Enzymatic activity of the SIRTs. NAD+ is a substrate for all SIRTs in reaction of nicotinamide (NAM) production. In the deacylation reaction, NAD+ receives the acetyl (Ac) group from the protein. The adenine dinucleotide moiety from NAD+ is linked to various residues on the target protein in ADP-ribosyl transfer. SIRT1, 2, 3, 5 and 7 show the lysine deacetylation activity of target proteins in which the NAD+ coenzyme is used to produce NAM and 2′-O-acetyl-ADP-ribose (2′-OAADPr). SIRT4 exhibits only ADP-ribosyl transferase activity, and NAD+ is used as a donor of the ADP-ribose group for target proteins. ADP-ribosyl transferase activity shares with SIRT6. SIRT5 uses NAD+ as a cofactor in the demalonylation and desuccinylation of target proteins, generating NAM and 2’-O-malonyl-ADP-ribose (2′-OMADPr) and 2′-O-succinyl-ADP-ribose (2′-OSADPr), respectively. Modification based on Morigi et al. [4,5].