Uridine diphosphate N-acetylglucosamine
Chemical compound
From Wikipedia, the free encyclopedia
Uridine diphosphate N-acetylglucosamine or UDP-GlcNAc is a nucleotide sugar and a coenzyme in metabolism. It is used by glycosyltransferases to transfer N-acetylglucosamine residues to substrates. UDP-GlcNAc is used for making glycosaminoglycans, proteoglycans, and glycolipids.[1] D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars.[2] To be specific, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine[3] as the first step of the hexosamine biosynthesis pathway.[4] The end-product of this pathway is UDP-GlcNAc. Some enzymes involved in the biosynthesis of UDP-GlcNAc vary between prokaryotic and eukaryotic organisms, serving as potential drug targets for antibiotic development.[5]
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| Names | |
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| IUPAC name
Uridine 5′-(2-acetamido-2-deoxy-α-D-glucopyranosyl dihydrogen diphosphate) | |
| Systematic IUPAC name
O1-[(2R,3R,4R,5S,6R)-3-Acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl] O3-{[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]methyl} dihydrogen diphosphate | |
| Other names
UDP-N-acetylglucosamine; UDP-GlcNAc | |
| Identifiers | |
3D model (JSmol) |
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CompTox Dashboard (EPA) |
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| Properties | |
| C17H27N3O17P2 | |
| Molar mass | 607.355 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Biosignaling
UDP-GlcNAc is extensively involved in intracellular signaling as a substrate for O-linked N-acetylglucosamine transferases (OGTs) to install the O-GlcNAc post-translational modification in a wide range of species. It is also involved in nuclear pore formation and nuclear signalling. OGTs and OG-ases play an important role in the structure of the cytoskeleton. In mammals, there is enrichment of OGT transcripts in the pancreas beta-cells, and UDP-GlcNAc is thought to be part of the glucose sensing mechanism. There is also evidence that it plays a part in insulin sensitivity in other cells. In plants, it is involved in the control of gibberellin production.[6] In eukaryotic stem cells, the presence of UDP-GlcNAc is essential for maintaining pluripotency, which is sustained through O-GlcNAcylation.[7]
Clostridium novyi type A alpha-toxin is an O-linked N-actetylglucosamine transferase acting on Rho proteins and causing the collapse of the cytoskeleton.
There is a possible relationship between the inhibition of oxidative phosphorylation and reduced UDP-GlcNAc levels.[7]
Prokaryotic and eukaryotic biosynthesis
UDP-GlcNAc biosynthesis is not regulated by the same enzymes in prokaryotic and eukaryotic organisms. The lack of the bifunctional GlmU acetyltransferase and pyrophosphorylase in eukaryotes makes it a possible target for blocking UDP-GlcNAc synthesis (an essential precursor for peptidoglycan synthesis) in bacteria without affecting host cells.[5]