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Strategies for correcting very long chain acyl-CoA dehydrogenase deficiency.

Authors :
Tenopoulou M
Chen J
Bastin J
Bennett MJ
Ischiropoulos H
Doulias PT
Source :
The Journal of biological chemistry [J Biol Chem] 2015 Apr 17; Vol. 290 (16), pp. 10486-94. Date of Electronic Publication: 2015 Mar 03.
Publication Year :
2015

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.<br /> (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Details

Language :
English
ISSN :
1083-351X
Volume :
290
Issue :
16
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
25737446
Full Text :
https://doi.org/10.1074/jbc.M114.635102