Lysosomal glycosidases

Most glycosidases work best around neutral pH, although such acid enzymes as lysosomal glycosidases may favor the range between pH 3.5 and 5, and pH optima may be as low as pH 2.2.70,71... 

Moreover, during the past few years, a glycoprotein pathology that is due to a lack of lysosomal glycosidases has been discovered, and the term glycoproteinosis has been coined. 

For instance, the liver Kupffer cells and macrophages probably have on their surfaces lectin-like components which recognize a manose determinant of lysosomal glycosidase (e.g. glycoprotein enzyme) and remove them from the blood circulation A similar effect which is applied in affinity chromatography... 

P. D. Stahl, J. S. Rodman, M. J. Miller, and P. H. Schlesinger. Evidence for receptor-mediated binding of glycoproteins and lysosomal glycosidases by alveolar macrophages. Proc. Natl Acad. Sci. USA 75 1399 (1978). 

If there is an inherited defect in SAP or a lysosomal glycosidase, GSL accumulates within the lysosome upstream of the defective reactions, resulting in progressive disease pathology. 

This is the reason why non-circulating human enzymes appeared us as better candidates for prodrug activation in the ADEPT approach. We selected in our work the human lysosomal glycosidases a-D-galactosidase and p-D-glucuronidase. An additional argument for the choice of these enzymes is that they can be used in conjunction with highly hydrophilic... 

Deficiencies of lysosomal glycosidases cause partially degraded carbohydrates from proteoglycans, glycoproteins, and glycolipids to accumulate within membrane-enclosed vesicles inside cells. These residual bodies can cause marked enlargement of the organ with impairment of its function. 

These findings have been substantiated by the observation that the selective hepatic uptake of the lysosomal glycosidase 3-D-2-acetamido-2-deoxyhexosidase, which is a glycoprotein with terminal D-mannosyl residues, is by the sinusoidal cells. ... 

Our own interest arose from the realization that ascorbic acid, known to be required for collagen synthesis, might be required in increased amounts for the protective encapsulation of tumors (253) and from the independent simultaneous conclusion that the ascorbate molecule (or some residue thereof) must be involved in the feedback inhibition of lysosomal glycosidases (60) responsible for malignant invasiveness (48). From these joint beginnings came the realization that ascorbic acid could be implicated in many other aspects of host resistance and even the tentative proposal that host resistance, no matter how measured, is ultimately dependent upon the availability of ascorbic acid. 

To summarize, the dangerous features of neoplastic cell behavior (invasiveness, selective nutrition, and perhaps growth) are caused by microenvironmental depolymerization. In turn, this matrix destabilization is brought about by constant exposure to lysosomal glycosidases continually released by the neoplastic cells. Finally, ascorbate is involved in the natural restraint of this degradative enzymic activity. 

Fisher, K. J., and N. N. Aronson, Jr., Cloning and expression of the cDNA sequence encoding the lysosomal glycosidase di-N-acetylchitobiase, J Biol Chem, 1992, 267, 19M7-196I6. 

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