Sialic acid-9-phosphate synthetase

Watson, D. R., Jordian, G. W., and Roseman, S. The sialic acids Sialic acid 9-phosphate synthetase. J. Biol Chem., 1966, 241, 5627-5636. 

Unlike the previous enzyme, NAN-aldolase, this enzyme catalyzes an essentially irreversible reaction in favor of synthesis. The enzyme was first found in rat liver extracts (Warren and Felsenfeld, 96 a) and has been purified some 95-fold from bovine submaxillary gland (Watson et aL, 1966). It can utilize both A -acetyl as well as N-glycolylmannosamine-6-P04. It seems likely that this enzyme, sialic acid-9-phosphate synthetase, catalyzes the major reaction for the synthesis of sialic acid. The product of the reaction is the 9-phosphate ester of sialic acid and must be dephosphorylated before activation can occur. 

In summary, there are three known pathways for the synthesis of sialic acid the NAN-aldolase, which condenses pyruvate and N-acylmannosamine (bacterial and animal) sialic acid-9-phosphate synthetase, which condenses phosphoenolpyruvate with AT-acylmannosa-mine-6-phosphate (animal tissue only) the enzyme from Neisseria meningitidis, which condenses N-acylmannosamine with phosphoenolpyruvate (bacteria only). 

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.

A synthetase purified from liver and submaxillary gland produces N-acetylneuraminic add 9-phosphate and Pj by condensing acetylmannosamine-6-phos-phate and phosphoenolpyruvic acid. Sialic acid is formed by the action of phosphatase on N-acetylneuraminic acid-9-phosphate. The biosynthetic pathway of sialic acid is summarized in Fig. 3-32. 

The final step in the activation of sialic acid to a nucleotide sugar occurs by the reaction shown above. It is clear that this reaction is unique in the sense that (1) the monosaccharide itself is the substrate rather than the more common 1-phosphate, and (2) the nucleotide sugar contains only one phosphate group rather than two. Like several of the other enzymes participating in sialic acid biosynthesis, CMP-sialic acid synthetase can utilize the N-glycolyl as well as the N-acetyl derivative. 

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