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Characterization of Gfat1 (zeppelin) and Gfat2, Essential Paralogous Genes Which Encode the Enzymes That Catalyze the Rate-Limiting Step in the Hexosamine Biosynthetic Pathway in Drosophila melanogaster.

Publication ,  Journal Article
Cotsworth, S; Jackson, CJ; Hallson, G; Fitzpatrick, KA; Syrzycka, M; Coulthard, AB; Bejsovec, A; Marchetti, M; Pimpinelli, S; Wang, SJH ...
Published in: Cells
January 2022

The zeppelin (zep) locus is known for its essential role in the development of the embryonic cuticle of Drosophila melanogaster. We show here that zep encodes Gfat1 (Glutamine: Fructose-6-Phosphate Aminotransferase 1; CG12449), the enzyme that catalyzes the rate-limiting step in the hexosamine biosynthesis pathway (HBP). This conserved pathway diverts 2%-5% of cellular glucose from glycolysis and is a nexus of sugar (fructose-6-phosphate), amino acid (glutamine), fatty acid [acetyl-coenzymeA (CoA)], and nucleotide/energy (UDP) metabolism. We also describe the isolation and characterization of lethal mutants in the euchromatic paralog, Gfat2 (CG1345), and demonstrate that ubiquitous expression of Gfat1+ or Gfat2+ transgenes can rescue lethal mutations in either gene. Gfat1 and Gfat2 show differences in mRNA and protein expression during embryogenesis and in essential tissue-specific requirements for Gfat1 and Gfat2, suggesting a degree of functional evolutionary divergence. An evolutionary, cytogenetic analysis of the two genes in six Drosophila species revealed Gfat2 to be located within euchromatin in all six species. Gfat1 localizes to heterochromatin in three melanogaster-group species, and to euchromatin in the more distantly related species. We have also found that the pattern of flanking-gene microsynteny is highly conserved for Gfat1 and somewhat less conserved for Gfat2.

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Published In

Cells

DOI

EISSN

2073-4409

ISSN

2073-4409

Publication Date

January 2022

Volume

11

Issue

3

Start / End Page

448

Related Subject Headings

  • Hexosamines
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
  • Glutamine
  • Euchromatin
  • Drosophila melanogaster
  • Biosynthetic Pathways
  • Animals
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

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Cotsworth, S., Jackson, C. J., Hallson, G., Fitzpatrick, K. A., Syrzycka, M., Coulthard, A. B., … Hilliker, A. J. (2022). Characterization of Gfat1 (zeppelin) and Gfat2, Essential Paralogous Genes Which Encode the Enzymes That Catalyze the Rate-Limiting Step in the Hexosamine Biosynthetic Pathway in Drosophila melanogaster. Cells, 11(3), 448. https://doi.org/10.3390/cells11030448
Cotsworth, Shawn, Catherine J. Jackson, Graham Hallson, Kathleen A. Fitzpatrick, Monika Syrzycka, Alistair B. Coulthard, Amy Bejsovec, et al. “Characterization of Gfat1 (zeppelin) and Gfat2, Essential Paralogous Genes Which Encode the Enzymes That Catalyze the Rate-Limiting Step in the Hexosamine Biosynthetic Pathway in Drosophila melanogaster.Cells 11, no. 3 (January 2022): 448. https://doi.org/10.3390/cells11030448.
Cotsworth S, Jackson CJ, Hallson G, Fitzpatrick KA, Syrzycka M, Coulthard AB, Bejsovec A, Marchetti M, Pimpinelli S, Wang SJH, Camfield RG, Verheyen EM, Sinclair DA, Honda BM, Hilliker AJ. Characterization of Gfat1 (zeppelin) and Gfat2, Essential Paralogous Genes Which Encode the Enzymes That Catalyze the Rate-Limiting Step in the Hexosamine Biosynthetic Pathway in Drosophila melanogaster. Cells. 2022 Jan;11(3):448.

Published In

Cells

DOI

EISSN

2073-4409

ISSN

2073-4409

Publication Date

January 2022

Volume

11

Issue

3

Start / End Page

448

Related Subject Headings

  • Hexosamines
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
  • Glutamine
  • Euchromatin
  • Drosophila melanogaster
  • Biosynthetic Pathways
  • Animals
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences