Comparison of the residual acidic alpha-D-mannosidase in three cases of mannosidosis.
Residual acidic alpha-D-mannosidase, corresponding to 5-16% of the activity in controls, was present in cultured fibroblasts from three unrelated patients with mannosidosis. The residual activity in all three cases had a higher value of Km and a marked lower thermal stability than the normal enzyme and was activated rather than inhibited by Co2+. A higher proportion of alpha-mannosidase B, separable on DEAE-cellulose, was present in the residual activity than in the normal activity. Acidic alpha-D-mannosidase that binds and activity that does not bind to concanavalin A were present in normal cells but both were deficient in mannosidosis. The residual activity in all three patients failed to cross-react with antiserum raised against the normal enzyme and no enzymically inactive cross-reacting material was detected. These results suggest that the genetic defect in the three cases is a mutation in the structural gene for acidic alpha-D-mannosidase. However, it was not possible to distinguish the mutations in the enzyme in these three cases by the biochemical techniques employed. Differences between the mutant activity in these three patients and that in other cases provide further evidence for genetic heterogeneity in mannosidosis.
D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology*; D002845:Chromatography; D002848:Chromatography, DEAE-Cellulose; D003035:Cobalt / Q000494:pharmacology; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D008361:Mannosidases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015032:Zinc / Q000494:pharmacology; D043323:alpha-Mannosidase
D003035:Cobalt; D008361:Mannosidases; D043323:alpha-Mannosidase; D015032:Zinc; D008358:Mannose