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Published on: July 14, 2017
Plasma alpha-D-mannosidase in mucolipidosis II and mucolipidosis III
Abstract:
There is a marked increase in the acidic alpha-D-mannosidase in the plasma of a patient with mucolipidosis II and of a patient with mucolipidosis III. A small proportion (3--4%) of this acidic alpha-D-mannosidase does not bind to concanavalin A-Sepharose, suggesting an alteration in the glycosylation and some of the enzyme in these disorders. A slight elevation in intermediate alpha-D-mannosidase was also demonstrated in these samples by using a differential assay for the acidic and intermediate alpha-D-mannosidase activities. A combination of chromatography on concanavalin A-Sepharose and Sephadex G-200 showed that intermediate alpha-D-mannosidase components I2 and I4, which account for approximately 80% of the intermediate activity in normal plasma, were also present in ML II and ML III plasma. The minor intermediate alpha-D-mannosidase components in normal plasma, I1 and I3 were either present in small amounts or not detected. These results suggest that a defect in intermediate alpha-D-mannosidase is unlikely to be the primary defect in these disorders.
Insights
Patients with mucolipidosis II and III show increased acidic alpha-D-mannosidase, with altered glycosylation. Analysis suggests a defect in intermediate alpha-D-mannosidase is not the primary cause of these lysosomal storage diseases.
Area of Science:
- Biochemistry
- Genetics
- Enzymology
Background:
- Mucolipidosis II (ML II) and Mucolipidosis III (ML III) are rare genetic disorders.
- These diseases involve defects in lysosomal enzyme targeting and function.
- Alpha-D-mannosidase is a key enzyme implicated in lysosomal metabolism.
Purpose of the Study:
- To investigate the characteristics of alpha-D-mannosidase in patients with ML II and ML III.
- To determine if alterations in alpha-D-mannosidase contribute to the pathogenesis of ML II and ML III.
- To differentiate between acidic and intermediate forms of alpha-D-mannosidase in patient plasma.
Main Methods:
- Plasma samples from patients with ML II and ML III were analyzed.
- Enzyme activity assays were performed for acidic and intermediate alpha-D-mannosidase.
- Chromatographic techniques, including concanavalin A-Sepharose and Sephadex G-200, were employed.
Main Results:
- A significant increase in acidic alpha-D-mannosidase was observed in ML II and ML III patients.
- A portion of the acidic enzyme showed altered glycosylation, indicated by reduced concanavalin A binding.
- Intermediate alpha-D-mannosidase levels were slightly elevated, with specific components (I2, I4) present, while minor components (I1, I3) were reduced or absent.
Conclusions:
- The findings indicate altered glycosylation of alpha-D-mannosidase in ML II and ML III.
- The presence of major intermediate alpha-D-mannosidase components suggests this enzyme form is not the primary defect.
- Further research is needed to fully elucidate the enzyme deficiencies underlying ML II and ML III.
