. . . . "Normal human fibroblasts and fibroblasts from a patient with \u03B1-mannosidosis were grown in the presence or absence of 100 \u03BCM swainsonine for 7 days. Accumulated oligosaccharides were isolated and analysed by high performance liquid chromatography (HPLC) and methylation analysis. Man\u03B11\u21923Man\u03B21\u21924GlcNAc and Man\u03B11\u21922Man\u03B11\u21923Man\u03B21\u21924GlcNAc (where Man is D-mannose and GlcNAc is N-acetyl-D-glucosamine) comprised >80% of the total oligosaccharides in untreated mannosidosis cells. However, Man\u03B11\u21926[Man\u03B11\u21923]Man\u03B21\u21924GlcNAc was the major Man3 GlcNAc isomer present after 7 days of swainsonine treatment. No mannose-containing oligosaccharides were detected in control fibroblasts in the absence of swainsonine but, in its presence, oligosaccharides containing 2-9 mannose residues accumulated. Man\u03B11\u21926[Man\u03B11\u21923] Man\u03B11\u21926[Man\u03B11\u21923]-Man\u03B21\u21924GlcNac and Man\u03B11\u21926-[Man\u03B11\u21923]Man\u03B21\u21924GlcNac were the major components (67%). Surprisingly, Man\u03B11\u21923Man\u03B21\u21924GlcNAc was only observed in swainsonine-treated control cells during the recovery period after removal of swainsonine. These studies suggest the presence of a second lysosomal \u03B1-mannosidase activity which is unaffected in genetic \u03B1-mannosidosis, but is inhibited by swainsonine. This enzyme would cleave the \u03B1(1\u21926)-linked mannose residue from branched Man3 GlcNAc to form Man\u03B11\u21923Man\u03B21\u03B24GlcNAc. To confirm this hypothesis, fractions from \u03B1-mannosidosis and control fibroblasts that bound to concanavalin A (ConA)-Sepharose and were eluted with 0.5 M \u03B1-methyl mannoside were incubated at pH 4.0 with Man\u03B11\u21926[Man\u03B11\u21923]Man\u03B21\u21924-GlcNac. As anticipated,Man\u03B1l\u21923Man\u03B21\u21924GlcNac was the sole product using enzyme from mannosidosis fibroblasts, while the major product from control fibroblasts was Man\u03B1l\u21926Man\u03B21-\u21924GlcNAc. This confirmed the presence of a swainsonine-inhibitable \u03B1(1\u21926)-mannosidase activity unaffected by the disease. The differing substrate specificities of the \u03B1(1\u21926)-mannosidase and the major lysosomal \u03B1-mannosidase indicate that the \u03B1(1\u21926)-mannosidase plays an important role in the generation of the oligosaccharides accumulated in \u03B1-mannosidosis patients." . . . . . . . . . "A human lysosomal \u03B1(1\u21926)-mannosidase active on the branched trimannosyl core of complex glycans" . . . . . . . . . . . "2.4.327" . .