Glucosamine-6 Phosphate N-Acetyltransferase (GNPNAT1/GNA1)

  • James W. Dennis
Reference work entry


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).


Amino Sugar Guanidinium Hydrochloride Sperm Entry Hexosamine Biosynthesis Pathway Fungal Pathogen Candida Albicans 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alvarez FJ, Konopka JB (2007) Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans. Mol Biol Cell 18:965–975PubMedCentralPubMedCrossRefGoogle Scholar
  2. Boehmelt G, Fialka I, Brothers G, McGinley MD, Patterson SD, Mo R, Hui CC, Chung S, Huber LA, Mak TW et al (2000a) Cloning and characterization of the murine glucosamine-6-phosphate acetyltransferase EMeg32. J Biol Chem 275:12821–12832PubMedCrossRefGoogle Scholar
  3. Boehmelt G, Wakeham A, Elia A, Sasaki T, Plyte S, Potter J, Yang Y, Tsang E, Ruland J, Iscove NN et al (2000b) Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells. EMBO J 19:5092–5104PubMedCrossRefGoogle Scholar
  4. Breidenbach MA, Gallagher JE, King DS, Smart BP, Wu P, Bertozzi CR (2010) Targeted metabolic labeling of yeast N-glycans with unnatural sugars. Proc Natl Acad Sci USA 107:3988–3993PubMedCrossRefGoogle Scholar
  5. Broschat KO, Gorka C, Page JD, Martin-Berger CL, Davies MS, Huang Hc HC, Gulve EA, Salsgiver WJ, Kasten TP (2002) Kinetic characterization of human glutamine-fructose-6-phosphate amidotransferase I: potent feedback inhibition by glucosamine 6-phosphate. J Biol Chem 277:14764–14770PubMedCrossRefGoogle Scholar
  6. Bulik DA, Olczak M, Lucero HA, Osmond BC, Robbins PW, Specht CA (2003) Chitin synthesis in Saccharomyces cerevisiae in response to supplementation of growth medium with glucosamine and cell wall stress. Eukaryot Cell 2:886–900PubMedCentralPubMedCrossRefGoogle Scholar
  7. Cai L, Sutter BM, Li B, Tu BP (2011) Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell 42:426–437PubMedCentralPubMedCrossRefGoogle Scholar
  8. Dennis JW, Nabi IR, Demetriou M (2009) Metabolism, cell surface organization, and disease. Cell 139:1229–1241PubMedCentralPubMedCrossRefGoogle Scholar
  9. Grigorian A, Demetriou M (2010) Manipulating cell surface glycoproteins by targeting N-glycan-galectin interactions. Methods Enzymol 480:245–266PubMedCrossRefGoogle Scholar
  10. Grigorian A, Lee S-U, Tian W, Chen I-J, Gao G, Mendelsohn R, Dennis JW, Demetriou M (2007) Control of T cell mediated autoimmunity by metabolite flux to N-glycan biosynthesis. J Biol Chem 282:20027–20035PubMedCrossRefGoogle Scholar
  11. Hinderlich S, Berger M, Schwarzkopf M, Effertz K, Reutter W (2000) Molecular cloning and characterization of murine and human N-acetylglucosamine kinase. Eur J Biochem 267:3301–3308PubMedCrossRefGoogle Scholar
  12. Johnston WL, Dennis JW (2011) The eggshell in the C. elegans oocyte-to-embryo transition. Genesis 50:333–349PubMedCrossRefGoogle Scholar
  13. Johnston WL, Krizus A, Dennis JW (2006) The eggshell is required for meiotic fidelity, polar-body extrusion and polarization of the C. elegans embryo. BMC Biol 4:35PubMedCentralPubMedCrossRefGoogle Scholar
  14. Johnston WL, Krizus A, Dennis JW (2010) Eggshell chitin and chitin-interacting proteins prevent polyspermy in C. elegans. Curr Biol 20:1932–1937PubMedCrossRefGoogle Scholar
  15. Kreppel LK, Hart GW (1999) Regulation of a cytosolic and nuclear O-GlcNAc transferase. Role of the tetratricopeptide repeats. J Biol Chem 274:32015–32022PubMedCrossRefGoogle Scholar
  16. Krick R, Bremer S, Welter E, Schlotterhose P, Muehe Y, Eskelinen EL, Thumm M (2010) Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J Cell Biol 190:965–973PubMedCrossRefGoogle Scholar
  17. Lara-Lemus R, Calcagno ML (1998) Glucosamine-6-phosphate deaminase from beef kidney is an allosteric system of the V-type. Biochim Biophys Acta 1388:1–9PubMedCrossRefGoogle Scholar
  18. Lau K, Partridge EA, Silvescu CI, Grigorian A, Pawling J, Reinhold VN, Demetriou M, Dennis JW (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129:123–124PubMedCrossRefGoogle Scholar
  19. Laxman S, Tu BP (2010) Systems approaches for the study of metabolic cycles in yeast. Curr Opin Genet Dev 20:599–604PubMedCentralPubMedCrossRefGoogle Scholar
  20. Lee MH, Schedl T (2004) Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans. Genes Dev 18:1047–1059PubMedCrossRefGoogle Scholar
  21. Lin R, Allis CD, Elledge SJ (1996) PAT1, an evolutionarily conserved acetyltransferase homologue, is required for multiple steps in the cell cycle. Genes Cells 1:923–942PubMedCrossRefGoogle Scholar
  22. Marino K, Guther ML, Wernimont AK, Qiu W, Hui R, Ferguson MA (2011) Characterization, localization, essentiality, and high-resolution crystal structure of glucosamine 6-phosphate N-acetyltransferase from Trypanosoma brucei. Eukaryot Cell 10:985–997PubMedCentralPubMedCrossRefGoogle Scholar
  23. Mio T, Yamada-Okabe T, Arisawa M, Yamada-Okabe H (1999) Saccharomyces cerevisiae GNA1, an essential gene encoding a novel acetyltransferase involved in UDP-N-acetylglucosamine synthesis. J Biol Chem 274:424–429PubMedCrossRefGoogle Scholar
  24. Mkhikian H, Grigorian A, Li CF, Chen HL, Newton B, Zhou RW, Beeton C, Torossian S, Tatarian GG, Lee SU et al (2011) Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis. Nat Commun 2:334PubMedCentralPubMedCrossRefGoogle Scholar
  25. Oikawa S, Akamatsu N (1985) Three forms of rat liver glucosamine 6-phosphate acetylase and the changes in their levels during development. Int J Biochem 17:73–80PubMedCrossRefGoogle Scholar
  26. Oikawa S, Sato H, Akamatsu N (1986) Glucosamine 6-phosphate acetylase in rat ascites hepatomas. Int J Biochem 18:929–933PubMedCrossRefGoogle Scholar
  27. Peneff C, Mengin-Lecreulx D, Bourne Y (2001) The crystal structures of Apo and complexed Saccharomyces cerevisiae GNA1 shed light on the catalytic mechanism of an amino-sugar N-acetyltransferase. J Biol Chem 276:16328–16334PubMedCrossRefGoogle Scholar
  28. Porowski TS, Porowska H, Galasinski W (1990) Isolation, purification, and characterization of glucosamine-6-phosphate-N-acetylase from pig liver. Biochem Med Metab Biol 44:1–12PubMedCrossRefGoogle Scholar
  29. Sacristan C, Reyes A, Roncero C (2012) Neck compartmentalization as the molecular basis for the different endocytic behaviour of Chs3 during budding or hyperpolarized growth in yeast cells. Mol Microbiol 83:1124–1135PubMedCrossRefGoogle Scholar
  30. Sasai K, Ikeda Y, Fujii T, Tsuda T, Taniguchi N (2002) UDP-GlcNAc concentration is an important factor in the biosynthesis of beta1,6-branched oligosaccharides: regulation based on the kinetic properties of N-acetylglucosaminyltransferase V. Glycobiology 12:119–127PubMedCrossRefGoogle Scholar
  31. Smith TL, Rutter J (2007) Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation. Mol Cell 26:491–499PubMedCrossRefGoogle Scholar
  32. Vessal M, Hassid WZ (1973) Partial purification and properties of d-glucosamine 6-phosphate N-acetyltransferase from phaseolus aureus. Plant Physiol 51:1055–1060PubMedCentralPubMedCrossRefGoogle Scholar
  33. Vetting MW, LP SC, Yu M, Hegde SS, Magnet S, Roderick SL, Blanchard JS (2005) Structure and functions of the GNAT superfamily of acetyltransferases. Arch Biochem Biophys 433:212–226PubMedCrossRefGoogle Scholar
  34. Wang-Gillam A, Pastuszak I, Elbein AD (1998) A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase specificity from UDP-GalNAc to UDP-GlcNAc. J Biol Chem 273:27055–27057PubMedCrossRefGoogle Scholar
  35. Wang J, Liu X, Liang YH, Li LF, Su XD (2008) Acceptor substrate binding revealed by crystal structure of human glucosamine-6-phosphate N-acetyltransferase 1. FEBS Lett 582:2973–2978PubMedCrossRefGoogle Scholar
  36. Wellen KE, Lu C, Mancuso A, Lemons JM, Ryczko M, Dennis JW, Rabinowitz JD, Coller HA, Thompson CB (2010) The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 24:2784–2799PubMedCrossRefGoogle Scholar
  37. Xu G, Paige JS, Jaffrey SR (2010) Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat Biotechnol 28:868–873PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Joseph and Wolf Lebovic Health ComplexLunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalTorontoCanada

Personalised recommendations