The sirtuins represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs) and have been shown to catalyze a reaction that couples lysine deacetylation to the formation of nicotinamide and O-acetyl-ADP-ribose from NAD+ and the abstracted acetyl group. SIRT7 is a member of this family of proteins and is present in prokaryotes and eukaryotes. All SIR2-like proteins have a sirtuin core domain, which contains a series of sequence motifs conserved in organisms ranging from bacteria to humans. Bacterial, yeast, and mammalian sirtuins are able to metabolize NAD+ and several act as mono-ADP-ribosyltransferases. The enzymatic function of sirtuins is not yet completely understood but as mentioned above, recent reports of histone-activated SIR2-mediated NAD+ metabolism and NAD+-activated SIR2-mediated histone deacetylation sμggest a possible coupled reciprocal activation mechanism involving interactions of SIR2 with NAD+ and the N-ε-acetyl-lysine groups of acetylated histone.