title: Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism.
abstract: Inherited disorders of acyl-CoA metabolism, such as defects in amino acid metabolism and fatty acid oxidation can present with severe clinical symptoms either neonatally or later in life, but the pathophysiological mechanisms are often incompletely understood. We now report the discovery of a novel biochemical mechanism that could contribute to the pathophysiology of these disorders. We identified increased protein lysine butyrylation in short-chain acyl-CoA dehydrogenase (SCAD) deficient mice as a result of the accumulation of butyryl-CoA. Similarly, in SCAD deficient fibroblasts, lysine butyrylation was increased. Furthermore, malonyl-CoA decarboxylase (MCD) deficient patient cells had increased levels of malonylated lysines and propionyl-CoA carboxylase (PCC) deficient patient cells had increased propionylation of lysines. Since lysine acylation can greatly impact protein function, aberrant lysine acylation in inherited disorders associated with acyl-CoA accumulation may well play a role in their disease pathophysiology.
authors: Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: Olga
authors: O
authors: Pougovkina
authors: Heleen
authors: H
authors: Te Brinke
authors: Ronald J A
authors: RJ
authors: Wanders
authors: Sander M
authors: SM
authors: Houten
authors: Vincent C J
authors: VC
authors: de Boer
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D000215:Acylation / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D005227:Fatty Acids; D011506:Proteins; D042964:Acyl-CoA Dehydrogenase; D008239:Lysine