ArticleBiochimica et biophysica acta2013
Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 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
- Improvement of Mutant Galactose-1-Phosphate Uridylyltransferase (GALT) Activity by FDA-Approved Pharmacochaperones: A Preliminary Study.International journal of molecular sciences · 2025Article
- Brain function in classic galactosemia, a galactosemia network (GalNet) members review.Frontiers in genetics · 2024Review
- Classic Galactosemia: Clinical and Computational Characterization of a NovelInternational journal of molecular sciences · 2023Review
- Demonstrating the utility of sugar-phosphate phosphatases in coupled enzyme assays: galactose-1-phosphate uridylyltransferase as proof-of-concept.Glycobiology · 2023Article
- Review
- Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment.Biomolecules · 2022Review
- Novel mRNA therapy restores GALT protein and enzyme activity in a zebrafish model of classic galactosemia.Journal of inherited metabolic disease · 2022Article
- Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach.Molecules (Basel, Switzerland) · 2021Article
- Galactosemia: Towards Pharmacological Chaperones.Journal of personalized medicine · 2021Review
- Current and Future Treatments for Classic Galactosemia.Journal of personalized medicine · 2021Review
- Naturally-Occurring Rare Mutations Cause Mild to Catastrophic Effects in the Multifunctional and Cancer-Associated NQO1 Protein.Journal of personalized medicine · 2020Article
- Functional analysis ofJIMD reports · 2019Article
- Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.Orphanet journal of rare diseases · 2018Article
- Impaired fertility and motor function in a zebrafish model for classic galactosemia.Journal of inherited metabolic disease · 2018Article
- Sweet and sour: an update on classic galactosemia.Journal of inherited metabolic disease · 2017Review
- Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.Human molecular genetics · 2016Article
- UDP-galactose 4'-epimerase from the liver fluke, Fasciola hepatica: biochemical characterization of the enzyme and identification of inhibitors.Parasitology · 2015Article
- Compound heterozygosity with a novel S222N GALT mutation leads to atypical galactosemia with loss of GALT activity in erythrocytes but little evidence of clinical disease.Molecular genetics and metabolism reports · 2015Article
- Arginine Functionally Improves Clinically Relevant Human Galactose-1-Phosphate Uridylyltransferase (GALT) Variants Expressed in a Prokaryotic Model.JIMD reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Type I galactosemia is a genetic disorder that is caused by the impairment of galactose-1-phosphate uridylyltransferase (GALT; EC 2.7.7.12). Although a large number of mutations have been detected through genetic screening of the human GALT (hGALT) locus, for many it is not known how they cause their effects. The majority of these mutations are missense, with predicted substitutions scattered throughout the enzyme structure and thus causing impairment by other means rather than direct alterations to the active site. To clarify the fundamental, molecular basis of hGALT impairment we studied five disease-associated variants p.D28Y, p.L74P, p.F171S, p.F194L and p.R333G using both a yeast model and purified, recombinant proteins. In a yeast expression system there was a correlation between lysate activity and the ability to rescue growth in the presence of galactose, except for p.R333G. Kinetic analysis of the purified proteins quantified each variant's level of enzymatic impairment and demonstrated that this was largely due to altered substrate binding. Increased surface hydrophobicity, altered thermal stability and changes in proteolytic sensitivity were also detected. Our results demonstrate that hGALT requires a level of flexibility to function optimally and that altered folding is the underlying reason of impairment in all the variants tested here. This indicates that misfolding is a common, molecular basis of hGALT deficiency and suggests the potential of pharmacological chaperones and proteostasis regulators as novel therapeutic approaches for type I galactosemia.
Indexed as
Identifiers
What OpenQuestion holds
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.