UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) is the source of the first two GlcNAc moieties added during N-linked glycosylation of proteins and provides GlcNAc for synthesis of GPI anchors. In yeast, it is synthesized from fructose-6-phosphate (F6P) by the consecutive action of Gfa1p, Gna1p, Pcm1p, and Qri1p, although a different pathway (4, 5) is used in bacteria. UDP-GlcNAc is also the building block from which chitin, a linear polymer of beta-1,4-N-acetylglucosamine, is constructed. Chitin is a component of the cell wall deposited as a ring around the neck of the growing bud during cell division. Bud scars, the remnants of the chitinous primary septum seen on the surface of mother cells after division, are the primary repository of chitin (reviewed in 6).

GFA1 encodes glutamine:fructose-6-phosphate amidotransferase (GFAT, EC 2.6.1.16), which converts F6P to glucosamine-6-phosphate. Originally called gcn1 (1, 7), mutants are auxotrophic for glucosamine (7), fail to complete sporulation (7, 8), and have altered glycoprotein synthesis (8).

GFA1 is regulated by many of the mechanisms that control the cell cycle. It is induced in response to mating pheromones (1) and the PKC1 MAP kinase cascade (9), and negatively regulated by Glc7p (9). The promoter contains functional binding sites for Mcm1p (10) and Ste12p (11). GFA1 is also induced by perturbation of the cell wall (2, 12, 13), as is chitin synthesis, but only chitin synthesis is induced when glucosamine (which enters the cell as glucosamine-6-P, bypassing Gfa1p) is added to the growth medium (12).

Humans have two enzymes with GFAT activity: Gfpt1 (OMIM) and Gfpt2 (OMIM). Methylmercury (MeHg), a potent toxin to yeast and to humans, targets GFAT in both yeast and human cells (14); overexpression of GFA1 provides resistance by titrating MeHg, not by increasing the strength of the cell wall (14, 15). Candida albicans GFA1 complements deletion of GFA1 in S. cerevisiae (16).

Last updated: 2005-07-01