NAD-dependent protein deacetylase sirtuin (SIRT)

Sirtuins are a family of seven NAD+-dependent enzymes (SIRT1–SIRT7) that function primarily as protein deacetylases, though some also exhibit ADP-ribosyltransferase, desuccinylase, and demalonylase activities (UniProt, 2023). These enzymes act as metabolic sensors by linking cellular energy status, specifically the NAD+/NADH ratio, to the regulation of gene expression and protein function (PubMed: 31434153). Sirtuins are localized across various cellular compartments—SIRT1, SIRT6, and SIRT7 are primarily nuclear; SIRT2 is cytoplasmic; and SIRT3, SIRT4, and SIRT5 are mitochondrial (NIH, 2022). They play pivotal roles in DNA repair, apoptosis, circadian rhythms, and mitochondrial biogenesis, making them central players in the biology of aging and longevity (PubMed: 23915102). In disease contexts, sirtuin dysregulation is linked to metabolic disorders like type 2 diabetes, neurodegenerative conditions such as Alzheimer’s disease, and various forms of cancer (StatPearls, 2023). Therapeutic strategies involve sirtuin-activating compounds (STACs) to treat metabolic and age-related diseases, while sirtuin inhibitors are being explored for specific oncological applications (PubChem, 2024).

Other names

Silent information regulatorSIR2-like proteinClass III histone deacetylaseNAD-dependent protein deacetylaseHDAC Class III

Sirtuins catalyze the deacetylation of target proteins by coupling the hydrolysis of nicotinamide adenine dinucleotide (NAD+) to the cleavage of the acetyl group from lysine residues, producing nicotinamide and O-acetyl-ADP-ribose. This activity regulates the function of histones and non-histone proteins involved in transcription, metabolism, and cellular survival.