Uridine diphosphate ''N''-acetylglucosamine or UDP-GlcNAc is a nucleotide sugar and a

coenzyme A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can ...

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

. It is used by glycosyltransferases to transfer ''N''-acetylglucosamine residues to substrates. UDP-GlcNAc is used for making

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...

proteoglycans Proteoglycans are proteins that are heavily glycosylation, glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalent bond, covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a ...

, and glycolipids. D-Glucosamine is made naturally in the form of glucosamine-6-phosphate, and is the biochemical precursor of all nitrogen-containing sugars. To be specific, glucosamine-6-phosphate is synthesized from

fructose 6-phosphate Fructose 6-phosphate (sometimes called the Neuberg ester) is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells ...

and

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

as the first step of the

hexosamine Hexosamines are amino sugars created by adding an amine group to a hexose. Examples include: * Fructosamine (based upon fructose) * Galactosamine (based upon galactose) * Glucosamine (based upon glucose) * Mannosamine (based upon mannose Man ...

biosynthesis pathway. The end-product of this pathway is UDP-GlcNAc. Some enzymes involved in the biosynthesis of UDP-GlcNAc vary between

prokaryotic A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

and

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

organisms, serving as potential drug targets for antibiotic development.

Biosignaling

UDP-GlcNAc is extensively involved in

intracellular signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

as a substrate for ''O''-linked ''N''-acetylglucosamine transferases (OGTs) to install the ''O''-GlcNAc

post-translational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...

in a wide range of species. It is also involved in

nuclear pore The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tran ...

formation and nuclear signalling. OGTs and OG-ases play an important role in the structure of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

. In mammals, there is enrichment of OGT transcripts in the

pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...

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 Gibberellins (GAs) are plant hormones that regulate various Biological process, developmental processes, including Plant stem, stem elongation, germination, dormancy, flowering, flower development, and leaf and fruit senescence. They are one of th ...

production. In eukaryotic

stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

, the presence of UDP-GlcNAc is essential for maintaining

pluripotency Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...

, which is sustained through O-GlcNAcylation. '' 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.

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.

References

{{Purinergics Metabolism Coenzymes