Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014

MetaCyc Enzyme: glutamine:fructose-6-phosphate amidotransferase I

Gene: GFPT1 Accession Number: G-10017 (MetaCyc)

Species: Homo sapiens

Recombinant human glutamine:fructose-6-phosphate amidotransferase I was overexpressed in Escherichia coli and purified. However, its subunit structure was not reported [Broschat02]. The relative molecular mass of the subunit was determined by SDS-PAGE [McKnight92].

The enzyme is a member of the amidotransferase family, class II. It contains an N-terminal glutamine hydrolase domain and a C-terminal isomerase domain. It has a complex reaction mechanism that involves initial binding of fructose-6-phosphate, followed by glutamine binding. Released ammonia travels through a hydrophobic channel between the hydrolase and isomerase domains. The eukaryotic enzyme is a homotetramer, in contrast to the homodimeric prokaryotic enzyme. The pathway end product UDP-N-acetylglucosamine inhibits the in vitro activity of the eukaryotic, but not the prokaryotic, enzyme. Reviewed in [Milewski06].

The enzyme controls the flux of glucose into the hexosamine pathway. Increased production of the pathway end product UDP-N-acetylglucosamine has been implicated in the development of insulin resistance (in [Broschat02, McKnight92]).
A splice variant GFAT1Alt, and a second gene GFAT2 have been reported, although their physiological significance is not known (in [Broschat02].

Map Position: [69,405,911 <- 69,467,829]

Molecular Weight of Polypeptide: 78.806 kD (from nucleotide sequence), 77 kD (experimental) [McKnight92 ]

Unification Links: Entrez-gene:2673 , Mint:MINT-5001216 , PhosphoSite:Q06210 , PhylomeDB:Q06210 , Pride:Q06210 , Protein Model Portal:Q06210 , SMR:Q06210 , String:9606.ENSP00000354347 , UniProt:Q06210

Relationship Links: InterPro:IN-FAMILY:IPR000583 , InterPro:IN-FAMILY:IPR001347 , InterPro:IN-FAMILY:IPR005855 , InterPro:IN-FAMILY:IPR017932 , PDB:Structure:2V4M , PDB:Structure:2ZJ3 , PDB:Structure:2ZJ4 , Pfam:IN-FAMILY:PF00310 , Pfam:IN-FAMILY:PF01380 , Prosite:IN-FAMILY:PS51278 , Prosite:IN-FAMILY:PS51464

Gene-Reaction Schematic: ?

Created 20-Apr-2007 by Fulcher CA , SRI International

Enzymatic reaction of: glutamine:fructose-6-phosphate amidotransferase

Synonyms: glutamine-fructose-6-phosphate transaminase (isomerizing), GFAT, glucosamine-6-phosphate synthase

EC Number:

β-D-fructofuranose 6-phosphate + L-glutamine <=> D-glucosamine 6-phosphate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

In Pathways: UDP-N-acetyl-D-glucosamine biosynthesis II

Glutamine:fructose-6-phosphate amidotransferase catalyzes the first committed step in the cytoplasmic hexosamine biosynthetic pathway in eukaryotes. The enzyme is rate-limiting in this pathway (in [Broschat02]). The reaction is essentially irreversible and consists of two steps: transfer of the glutamine amide group to fructose-6-phosphate, and isomerization of fructose-6-phosphate to N-acetylglucosamine-6-phosphate. The enzyme is highly specific for L-glutamine and fructose-6-phosphate as substrates. Reviewed in [Milewski06].

The human enzyme has been shown to be feedback-inhibited by both UDP-N-acetyl-D-glucosamine, and glucosamine-6-phosphate. The transition state analog 2-amino-2-deoxyaminoglucitol 6-phosphate was a potent inhibitor. Less potent inhibitors included UDP-N-acetyl-D-galactosamine, N-acetyl-glucosamine-6-phosphate, and nucleotide monophosphates [Broschat02].

Inhibitors (Competitive): D-glucosamine 6-phosphate [Broschat02] , UDP-N-acetyl-α-D-glucosamine [Broschat02]

Inhibitors (Unknown Mechanism): UDP-N-acetyl-D-galactosamine [Broschat02] , N-acetyl-D-glucosamine 6-phosphate [Broschat02] , UMP [Broschat02] , dTMP [Broschat02] , CMP [Broschat02] , GMP [Broschat02] , AMP [Broschat02]

Kinetic Parameters:

Km (μM)
β-D-fructofuranose 6-phosphate


Broschat02: 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(17);14764-70. PMID: 11842094

McKnight92: McKnight GL, Mudri SL, Mathewes SL, Traxinger RR, Marshall S, Sheppard PO, O'Hara PJ (1992). "Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase." J Biol Chem 267(35);25208-12. PMID: 1460020

Milewski06: Milewski S, Gabriel I, Olchowy J (2006). "Enzymes of UDP-GlcNAc biosynthesis in yeast." Yeast 23(1);1-14. PMID: 16408321

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, biocyc13.