism. Fibroblast cell lines derived from individuals with low plasma fucosidase activity (variants) have less than 30% of the fucosidase activity of fibroblast cell lines established from individuals with high plasma fucosidase activity (nonvariants). No qualitative differences in the synthesis, processing, and extracellular release of newly made alpha-L-fucosidase could be demonstrated among variant and nonvariant cell strains. Cells pulsed with 3H-leucine for 10 min produce a 51-kDa protein which is rapidly processed to a 55-kDa intermediate. The latter is converted to a mature 59-kDa intracellular and a 61-kDa extracellular end product, in both variant and nonvariant fibroblast cell lines. Variant and nonvariant fibroblast cell lines also release relatively equal amounts of fucosidase into the extracellular medium. Therefore, differences in processing or extracellular release of fucosidase between variants and nonvariants are not the basic mechanism of this tissue-specific activity polymorphism.