Sugar nucleotides reactions

Regardless of the sugar and its origin, all monosaccharides must be activated by a kinase (reaction 1 below), or generated from a previously synthesized sugar nucleotide (reactions 2 and 3 below). 

We are familiar with several examples of chemical activation as a strategy for group transfer reactions. Acetyl-CoA is an activated form of acetate, biotin and tetrahydrofolate activate one-carbon groups for transfer, and ATP is an activated form of phosphate. Luis Leloir, a biochemist in Argentina, showed in the 1950s that glycogen synthesis depended upon sugar nucleotides, which may be... 

The net reaction for sugar nucleotide formation (combining the preceding two equations) is thus... 

Epimerization at C-5 of hexuronic acids is a reaction that proceeds both on the polymer and on the sugar nucleotide level. In addition to the three pairs of parent acids, namely, the u-glucolL-ido-, D manno/L-gulo-, and D-ga-lacto/L-altro-he uron c acids, the 2-amino-2-deoxy acids belonging to the last two and the 2,3-diamino-2,3-dideoxy acids belonging to the middle pair have been found. 

If processing occurs down to the core heptasaccharide (ManjiGIcNAclj), complex chains are synthesized by the addition of GIcNAc, removal of two Man, and the stepwise addition of individual sugars in reactions catalyzed by specific transferases (eg, GIcNAc, Gal, NeuAc transferases) that employ appropriate nucleotide sugars. 

The reaction is catalyzed by specific enzymes, usually termed204 sugar nucleotide pyrophosphorylases. The equilibrium constant is not far from unity, and addition of inorganic pyrophosphatase, an enzyme that converts inorganic pyrophosphate irreversibly into... 

The first application of this reaction for the synthesis of sugar nucleotides was reported in 1958, when Moffatt and Khorana269 prepared uridine 5 -(a-D-glucopyranosyl pyrophosphate) (5) in 59% yield from uridine 5 -phosphoramidate (58). Other examples of similar... 

It remains unclear whether or not the rate of cleavage of the gly-cosyl bond in sugar nucleotides depends upon the structure of the nucleotide residue, and the same uncertainty is true for other reactions that affect the glycosyl group no systematic kinetic studies have been reported. However, it may be noted that there appears to be no essential difference between the rates of acidic hydrolysis of the 5 -(a-D-glucopyranosyl pyrophosphates) of uridine and N3-methyluridine, 331... 

Conversion of the a-D-glucopyranosyl derivative (94a) into the a-D-galactopyranosyl ester (95a) was demonstrated370 in 1951 as the first example of an enzymic reaction of a sugar nucleotide. The enzyme that catalyzes this reaction, namely, uridine 5 -(a-D-glu-copyranosyl pyrophosphate) 4"-epimerase,371 is common in Nature. Purified preparations have been obtained from yeast,372 373 Escherichia coli 374-376 mung-bean seedlings,377 wheat germ,378 and animal tissues.244,379 380... 

Hydrolysis of sugar nucleotides with unspecific pyrophosphatases has already been mentioned (Section 11,1, p. 310). A similar reaction is catalyzed by a bacterial enzyme specific for adenosine 5 -(a-D-glucopyranosyl pyrophosphate).459 The specific conversion of uridine 5 -(a-D-glucopyranosyl pyrophosphate) into a-D-glucopyranosyl phosphate, uridine, and inorganic phosphate was observed with an enzyme from Escherichia colt 459,460 a preparation from Bacillus subtilis can act in a similar manner461 on different sugar nucleotides. ... 

One of the most impressive findings has been the discovery of lipid intermediates in the biosynthesis of polysaccharides (see Refs. 2 and 465.) At least two structurally different types of these compounds exist the intermediate may be an isoprenoid alcohol ester of the glycosyl pyrophosphate or the analogous derivative of the glycosyl phosphate. Derivatives of the first type are formed by reaction between the sugar nucleotide and the alcohol phosphate, for example, undecaprenyl phosphate (120), which participates in the biosynthesis of Salmonella lipopolysaccharide.466... 

Unlike the examples previously discussed, this interaction leads to splitting of the pyrophosphate linkage in the sugar nucleotide, with the liberation of nucleoside 5 -phosphate. Such reactions have been demonstrated for a-D-galactopyranosyl,468-488 2-acetamido-2-deoxy-a-D-glucopyranosyl,335,470 and pentapeptidyl-muramyl471,472 esters of uridine 5 -pyrophosphate. 

The diversity of the structures of naturally occurring sugar nucleotides and of their enzymic reactions has been described in this Chapter. The question now arises as to whether the recognition processes are unique for each enzyme-substrate pair, or whether there exist some common features between different enzymes in this respect. The latter possibility seems more attractive and, more importantly, it is supported by some experimental evidence. 

Direct experimental evidence for the existence of an ordered conformation of sugar nucleotides in solutions has been reported by Hirano,344 who observed characteristic optical-rotatory changes for a series of these compounds upon transition from water to concentrated urea solutions. The structural requirements for such an ordered conformation are still not clear. However, data at this point, based on indirect kinetic evidence from hydrogenation and hydroxylamin-olysis reactions (see Section IV, p. 360), seem to accord with the hypothetical model just described. Further studies on the conformations of sugar nucleotides in solution are highly desirable. 

The suitability of sugar nucleotides for biosynthetic reactions stems from several properties ... 

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