Sialic acids O-acetylation

N-Acylneuraminate-9(7)-0-acetyltransferase seems to be widespread in Nature, as sialic acids O-acetylated in the side chain are found in many animal species, including man (see Section II). However, enzyme activity has thus far been measured only in bovine, submandibular gland and in bovine serum. The 4-O-acetyltransferase appears... 

Sialic acid O-acetylation not only prevents (in the case of 4-O-acetylation) or much reduces (in the case of side-chain O-acetylation) the activity of viral, bacterial and animal (including trypanosomal) sialidases, but also impairs the activity of acylneuraminate-... 

One of the main functions of sialic acid O-acetyl groups is their inhibitory effect on the action of both sialidases and sialic acid-specific lyases [5,33]. While a 4-O-acetyl group completely hinders the action of these enzymes (with the exception of a slow release by viral sialidases [252]), such ester groups at the sialic acid side chain appreciably hinder hydrolysis of the glycosidic bond of these sugars and their further breakdown by lyases. The existence of esterases acting on O-acetylated sialic acids prior to sialidase is therefore a prerequisite or at least supports the rapid turnover of O-acetylated sialoglycoconjugates. The possibility of the existence of such enzymes was raised by the observation that... 

Sialic acids are acidic nine-carbon sugars that meet all the above discussed aspects and are special because the addition of sialic acid to glycoconjugates occurs exclusively at the non-reducing end. Because of this outstanding position, sialoglycoconjugates form the communication front of animal cells. Mandal and colleagues review this richness of the sialome with a focus on the O-acetylation of sialic acids. O-Acetylation represents a developmentally regulated modification and a marker of some cancer cells such as lymphoblasts in acute lymphoblastic leukemia. 

Kiehne, K., and Schauer, R. The influence of a- and P-galactose residues and sialic acid O-acetyl groups of rat erythrocytes on the interaction with peritoneal macrophages. Biol Chem. Hoppe-Seyler (1992) 373, 1117-1123. 

Higa, H.H., Butor, C., Diaz, S., and Varki,A. O-Acetylation and de-O-acetylation of sialic acids. O-Acetylation of sialic acids in rat liver Golgi apparatus involves an acetyl intermediate and essential histidine and lysine residues A transmembrane reaction. J. Biol. Chem. (1989) 264, 19427-19434. 

Equine sialic acid IV-acetyl-O-acetyl CisHaiNOio -59 183-187 23... 

Bovine sialic acid N -acetyl-O-aeetyl C.aHjiNO.o +8 134-137 23... 

Availability of substrate is an obvious regulatory factor in any enzyme-catalyzed reaction. In bisubstrate reaction it is important to consider the availability of each substrate, especially when they are synthesized in different compartments (e.g. sialyltransfer, requiring asialoacceptor and CMP-Neu5Ac). Coenzymes are particularly important in this respect, as they will also be substrates in other metabolic reactions. Thus, acetyl-CoA, ATP and CTP levels are important in sialic acid metabolism. Acetyl-CoA is required for the N- and O-... 

At least two species of sialic acid, V-acetyl- and N-glycolylneura-minic acids, have been identified in poultry serum, together with a very small amount of a third species, possibly A, 0-diacetylneuraminic acid (Faillard and Cabezas, 1%3 Dzulynska f u/., 1%9). The nest-cement-ing substance of the Chinese swiftlet, collocalia mucoid, is a glycoprotein containing V-acetyl-4-O-acetylneuraminic acid (Kathan and Weeks, 1969). 

Both forms of sialic acid, N-acetyl- and N-glycolylneuraminic acid (cf. Chapter 1), may coexist at the surface of the same cell, as shown in the murine TA3-Ha cancer cell by Codington et aL (1970). In the erythrocyte, the proportion ofN-acetyl- and N-glycolylneuraminic acid is similar to that of these compounds in other tissues, and varies with the animal species (Klenk, 1958a). No information is available at the present time on the occurrence and relative proportions of the O-acetyl derivatives of sialic acid at the surface of the mammalian cell. The absolute and relative amounts of sialic acid residues linked either to glycoproteins or to glycolipids vary widely and have been determined only on the erythrocytes of a few animal species (Uhlenbruck and Wintzer, 1970). 

TV-Acetyl neuraminic acid (NANA, O-Sialic acid, 5-acetamido-3,5-dideoxy-D-g/ycero-D-g/acto-2-nonulosonic acid, lactaminic acid) [I3I-48-6JM 309.3, m 159°(dec), 181-... 

As 2-amino-2-deoxy-D-mannose is tumorstatic and 2-acetamido-2-deoxy-D-mannose 6-phosphate is an obligatory intermediate in the biosynthetic pathway to sialic acid, displacement of the essential OH-6 with a fluorine atom should be interesting from the biological viewpoint. 2-Acetamido-1,3,4-tri-0-acetyl-2,6-dideoxy-6-fluoro-D-mannopyranose (see Table 111 in Section 11,3) and its O- and A,0-deacetyl derivatives were prepared the first compound showed weak anticancer activity. 

This enzyme [EC 4.1.3.3], also known as A-acetylneu-raminate aldolase, will convert A-acetylneuraminate to A-acetylmannosamine and pyruvate. The enzyme will also act on A-glycoloylneuraminate and on O-acetylated sialic acids, other than O -acetylated derivatives. 

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