A-Mannosidase lysosomal

Swainsonine (1) is of great biochemical interest since it is a potent and specific inhibitor of both lysosomal a-mannosidase and mannosidase II, which are involved in the cellular degradation of polysaccharides and in the processing of asparagine-linked glycoproteins, respectively [1]. 

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... 

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... 

L-rhamnosidase from Penicillium decumbers, inhibitor of, 319 lymphocytes, depression of, 11 lysosomal a-mannosidase (in cellular degradation of polysaccharides), inhibitor of, 319... 

Swainsonine reversibly inhibited macrophage lysosomal a-mannosidase (EC 3.2.1.24) in vitro (Greenaway et al. 1983). 

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. 

Tollersrud, O. K., T. Berg, P. Healy, G. Evjen, U. Ramachandran, and O. Nilssen, Purification of bovine lysosomal a-mannosidase, characterization of its gene and determination of two mutations that cause a- mannosidosis, Eur. J. Biochem., 1997, 246, 410-419. 

Pohlmann, R., A. Hasilik, S. Cheng, S. Pemble, B. Winchester, and K. von Figura, Synthesis of lysosomal a-mannosidase in normal and mannosidosis fibroblasts, Biochem. Biophys. Res. Commun., 1983, 115, 1083-1089. 

Riise, H. M., T. Berg, O. Nilssen, G. Romeo, O. K. Tollersrud, and I. Ceccherini, Genomic structure of the human lysosomal a-mannosidase gene (MANB), Genomics, 1997, 42, 200-207. 

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,... 

Gotoda, Y., N. Wakamatsu, H. Kawai, Y. Nishida, and T. Matsumoto, Missense and nonsense mutations in the lysosomal a-mannosidase gene (MANB) in severe and mild forms of a-mannosidosis. Am. J. Hum. Genet., 1998, 63, 1015-1024. 

Riise, H.M. Berg, T. Nilssen, O. Romeo, G. Tollersrud, O.K. Ceccherini, I. Genomic Structure of the Human Lysosomal a-Mannosidase Gene. (MANB). Genomics 1 >97, 42, 200-207. 

A number of mannosidase inhibitors have been isolated from various plants and fungi, and the specificity and activity of many of these inhibitors has been outlined in Table 1. The first glycoprotein processing inhibitor to be identified was the in-dolizidine alkaloid, swainsonine whose structure is presented in Figure 1B. Swain-sonine was shown to specifically inhibit plant and animal mannosidase II [78]. This alkaloid also inhibits lysosomal a-mannosidase and jack bean a-mannosidase, but... 

Berg, T. Tollersrud, O.K. Walkley, S.U. Siegel, D. Nilssen, O. 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. 

Tollersrud, O.K. Berg, T. Healy, P. Evjen, G. Ramachandran, U. Nilssen, O. Purification of Bovine Lysosomal a-Mannosidase, Characterization of its Gene and Determination of Two Mutations that Cause a-Mannosidosis. Ear. J. Biochem., 1997, 246-410—419. 

Marsh, C. A., and Gourlay, G. C., 1971, Evidence for a non-lysosomal a-mannosidase in rat liver homogenates, Biochim. Biophys. Acta 235 142. 

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