N-Acetylglucosamine Explained

N-Acetylglucosamine (GlcNAc) is an amide derivative of the monosaccharide glucose. It is a secondary amide between glucosamine and acetic acid. It is significant in several biological systems.

It is part of a biopolymer in the bacterial cell wall, which is built from alternating units of GlcNAc and N-acetylmuramic acid (MurNAc), cross-linked with oligopeptides at the lactic acid residue of MurNAc. This layered structure is called peptidoglycan (formerly called murein).

GlcNAc is the monomeric unit of the polymer chitin, which forms the exoskeletons of arthropods like insects and crustaceans. It is the main component of the radulas of mollusks, the beaks of cephalopods, and a major component of the cell walls of most fungi.

Polymerized with glucuronic acid, it forms hyaluronan.

GlcNAc has been reported to be an inhibitor of elastase release from human polymorphonuclear leukocytes (range 8–17% inhibition), however this is much weaker than the inhibition seen with N-acetylgalactosamine (range 92–100%).[1]

Medical uses

It has been proposed as a treatment for autoimmune diseases and recent tests have claimed some success.[2] [3]

O-GlcNAcylation

See main article: O-GlcNAc. O-GlcNAcylation is the process of adding a single N-acetylglucosamine sugar to the serine or threonine of a protein.[4] Comparable to phosphorylation, addition or removal of N-acetylglucosamine is a means of activating or deactivating enzymes or transcription factors. In fact, O-GlcNAcylation and phosphorylation often compete for the same serine/threonine sites. O-GlcNAcylation most often occurs on chromatin proteins, and is often seen as a response to stress.

Hyperglycemia increases O-GlcNAcylation, leading to insulin resistance.[5] Increased O-GlcNAcylation due to hyperglycemia is evidently a dysfunctional form of O-GlcNAcylation. O-GlcNAcylation decline in the brain with age is associated with cognitive decline. When O-GlcNAcylation was increased in the hippocampus of aged mice, spatial learning and memory improved.[6]

See also

References

  1. Kamel M, Hanafi M, Bassiouni M . Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine . Clinical and Experimental Rheumatology . 9 . 1 . 17–21 . 1991 . 2054963 .
  2. Grigorian A, Araujo L, Naidu NN, Place DJ, Choudhury B, Demetriou M . N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis . The Journal of Biological Chemistry . 286 . 46 . 40133–40141 . November 2011 . 21965673 . 3220534 . 10.1074/jbc.M111.277814 . free .
  3. Sy M, Newton BL, Pawling J, Hayama KL, Cordon A, Yu Z, Kuhle J, Dennis JW, Brandt AU, Demetriou M . 6 . N-acetylglucosamine inhibits inflammation and neurodegeneration markers in multiple sclerosis: a mechanistic trial . Journal of Neuroinflammation . 20 . 1 . 209 . September 2023 . 37705084 . 10498575 . 10.1186/s12974-023-02893-9 . free .
  4. Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O . Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease . Annual Review of Biochemistry . 80 . 825–858 . 2011 . 21391816 . 3294376 . 10.1146/annurev-biochem-060608-102511 .
  5. Ma J, Hart GW . Protein O-GlcNAcylation in diabetes and diabetic complications . Expert Review of Proteomics . 10 . 4 . 365–380 . August 2013 . 23992419 . 3985334 . 10.1586/14789450.2013.820536 .
  6. Wheatley EG, Albarran E, White CW, Bieri G, Sanchez-Diaz C, Pratt K, Snethlage CE, Ding JB, Villeda SA . 6 . Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain . Current Biology . 29 . 20 . 3359–3369.e4 . October 2019 . 31588002 . 7199460 . 10.1016/j.cub.2019.08.003 . free .

External links