Glucose to Sialic Acid

FIGURE 2. Major anabolic reactions leading to the synthesis of sialic acid and sialic-acid- 

Roseman et al. (1958) purified the enzyme from microbial and mammalian extracts and demonstrated that fructose-6-phosphate, and not glucose-6-phosphate, was the required substrate. Ghosh et al. (1969) purified the enzyme from Neurospora crassa, E. coli, and rat liver until it was free from phosphoglucose isomerase and glutaminase. Using this more purified enzyme preparation, fructose-6-phosphate was shown to be the required substrate, and a 1 1 stoichiometry was demonstrated for glutamine and fructose-6-phosphate. 

The apparent discrepancy between the findings of Pogell and Roseman have never adequately been resolved, although Winterbum and Phelps (1970, Wl a,b,c) have verified that fructose-6-phosphate is the true substrate for the rat liver enzyme. It is still possible that besides these, other transamidase enzymes exist. 

An alternate enzymatic route for the biosynthesis of glucosamine-6-phosphate is the reversal of a reaction catalyzed by glucosamine-6-phosphate deaminase. 

Leloir and Cardini (1956) first found an enzyme in pig kidney cortex which catalyzed the synthesis of glucosamine-6-phosphate. The equilibrium of the enzyme reaction is strongly in favor of deamination. However, Comb and Roseman (1958a) showed that by coupling to a second enzyme (acetylase) the reaction can be pulled in the direction of synthesis. This enzyme (deaminase) apparently is ubiquitous and is stimulated by the presence of A -acetylglucosamine-6-phosphate. 

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