ArticleMolecular genetics and metabolism2008
Distinct roles of galactose-1P in galactose-mediated growth arrest of yeast deficient in galactose-1P uridylyltransferase (GALT) and UDP-galactose 4'-epimerase (GALE).
Article in Molecular genetics and metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 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
- Cytosolic UDP-Gal biosynthetic machinery is required for dimerization of SLC35A2 in the Golgi membrane and its interaction with B4GalT1.Frontiers in molecular biosciences · 2025Article
- Studying microbial triglyceride production from corn stover saccharides unveils insights into the galactose metabolism of Ustilago maydis.Microbial cell factories · 2024Article
- Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.JIMD reports · 2024Article
- Article
- Sphingolipid depletion suppresses UPR activation and promotes galactose hypersensitivity in yeast models of classic galactosemia.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- 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
- Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.Journal of medicinal chemistry · 2021Article
- Pathophysiology and management of classic galactosemic primary ovarian insufficiency.Reproduction & fertility · 2021Review
- Chromatin regulatory genes differentially interact in networks to facilitate distinct GAL1 activity and noise profiles.Current genetics · 2021Article
- Antifungal Activity of 1,4-Dialkoxynaphthalen-2-Acyl Imidazolium Salts by Inducing Apoptosis of PathogenicPharmaceutics · 2021Article
- Galactosemia: Towards Pharmacological Chaperones.Journal of personalized medicine · 2021Review
- New Pyrimidinone-Fused 1,4-Naphthoquinone Derivatives Inhibit the Growth of Drug Resistant Oral Bacteria.Biomedicines · 2020Article
- The birth, evolution and death of metabolic gene clusters in fungi.Nature reviews. Microbiology · 2018Review
- Antifungal activity of magnoflorine against Candida strains.World journal of microbiology & biotechnology · 2018Article
- Insights into Bidirectional Gene Expression Control Using the Canonical GAL1/GAL10 Promoter.Cell reports · 2018Article
- Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt.Journal of advanced research · 2018Article
- Sweet and sour: an update on classic galactosemia.Journal of inherited metabolic disease · 2017Review
- Hsp90 Maintains Proteostasis of the Galactose Utilization Pathway To Prevent Cell Lethality.Molecular and cellular biology · 2016Article
- Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes.Applied and environmental microbiology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Galactose is metabolized in humans and other species by the three-enzyme Leloir pathway comprised of galactokinase (GALK), galactose 1-P uridylyltransferase (GALT), and UDP-galactose 4'-epimerase (GALE). Impairment of GALT or GALE in humans results in the potentially lethal disorder galactosemia, and loss of either enzyme in yeast results in galactose-dependent growth arrest of cultures despite the availability of an alternate carbon source. In contrast, loss of GALK in humans is not life-threatening, and in yeast has no impact on the growth of cultures challenged with galactose. Further, the growth of both GALT-null and GALE-null yeast challenged with galactose is rescued by loss of GALK, thereby implicating the GALK reaction product, gal-1P, for a role in the galactose-sensitivity of both strains. However, the nature of that relationship has remained unclear. Here we have developed and applied a doxycycline-repressible allele of galactokinase to define the quantitative relationship between galactokinase activity, gal-1P accumulation, and growth arrest of galactose-challenged GALT or GALE-deficient yeast. Our results demonstrate a clear threshold relationship between gal-1P accumulation and galactose-mediated growth arrest in both GALT-null and GALE-null yeast, however, the threshold for the two strains is distinct. Further, we tested the galactose-sensitivity of yeast double-null for GALT and GALE, and found that although loss of GALT barely changed accumulation of gal-1P, it significantly lowered the accumulation of UDP-gal, and also dramatically rescued growth of the GALE-null cells. Together, these data suggest that while gal-1P alone may account for the galactose-sensitivity of GALT-null cells, other factors, likely to include UDP-gal accumulation, must contribute to the galactose-sensitivity of GALE-null cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.