ArticlePLoS genetics2012
UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play different roles in the development of Drosophila melanogaster.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Pathophysiology and targets for treatment in hereditary galactosemia: A systematic review of animal and cellular models.Journal of inherited metabolic disease · 2020Pooled it
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- Restoring galactose metabolism without restoring GALT rescues both compromised survival in larvae and an adult climbing deficit in a GALT-null D. Melanogaster model of classic galactosemia.Journal of inherited metabolic disease · 2024Article
- The mechanism ofiScience · 2024Article
- Long-chain acyl-CoA synthetase regulates systemic lipid homeostasis via glycosylation-dependent lipoprotein production.Life metabolism · 2024Article
- GALDAR: A genetically encoded galactose sensor for visualizing sugar metabolism in vivo.PLoS biology · 2024Article
- Molecular characterisation of Entamoeba histolytica UDP-glucose 4-epimerase, an enzyme able to provide building blocks for cyst wall formation.PLoS neglected tropical diseases · 2023Article
- Overexpression of UDP-sugar pyrophosphorylase leads to higher sensitivity towards galactose, providing new insights into the mechanisms of galactose toxicity in plants.The Plant journal : for cell and molecular biology · 2022Article
- Identifying susceptibility genes for primary ovarian insufficiency on the high-risk genetic background of a fragile X premutation.Fertility and sterility · 2021Article
- A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation.Development (Cambridge, England) · 2021Article
- Mechanistic Insights into Side Effects of Troglitazone and Rosiglitazone Using a Novel Inverse Molecular Docking Protocol.Pharmaceutics · 2021Article
- Galactosemia: Towards Pharmacological Chaperones.Journal of personalized medicine · 2021Review
- RNAi-Mediated Silencing of Pgants Shows Core 1Frontiers in physiology · 2021Article
- Association of UDP-galactose-4-epimerase with milk protein concentration in the Chinese Holstein population.Asian-Australasian journal of animal sciences · 2020Article
- Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE).Human molecular genetics · 2019Article
- Overexpression of UDP-Glucose 4-Epimerase Is Associated with Differentiation Grade of Gastric Cancer.Disease markers · 2019Article
- Article
- Drosophila melanogaster Models of Galactosemia.Current topics in developmental biology · 2017Review
- Coordinated movement, neuromuscular synaptogenesis and trans-synaptic signaling defects in Drosophila galactosemia models.Human molecular genetics · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In both humans and Drosophila melanogaster, UDP-galactose 4'-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.
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