Mannose-rich oligosaccharides

Genetic mannosidosis has been described in man, Angus cattle and Murray Gray cattle, and is characterized by a deficiency of a-mannosidase leading to storage of excess mannose-rich oligosaccharides in lysosomes. Pathologically, there is vacuolation of reticuloendothelial cells in the liver and lymph nodes, pancreatic exocrine cells, and neurons. Affected cattle are ataxic, uncoordinated, fail to thrive, and die in the first year of life. 

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... 

A detailed spectroscopic study has shown that swainsonine, from Swainsona canescens (Benth.) A. Lee, is 8a/3-indolizidine-la,2a,8 3-triol (1), and the structure and relative configuration have been confirmed by X-ray crystallography.1 Swainsonine is a potent inhibitor of a-mannosidase, and in animals it produces an accumulation of mannose-rich oligosaccharides in the lysosomal system of cells, leading to organ dysfunction and clinical disease.1... 

The B-chain is a lectin which binds to galactose residues present in cell surface receptors. There are two binding sites with different affinities for galacfose. Additionally, fhe B-chain also confains mannose-rich oligosaccharides which can become bound to mannose receptors on the surface of reticulo-endothelial cells. The binding of fhe B-chain to the cell surface acts as an anchor and facilitates the entry of the A-chain into the cell. 

Fig. 13 Glycoprofiling of placental and glycoengineered hCG based on the binding of specific lectins. Lectins specific for a2,3/6-bound sialic acids (black bars SNA, Sambucus nigra agglutinin), a2,6-bound sialic acids (grey bars PSL, Polyporus squamosus lectin) and mannose-rich oligosaccharides (white bars GNL Galanthus nivalis lectin).

Mannosidosis (an oligosaccharidosis). a-Mannosidase (EC 3.2.1.24). Accumulation of mannose-rich, glucosamine-containing oligosaccharides. Brain damage, bone abnormalities, opaque cornea and cataracts, hepatosplenomegaly. Skeletal involvement and facial features similar to Hurler s syndrome (below). 

The number of potential glycosylation sites in the different NAs varies from 3 to 7, and NA contains mannose-rich as well as complex oligosaccharides. Glycosylation at a specific site has been correlated with the unique growth properties and virulence of the WSN strain of influenza virus (Schulman and Palese,1977 Li et al., 1993). In contrast to HA, influenza NA does not undergo any proteolytic processing. 

The cell wall of the yeast Saccharomyces is rich in mannoproteins that contain 50-90% mannose.264 The 250-residue mannan chains consist of an a-1,6-linked backbone with mono-, di-, and tri-mannosyl branches. These are attached to the same core structure as that of mammalian oligosaccharides. All of the core structures are formed in a similar way.258 265 The mannoproteins may serve as a "filler" to occupy spaces in a cell wall constructed from P-1,3- and P-l,6-linked gly-cans and chitin. All of the four components, including the mannoproteins, are covalently linked together.266 As was emphasized in Chapter 4 (pp. 186-188)... 

N-Glycosidically linked oligosaccharides. The oligomannosidic type is rich in mannose residues, whereas the complex type contains carbohydrate residues in the outer domain. Both types have a common core. 

The bond to L-asparagine takes place via an oligosaccharide rich in mannose 13.20, which is probably the same as in glycoproteins. On the other hand, the most frequent core structure on L-serine and L-threonine, 13.29, is entirely different. The reader should note the jS-D-xylopyranosyl and jS-D-glucuronopyranosyl units. The long chain is linked to 0-4 of the j3-D-glucoronopyranosyl unit. We will come back to these structures in Chapter 17, while on the subject of heparin, which belongs to this family. 

The RTA chain can be obtained from RT using the procedure depicted in Fig. 5. RTA contains a complex oligosaccharide unit rich in mannose that is... 

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