Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism.

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Pougovkina O et al. Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism. J Inherit Metab Dis. 2014 Feb 15. [Epub ahead of print]

 

An elegant study that formulates a new hypothesis for the role of aberrant acyl-CoA accumulation in disorders of acyl-CoA metabolism.

Lysine acylation (in particular, acetylation) has previously been found to be an important post-translational regulatory mechanism both inside the nucleus (e.g. histone acetylation) and outside the nucleus, particularly in mitochondria. Although lysine acetylation has been the most closely studied, other forms of lysine acylation have also been observed.

In this study, the authors note increased lysine acylation in cells affected with disorders of acyl-CoA metabolism, the type of aberrant acylation corresponding to the abnormally accumulating acyl-CoA species: increased lysine butyrylation in the livers of SCAD-deficient mice and in the fibroblasts of human patients with SCAD deficiency;  and increased lysine propionylation and malonylation in the fibroblasts of patients with propionyl-CoA carboxylase and malonyl-CoA decarboxylase, respectively.

This observation provides a starting point for the elucidation of a possible pathophysiological mechanism in disorders of acyl-CoA metabolism, whereby the toxicity of accumulating acyl-CoA species could be mediated by excessive protein acylation.

Posted by Alina Levtova, MD.

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