Nucleotide sugars are the activated forms of monosaccharides. Nucleotide sugars act as glycosyl donors in glycosylation reactions. Those reactions are catalyzed by a group of enzymes called glycosyltransferases.
The anabolism of oligosaccharides - and, hence, the role of nucleotide sugars - was not clear until 1950s when Leloir and his coworkers found that the key enzymes in this process are the glycosyltransferases. These enzymes transfer a glycosyl group from a sugar nucleotide to an acceptor.
To act as glycosyl donors, those monosaccharides should exist in a highly energetic form. This occurs as a result of a reaction between nucleoside triphosphate (NTP) and glycosyl monophosphate (phosphate at anomeric carbon).
There are nine sugar nucleotides in complex animals which act as glycosyl donors and they can be classified depending on the type of the nucleoside forming them:
- Uridine Diphosphate: UDP-Glc, UDP-Gal, UDP-GalNAc, UDP-GlcNAc, UDP-GlcUA, UDP-Xyl
- Guanine Diphosphate: GDP-Man, GDP-Fuc.
- Cytosine Monophosphate: CMP-Neu5Ac, it is the only nucleotide sugar in the form of nucleotide monophosphate.
In plants and bacteria many other sugars are used and various donors are utilized for them. Specifically, CDP-glucose and TDP-glucose are found in nature and give rise to various other forms of CDP and TDP-sugar donor nucleotides.
listed below are the structures of some nucleotide sugars (example from each type).
Relationship between glycosylation pathways and different diseases
Normal metabolism of nucleotide sugars is very important. Any malfunction in any contributing enzyme will lead to a certain disease  for example:
- Inclusion body myopathy: is a congenital disease resulted from altered function of UDP-GlcNAc epimerase .
- Macular corneal dystrophy: is a congenital disease resulted from malfunction of GlcNAc-6-sulfotransferase.
- Congenital disorder in α-1,3 mannosyl transferase will result in a variety of clinical symptoms, e.g. hypotonia, psychomotor retardation, liver fibrosis and various feeding problems.
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- Cold Spring Harbor Laboratory Press Essentials of Glycobiology, Second Edition
- Samuel G, Reeves P (2003). "Biosynthesis of O-antigens: genes and pathways involved in nucleotide sugar precursor synthesis and O-antigen assembly". Carbohydr. Res. 338 (23): 2503–19. doi:10.1016/j.carres.2003.07.009. PMID 14670712.
- Xue M. He and Hung-wen Liu (2002). "Formation of unusual sugars: Mechanistic studies and biosynthetic applications". Annu Rev Biochem 71: 701–754. doi:10.1146/annurev.biochem.71.110601.135339. PMID 12045109.
- Encyclopedia of Biological Chemistry, Volume 2. 2004, Elsevier Inc. Hudson H. Freeze 302-307.
- "Nucleotide+sugars" "Nucleotide sugars" at the US National Library of Medicine Medical Subject Headings (MeSH)