Nucleotide sugar

Nucleotide sugars are the activated forms of

Types

There are nine sugar nucleotides in humans which act as glycosyl donors and they can be classified depending on the type of the nucleoside forming them:^[7]

• Uridine Diphosphate:
  UDP-α-D-GlcNAc, UDP-α-D-GlcA
  , UDP-α-D-Xyl
• Guanosine Diphosphate:
  GDP-α-D-Man
  , GDP-β-L-Fuc.
• Cytidine Monophosphate: CMP-β-D-
  Neu5Ac
  ; in humans, it is the only nucleotide sugar in the form of nucleotide monophosphate.
• Cytidine Diphosphate: CDP-D-Ribitol (i.e. CMP-[ribitol phosphate]);^[8] though not a sugar, the phosphorylated sugar alcohol ribitol phosphate is incorporated into matriglycan as if it were a monosaccharide.

In other forms of life many other sugars are used and various donors are utilized for them. All five of the common nucleosides are used as a base for a nucleotide sugar donor somewhere in nature. As examples,

Structures

Listed below are the structures of some nucleotide sugars (one example from each type).

UDP-Gal	CMP-Neu5Ac	GDP-Man

Relationship to disease

Normal metabolism of nucleotide sugars is very important. Any malfunction in any contributing enzyme will lead to a certain disease [11] 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.

Relationship to drug discovery

The development of chemoenzymatic strategies to generate large libraries of non-native sugar nucleotides has enabled a process referred to as

• Carbohydrate chemistry
• EamA
• Glycorandomization
• Glycosyltransferase
• Nucleotide sugars metabolism

References