Lysosomal a-D-mannosidase

Opheim, D. J., and O. Touster, Lysosomal a-D-mannosidase of rat liver. Purification and comparison with the golgi and cytosolic a-D-mannosidases, J. Biol Chem., 1978, 253, 1017-... 

In mouse liver and kidney and in rat liver, a-D-mannosidase activity appeared to be equally distributed between the two cytoplasmic-granule fractions. With mouse spleen and cancer tissue, a considerable proportion of the enzyme was found free in the cytoplasm. Rat spleen, on the other hand, lacked this cytoplasmic fraction. Inasmuch as the enzyme within the cytoplasmic granules was not fully active in a sucrose homogenate until the membranes had been disintegrated, a-D-mannosidase conforms to the definition of a lysosomal hydrolase. 

The theory has been advanced that there exists in the cell a particulate structure somewhat smaller than the mitochondrion, the lyso-some, that contains certain autolytic enzymes in a latent situation. The lysosome theory55,56 is very largely based upon measurements made in sucrose homogenates of rodent liver. Although the results for a-D-mannosidase in this tissue (see Table IV) are not incompatible with the theory, the results for other tissues do not always conform to it. In particular, the contrast between mouse and rat spleen argues against a universal single particle to which a-D-mannosidase is confined. Apart from the results quoted in Table IV, not much work has been done on the intracellular location of a-D-mannosidase. 

Investigation of the inhibitory effects on glycosidases has been carried out for the hydroxylated pyrrolidines [65] and piperidines [73]. Among the pyrrolidines prepared only the l,4-dideoxy-l,4-imino-L-allitol (23) (Scheme 7) and its C-5 isomer showed any remarkable effects. They inhibited lysosomal a-manno-sidase rather than the processing a-mannosida e I and II [65], and their specificity is in accord with the structural requirements of azafuranose analogues of mannose for inhibiting mammalian a-D-mannosidases [80]. 

The pronounced and diverse biological activity of (- )-swainsonine (162) stems from its potency as an inhibitor of a-mannosidases, and its consequent ability to alter the course of glycoprotein processing. Mannosidases partially or wholly characterized during, or detected in, recent inhibition studies with the alkaloid include a-D-mannosidases in the parasite Trypanosoma cruzi 145,146) and in various insects 147,148), a murine lysosomal a-mannosidase 149), and a-mannosidases 1 and II from Vigna umbellata (rice beans) 150). The alkaloid was used to differentiate... 

A search for lysosomal hydrolases and related enzymes has been made in haemolysates from human and rabbit red cells.Apart from acid phosphatases, significant activities were found only for a-D-mannosidase, neutral a-D-glucosidase and 3-D-2-acetamido-2-deoxyhexosidase. 

A search for lysosomal hydrolases and related enzymes has been made in haemolysates from human and rabbit red cells. Apart from acid phosphatases, significant activities were found only for a-D-mannosidase, neutral o-D-glucosidase, and -D-2-acetamido-2-deoxyhexosidase. a-D-Mannosidase activity per cell in human red blood cells was 200-times lower than in white cells. The optimal pH was 5.5-6.0. Electrophoresis on cellulose acetate showed three bands. Haemolysates from four patients with mannosidosis were not deficient in a-D-mannosidase. Curves of pH activity and electrophoretic patterns were similar to those of controls. From its biochemical and genetic properties, it is concluded that red cell a-D-mannosidase differs from the lysosomal acid a-D-mannosidase. 

JSf -line) Chinese hamsters Cricetulus griseus) a-D-Mannosidase was chiefly a particulate enzyme and its decrease in XA animals was evident in nuclear, lysosomal-mitochondrial, and mitochondrial-microsomal fractions. 

Several differences occur between the interactions of glycosaminoglycans with a particular lysosomal protein leading to inhibition of lysosomal enzymes including a-D-mannosidase. The mitogenic effect of a-D-mannosidase on lymphocytes has been studied. ... 

In a study of the secretion of lysosomal hydrolases by stimulated and non-stimulated macrophages from mice, a-D-mannosidase was found to be secreted in a considerable amount by a mechanism independent of phagocytosis. a-D-Mannosidase solubilized by 3M-LiCl from the cell walls of the coleop-tiles of Avena sativa has been purified via fractional precipitation, gel filtration, ion-exchange chromatography, and isoelectric focusing to homogeneity on disc gel electrophoresis. The enzyme (mol. wt. 6.3 x 10, pH optimum 4.5, 3.2 mM for 4-nitrophenyl a-D-mannopyranoside) had no metal ion... 

Since mannosido.se results from a genetically derrved absence of lysosomal a-mannosidase that leads to an accumulation of mannose-rich oligosaccharides, the effects of swainsonine (1) on this enzyme were investigated. The alkaloid, which bears a structural resemblance to the open-chain form of D-man nose (2), was in fact shown to be a reversible inhibitor of lysosomal a-mannosidase.8... 

Golgi a-l)-mannosidase II lysosomal mannosidase glycoprotein A-linked oligosaccharide processing [toxic, neurotoxic effects mimic hereditary lysosomal storage disease mannosidosis] (3-D-Glucuronidase cx-1-iduronidase Glucosidase... 

Berg, T., O. K. Tollersrud, S. U. Walkley, D. Siegel, and O. Nilssen, Purification of feline lysosomal a-mannosidase, determination of its cDNA sequence and identification of a mutation causing a-mannosidosis in Persian cats, Biochem. J., 1997, 328, 863-870. 

Gonzalez, D. S., Y. Kagawa, and K. W. Moremen, Isolation and characterization of the gene encoding the mouse broad specificity lysosomal a-mannosidase, Biochim. Biophys. Acta, 1999, 1445, 177-183,... 

Daniel, P. F., J. E. Evans, R. De Gasperi, B. Winchester, and C. D. Warren, A human lysosomal a(l-6)-mannosidase active on the branched trimannosyl core of complex glycans, Glycohiology, 1992, 2, 327-336. 

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