Sirtuin family (Sirtuin-2 to Sirtuin-7) (SIRT2-7)

The sirtuin family, specifically members Sirtuin-2 through Sirtuin-7, represents a group of NAD+-dependent enzymes that regulate a wide array of cellular processes including metabolism, DNA repair, and aging (Houtkooper et al., 2012, Nature Reviews Molecular Cell Biology). Unlike the well-characterized Sirtuin-1, these "other" sirtuins are localized in various cellular compartments: Sirtuin-2 is primarily cytosolic, Sirtuin-3, Sirtuin-4, and Sirtuin-5 are mitochondrial, and Sirtuin-6 and Sirtuin-7 are nuclear (Finkel et al., 2009, Nature). They function primarily as deacylases, removing acetyl, succinyl, or malonyl groups from lysine residues on histones and metabolic enzymes, thereby altering protein function and gene expression (He et al., 2012, Cell). These proteins are implicated in various pathologies; for instance, Sirtuin-2 is a target in neurodegeneration, while Sirtuin-6 is investigated for its role in genomic stability and longevity (Kovatcheva et al., 2018, Nature Medicine). Sirtuin-3 is a key regulator of mitochondrial oxidative stress and has been linked to cardiovascular health (He et al., 2012, Cell). Sirtuin-5 and Sirtuin-4 play specialized roles in metabolic flux, particularly in the urea cycle and insulin secretion (Finkel et al., 2009, Nature). Therapeutic strategies involve both activators and inhibitors, though the high structural homology between isoforms presents a challenge for achieving high selectivity and avoiding off-target effects (Carafa et al., 2016, Clinical Epigenetics). Overall, these enzymes are critical nodes in the cellular response to nutritional and environmental stress.

Other names

Sirtuin-2Sirtuin-3Sirtuin-4Sirtuin-5Sirtuin-6Sirtuin-7Class III histone deacetylasesNAD-dependent protein deacetylases

These enzymes catalyze the NAD+-dependent deacetylation or deacylation of lysine residues on both histone and non-histone protein substrates, coupled with the cleavage of NAD+ into nicotinamide and O-acetyl-ADP-ribose (Houtkooper et al., 2012, Nature Reviews Molecular Cell Biology).