Disease relevance of C00352

• Sequence analyses suggest that the NagB "superfamily" consists of three main clusters: multimeric and allosterically regulated glucosamine-6-phosphate deaminases (exemplified by Escherichia coli NagB), phosphogluconolactonases, and monomeric hexosamine-6-phosphate deaminases [1].
• To better understand the role of GlcN6P in solution structural dynamics and function, we have separated the glmS riboswitch core from Bacillus subtilis into a trans-cleaving ribozyme and an externally cleaved substrate [2].
• The recently described glmS ribozyme is a self-cleaving RNA sequence found in the 5' noncoding region of the transcript of the gene for glucosamine-6-phosphate (GlcN6P) synthase in many Gram-positive bacteria [3].
• Inactivation of glucosamine-6-phosphate synthetase from Salmonella typhimurium LT 2 SL 1027 by N beta-fumarylcarboxyamido-L-2,3-diamino-propionic acid [4].
• Epidermal growth factor (EGF), administered subcutaneously to neonatal mice at daily doses of 1,2 and 4 micrograms/g body weight for 3 days, significantly increased glucosamine-6-phosphate synthetase activity in the colon [5].

High impact information on C00352

• A glucosamine-6-phosphate N-acetylase-deficient mutant 3T3 line (AD6), however, aggregated randomly with parental 3T3 cells [6].
• GFA1 encodes L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) and catalyzes synthesis of glucosamine-6-phosphate [7].
• To identify the binding site of these phosphate esters, we took advantage of the homology of GKRP to the isomerase domain of GlmS (glucosamine-6-phosphate synthase) and created 12 different mutants of rat GKRP [8].
• Data base searches allowed us to identify an operon containing a putative kinase (YhfQ) belonging to the PfkB/ ribokinase family, a putative deglycase (YhfN), homologous to the isomerase domain of glucosamine-6-phosphate synthase, and a putative cationic amino acid transporter (YhfM) [9].
• Cloning and characterization of the murine glucosamine-6-phosphate acetyltransferase EMeg32. Differential expression and intracellular membrane association [10].

Chemical compound and disease context of C00352

• The glutamine amidohydrolase and fructose 6-phosphate binding domains of glucosamine-6-phosphate synthase from Escherichia coli have been overexpressed, purified and crystallized for X-ray diffraction analysis [11].
• Glutamate gamma-semialdehyde as a natural transition state analogue inhibitor of Escherichia coli glucosamine-6-phosphate synthase [12].
• Possible involvement of Lys603 from Escherichia coli glucosamine-6-phosphate synthase in the binding of its substrate fructose 6-phosphate [13].
• The isomerase activity of the C-terminal fructose-6P binding domain (residues 241-608) of glucosamine-6-phosphate synthase from Escherichia coli has been studied [14].
• Anticapsin, an active-site directed irreversible inhibitor of glucosamine-6-phosphate synthetase from Escherichia coli [15].

Biological context of C00352

• Glucosamine infusion induces insulin resistance in vivo, but the effect of glucosamine on intracellular metabolites of the hexosamine pathway, especially glucosamine-6-phosphate (GlcN6P) is unknown [16].
• A novel short-root gene encodes a glucosamine-6-phosphate acetyltransferase required for maintaining normal root cell shape in rice [17].
• This ribozyme is associated with the GlcN6P riboswitch, and ribozyme activity in response to binding of the metabolite, GlcN6P, is proposed to effect levels of gene expression [3].
• This mutant phenotype could also be suppressed by exogenously supplied glucosamine, N-acetylglucosamine, and galactosamine and to a lesser extent by glucosamine-6-phosphate, indicating that the nodM mutant bacteroids are limited for glucosamine [18].
• Analysis of suppressor mutations rendering the mutant independent of amino sugar supply revealed that the catabolic enzyme D-glucosamine-6-phosphate isomerase (deaminase), encoded by gene nagB of the nag operon, was able to fulfill anabolic functions in amino sugar biosynthesis [19].

Anatomical context of C00352

• Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6-phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine [20].
• Wild-type and mutated vectors were transfected into human embryonic kidney 293 cells and mesangial cells and GFAT enzyme activity was assessed by formation of glucosamine-6-phosphate [21].
• Purification and characterization of glucosamine-6-phosphate deaminase from dog kidney cortex [22].
• Due to the lack of glucosamine-6-phosphate the effective secretion of mannoprotein enzymes, acid phosphatase and invertase, by Candida albicans spheroplasts is inhibited [23].
• Suppression by thyroid hormones of glucosamine-6-phosphate synthetase activity in rat sublingual glands [24].

Associations of C00352 with other chemical compounds

• The rate-limiting step in glucosamine synthesis is the conversion of fructose-6-phosphate to glucosamine-6-phosphate by the enzyme glutamine:fructose-6-phosphate amidotransferase [25].
• Those authors showed that GlmM is a phosphoglucosamine mutase catalyzing interconversion of glucosamine-6-phosphate into glucosamine-1-phosphate, which is subsequently transformed into UDP-N-acetylglucosamine [26].
• Anticapsin: an active site directed inhibitor of glucosamine-6-phosphate synthetase from Candida albicans [27].
• Several analogs 5, 6, 7, 8, 10 and 11 of the C-terminal fragment of a peptide antibiotic Sch 37137 were designed and tested as inhibitors of glucosamine-6-phosphate synthase from Saccharomyces cerevisiae [28].
• On the other hand, three types of glycolyltransferase activities can be demonstrated in rodent livers, depending on either carnitine, glucosamine, or glucosamine-6-phosphate [29].

Gene context of C00352

• Candida albicans glucosamine-6-phosphate (GlcN-6-P) synthase was purified to apparent homogeneity with 52% yield from recombinant yeast YRSC-65 cells efficiently overexpressing the GFA1 gene [30].
• These results indicate that YFL017C specifies glucosamine-6-phosphate acetyltransferase; therefore, the gene was designated GNA1 (glucosamine-6-phosphate acetyltransferase) [31].
• Genetic complementation and enzyme assays have shown that the first of these, nagA, encodes N-acetyl glucosamine-6-phosphate deacetylase [32].
• The recently discovered glmS ribozyme is unique in that it functions as a glucosamine-6-phosphate (GlcN6P)-dependent catalyst believed to enable "riboswitch" regulation of amino-sugar biosynthesis in certain prokaryotes [33].
• Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium [34].

Analytical, diagnostic and therapeutic context of C00352

• Crystallization and preliminary X-ray analysis of the two domains of glucosamine-6-phosphate synthase from Escherichia coli [11].
• A site-directed mutagenesis of the GFA1 gene encoding Candida albicans glucosamine-6-phosphate (GlcN-6-P) synthase afforded its GFA1S208A version [35].
• Thyroidectomy caused a significant increase in glucosamine-6-phosphate synthetase activity [24].

References