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Sirtuin activation as a therapeutic approach against inborn errors of metabolism
Author(s) -
Bleeker Jeannette C.,
Houtkooper Riekelt H.
Publication year - 2016
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-016-9939-8
Subject(s) - sirtuin , acylation , nad+ kinase , biochemistry , lysine , chemistry , context (archaeology) , biology , amino acid , enzyme , paleontology , catalysis
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.