Figure 3

The enzymatic activity of sirtuins. (a) The components necessary for sirtuin-mediated deacetylase activity are the sirtuin, β-NAD, and the N-acetylated substrate. (b) The components form a tertiary complex and, during the enzymatic reaction, the nicotinamide is expelled from bound NAD to generate an oxocarbonium-like transition state in which the carbonyl oxygen of the acetyl group attacks the C1 carbon of ADP. After alkylamidate and cyclic intermediates and possibly protonation of the amine leaving group (not shown), the products (c) are formed: the deacetylated protein, 2'-O-acetyl-ADP-ribose, and nicotinamide. The 2'-O-acetyl-ADP-ribose is released into solution, where it equilibrates with 3'-O-acetyl-ADP-ribose. Adapted with modifications from [78].