Glucosamine-6 phosphate N-acetyltransferase (GNPNAT1/GNA1)

Abstract

UDP-GlcNAc is an essential high-energy donor for oligosaccharide biosynthesis in Bacteria, Archaea, and Eukaryota, suggesting the hexosamine biosynthesis pathway has very early origins. Fructose-6P, glutamine, and acetyl-CoA are required substrates, linking the hexosamine biosynthesis pathway to key metabolites of glycolysis, tricarboxylic acid cycle, lipogenesis, and nitrogen cycle. In vertebrates, UDP-GlcNAc is also the precursor to UDP-GalNAc and CMP-NeuNAc synthesis. These nucleotide sugars are utilized as high-energy donor substrates in most of the major pathways of protein glycosylation and glycolipid biosynthesis. UDP-GlcNAc is required in the biosynthesis of the N-glycosylation donor oligosaccharide-pp-dolichol as well as O-GlcNAcylation of cytosolic proteins. Concentrations of UDP-GlcNAc are rate limiting for O-GlcNAcylation (Kreppel and Hart 1999) and also in the Golgi for N-glycan remodeling on glycoproteins produced in the secretory pathway (Sasai et al. 2002).