Enzymes, sialylated

Heptasaccharide 62 was obtained from hexasaccharide 56 (see Section V,2). As in the case of D-galactosylation, enzymic sialylation turned out to be highly regioselective, leading to a single compound, whereas each galactose... 

In brief, glycosidation systems similar to that depicted in Fig. 10.3, with regeneration of sugar nucleotides, have been developed with UDP GIcNAc, GDP Man, GDP Fuc, UDP GlcUA, and CMP NeuSAc. Enzymic sialylation will be described in detail in Section 12.4. 

The chemoenzymic synthesis of trimeric SiaLe decasaccharide 49 was achieved by enzymically sialylating and fucosylating the linear hexamer. The analogue... 

This set of enzymes consists of those proteins that catalyze the transfer of sialyl moieties. (1) CMP-A-acetyl-neuraminate-j8-galactoside o -2,6-sialyltransferase [EC... 

Figure 2.19 Sialylation ofN-acetyl lactose by cytidyl monophosphate-N-acetylneuraminic acid using Of 2,3-neuraminic acid transferase as catalyst (upper box). Regeneration of the sugar nucleotide is shown in the lower box. CMP is converted into CTP in two steps using two different kinases. In the final step CMP-A -acetylneuraminic acid is synthesised from CTP and A -acetylneuraminic acid (sialic acid) using the appropriate synthetase. The formed pyrophosphate is converted into inorganic phosphate. Altogether five different enzymes are involved in the process.

Substrate-specificity studies on microsomal, frog-liver sialyltrans-ferase revealed the presence of (2—>3) and (2—>6) activities.277 This enzyme system readily sialylates oligosaccharides, but is almost inactive with asialofetuin, which is in contrast to the sialylation of oligosaccharides, as well as asialofetuin, by rat-liver sialyltransferase.278 The conclusion from this observation is that acceptor specificity of sialyl-transferases isolated from liver of evolutionary distant animals is similar for substrates of low molecular weight, but differs for compounds of high molecular weight.279... 

Apart from the 4-O-acetylated sialic acids, another sialidase-resist-ant sialic acid exists in Nature, namely, the internal, Gal-bound, sialic acid residue of GM,. In contrast to this side-positioned sialic acid, the sialyl residues bound to the peripheral Gal of gangliosides, or to both the peripheral and the internal sialic acid residues forming oligo-sialvl chains in several members of the large ganglioside family,la can be readily removed by sialidases, as was tested with viral, bacterial, and mammalian enzymes.35 -35 1... 

The internal, sialyl residue of GM, is not completely resistant to some sialidases, so long as the oligosaccharide chain is bound to the ceramide part of GM, it is slowly cleaved by C. perfringens sialidase in the presence of bile salts.77 57 3511 Surprisingly, it is a relatively good substrate for the A. ureafaciens sialidase.360 Rapid hydrolysis of GM, sialic acid has also been observed with Sendai virus sialidase, in contrast to the enzymes from NDV or influenza viruses.361 Susceptibility towards mammalian sialidases has also been reported.362 However, it... 

The internal, sialic acid residue of GMj or GM2 is readily susceptible to sialidase action after enzymic release of the peripheral Gal and GalNAc residues, leading to GM3 having a terminal sialyl residue, and this represents the natural pathway of the catabolism of ganglio-sides.110 354 355... 

The frequent occurrence of sialylated enzymes, or even of multiple forms, which are sometimes tissue-dependent, with a varying number of sialyl residues as, for example, in y-glutamyltranspeptida.se (EC 2.3.2.2),456,457 is not yet fully understood. Although the activity of most of these enzymes is not influenced by removal of sialic acid,454 the activity of monoamine oxidase A (EC 1.4.3.4) of outer mitochondrial membranes of rat liver has been shown to be destroyed by treatment with sialidase438 the substrate specificity of acetylcholinesterase (EC 3.1.1.7) is altered,459 the kinetic properties of human acid and alkaline phosphatases (EC 3.1.3.1 and 3.1.3.2) are changed, and the stability of a-D-galactosidase (EC 3.2.1.22) is drastically lowered.415 In these cases, an influence of sialyl residues on the conformation of the enzyme is assumed, but awaits firm evidence. 

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