title: Sirtuin activation as a therapeutic approach against inborn errors of metabolism.
abstract: Protein acylation has emerged as a large family of post translational modifications in which an acyl group can alter the function of a wide variety of proteins, especially in response to metabolic stress. The acylation state is regulated through reversible acylation/deacylation. Acylation occurs enzymatically or non-enzymatically, and responds to acyl-CoA levels. Deacylation on the other hand is controlled through the NAD(+)-dependent sirtuin proteins. In several inborn errors of metabolism (IEMs), accumulation of acyl-CoAs, due to defects in amino acid and fatty acid metabolic pathways, can lead to hyperacylation of proteins. This can have a direct effect on protein function and might play a role in pathophysiology. In this review we describe several mouse and cell models for IEM that display high levels of lysine acylation. Furthermore, we discuss how sirtuins serve as a promising therapeutic target to restore acylation state and could treat IEMs. In this context we examine several pharmacological sirtuin activators, such as resveratrol, NAD(+) precursors and PARP and CD38 inhibitors.
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
authors.forename: Jeannette C
authors.initials: JC
authors.lastname: Bleeker
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. r.h.houtkooper@amc.uva.nl.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000215:Acylation; D000818:Animals; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000628:therapy*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D037761:Sirtuins