UDP-N-acetylgalactosamine

CMP-N-acetylneuraminic acid is formed by a series of reactions which are outgrowths of the pathways of hexosamine biosynthesis. As seen from Fig. 8A, N-acetylmannosamine can be regarded as the first specific intermediate in the biosynthesis of the nucleotide sugar and may be formed by 2-epimerization from either UDP-N-acetylglucosamine or N-acetylglucosamine. The mechanisms of these two reactions have recently been investigated and will be discussed below. 

It was suggested by Spivak and Roseman (1966) that since a short but distinct lag period occurred in the formation of UDP, the reaction possibly took place in two steps  

Further information concerning the reaction mechanism was obtained in recent experiments by Salo and Fletcher (1970a,b). To examine the hypothesis that UDP-N-acetylmannosamine is an intermediate in the reaction, this nucleotide sugar was synthesized chemically (Salo and Fletcher, 1970a), and on incubation with UDP-N-acetylglucosamine 2-epimerase, cleavage to UDP and N-acetylmannosamine did indeed 

The DPN requirement indicated in the reaction scheme is still entirely hypothetical. No enhancement of activity was observed on addition of DPN or TPN, but since many epimerases may contain tightly bound DPN, the postulated reaction mechanism is entirely plausible. 

The question whether one or two enzymes are involved in the epimeri-zation has not been conclusively resolved by the studies of Salo and Fletcher, but the data support the view that the reaction is catalyzed by only one enzyme. 

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Okajima T, Nakamura Y, Uchikawa M, Haslam DB, Nu-mata SI, Furukawa K, Urano T. Expression cloning of human 60. globoside synthase cDNAs. Identification of beta 3Gal-T3 as UDP-N-acetylgalactosamine globotriaosylceramide beta 1,3-N-acetylgalactosaminyltransferase. J. Biol. Chem. 2000 275 40498-40503. 

Yanagisawa K, Taniguchi N, Makita A (1987) Purification and properties of GM2 synthase, UDP-N-acetylgalactosamine GM3 jS-N-acetyl-galactosaminyltransferase from rat liver. Biochim Biophys Acta 919 213-220... 

See also Biosynthesis of Glycoconjugates, Glycoproteins (from Chapter 9), Glycosaminoglycans, Hyaluronic Acid, Structural Polysaccharides, UDP-N-Acetylgalactosamine... 

UDP-N-acetylglucosamine UDP-N-acetylgalactosamine CMP-N-acetyIneuraminic acid GDP-fucose GDP-mannose... 

In the biosynthesis of A. s., the amino group is supplied by transamination from glutamine. Fructose 6-phosphate is aminated to D-glucosamine 6-phosphate by a hexose-phosphate transaminase. Glucosamine phosphate can then be converted by a transacetylase into the N-acetyl derivative. The latter is isomerized to the 1-phosphate, then activated by reaction with UTP, to form UDP-N-acetylglucosamine, which can be isomerized to UDP-N-acetylgalactosamine. See Muramic acid. Neuraminic acid. 

Hill, H. D., Schwyzer, M., Steinman, H. M., and Hill, R. L., 1977b, Ovine submaxillary mucin— Primary structure and peptide substrates of UDP-N-acetylgalactosamine Mucin transferase, J. Biol. Chem. 252 3799-3804. 

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