AI Article Synopsis
- VLCAD deficiency is a genetic disorder in children that currently has no effective treatment options.
- Researchers discovered that treating VLCAD-deficient cells with a compound called S-nitroso-N-acetylcysteine can enhance the activity of mutant VLCAD enzymes.
- This treatment significantly improved the functioning of the cells by increasing VLCAD activity and correcting metabolic issues, suggesting a potential new approach for addressing the disorder.
Article Abstract
Very long acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic pediatric disorder presenting with a spectrum of phenotypes that remains for the most part untreatable. Here, we present a novel strategy for the correction of VLCAD deficiency by increasing mutant VLCAD enzymatic activity. Treatment of VLCAD-deficient fibroblasts, which express distinct mutant VLCAD protein and exhibit deficient fatty acid β-oxidation, with S-nitroso-N-acetylcysteine induced site-specific S-nitrosylation of VLCAD mutants at cysteine residue 237. Cysteine 237 S-nitrosylation was associated with an 8-17-fold increase in VLCAD-specific activity and concomitant correction of acylcarnitine profile and β-oxidation capacity, two hallmarks of the disorder. Overall, this study provides biochemical evidence for a potential therapeutic modality to correct β-oxidation deficiencies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400356 | PMC |
| http://dx.doi.org/10.1074/jbc.M114.635102 | DOI Listing |
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