Nucleotide sugar

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.

History
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.

Biological Importance
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).



Types
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.

Structures
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:
 * 1) Inclusion body myopathy: is a congenital disease resulted from altered function of UDP-GlcNAc epimerase.
 * 2) Macular corneal dystrophy: is a congenital disease resulted from malfunction of GlcNAc-6-sulfotransferase.
 * 3) 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.