Glycoproteins nucleotide sugars

The Biosynthesis of O-Linked Glycoproteins Uses Nucleotide Sugars... 

Several nucleotides have been detected in milk (see Table 1.9). The list includes the common mono-and dinucleotides, 3, 5 cyclic AMP, and adenosine triphosphate (ATP). The ATP is located entirely in the casein micelles (Richardson et al. 1980). Several nucleotide sugars, undoubtedly excess intermediates left over from mammary synthesis of glycoproteins, are present. Both DNA and RNA have been detected in milk (Swope and Brunner 1965 Swope et al. 1965 Langen 1967) they are probably found primarily in milk leukocytes. 

Figure 4 Overview of mucin-type 0-linked glycoprotein biosynthesis. The production of the eight core structures found in 0-glycans is shown along with the enzymes and nucleotide sugars that are involved in each step. Additional information on the enzymes shown can be found in the KEGG databases (see the Legend for Fig. 3).

Biosynthetic pathways for nucleotide sugars. [Reproduced with permission from H. Schachter, Glycoprotein biosynthesis. In The Glycoconjugates, Vol. 2, M.I. Horowitz and W. Pigman (Eds). Academic Press,... 

Trombetta, E. S., and Helenius, A. (1999). Glycoprotein reglucosylation and nucleotide sugar utilization in the secretory pathway Identification of a nucleoside diphosphatase in the endoplasmic reticulum. EMBO J. 18, 3282-3292. 

Sialyltransferases. In eukaryotic cells, addition of terminal sialic acid to glycoconjugates is carried out by specific enzymes called sialyltransferases (STs). STs catalyze the transfer of a sialic acid from the activated nucleotide sugar donor CMP-N-acelylneuraminic acid (CMP-NeuSAc) to the terminal nonreducing position of oligosaccharide chains either of glycoproteins or glycolipids. 

In the overwhelming majority of cases, the nucleotide sugars appear to be the immediate precursors of the glycoprotein-bound sugars, but evidence has been accumulating in recent years for the participation of lipid intermediates in certain of the biosynthetic reactions. In particular, incorporation of mannose into glycoproteins may take place via a lipid intermediate, and the details of this process will be discussed later (see Section IV, A, 5, b). 

It is now well established that several monosaccharides can be utilized as precursors of plasma glycoproteins after administration to the whole animal or to the perfused liver. The sugars are n-glucose, n-glucosamine, L-fucose, D-galactose, n-mannose, and n-galactosamine. Monosaccharides must be converted to their respective nucleotide sugars prior to incorporation and the pathways for these conversions are discussed in Section III. 

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