Residual mannosidase activity in human mannosidosis: characterization of the mutant enzyme.

The prenatal diagnosis of affected fetuses in two families at risk for mannosidosis gave us the opportunity to study the residual alpha-mannosidase activity. We found an altered acidic alpha-mannosidase characterized by lowered affinity toward the substrate, displacement of maximal activity toward pH 4-5, thermal lability, different migration in electrophoresis, and apparent change in molecular weight at alkaline pHs. The immunological properties seem unchanged since the enzyme was precipitated by an antiacidic alpha-mannosidase antiserum. The mutant enzyme instability, provoked by dialysis, and its reactivation after addition of dialysis fluid, suggests an association-dissociation phenomenon. We propose a possible hypothesis that a low molecular weight ligand is necessary to maintain the activity of the mutant enzyme.