Sirtuins are a family of signaling proteins involved in metabolic regulation.[2][3] They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life.[2] Chemically, sirtuins are a class of proteins that possess either mono-ADP-ribosyltransferase or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity.[4][5][6] The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2',[7] the gene responsible for cellular regulation in yeast.
From in vitro studies, sirtuins were thought to be implicated in influencing cellular processes like aging, transcription, apoptosis, inflammation[8] and stress resistance, as well as energy efficiency and alertness during low-calorie situations.[9] As of 2018, there was no clinical evidence that sirtuins affect human aging,[10] and a 2022 review criticized researchers who propagate this claim.[11]
Yeast Sir2 and some, but not all, sirtuins are protein deacetylases. Unlike other known protein deacetylases, which simply hydrolyze acetyl-lysine residues, the sirtuin-mediated deacetylation reaction couples lysine deacetylation to NAD+ hydrolysis.[12] This hydrolysis yields O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, which is an inhibitor of sirtuin activity itself. These proteins utilize NAD+ to maintain cellular health and turn NAD+ to nicotinamide (NAM).[13] The dependence of sirtuins on NAD+ links their enzymatic activity directly to the energy status of the cell via the cellular NAD+:NADH ratio, the absolute levels of NAD+, NADH or NAM or a combination of these variables.
Sirtuins that deacetylate histones are structurally and mechanistically distinct from other classes of histone deacetylases (classes I, IIA, IIB and IV), which have a different protein fold and use Zn2+ as a cofactor.[14][15]
^PDB: 1szd; Zhao K, Harshaw R, Chai X, Marmorstein R (June 2004). "Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases". Proceedings of the National Academy of Sciences of the United States of America. 101 (23): 8563–8. Bibcode:2004PNAS..101.8563Z. doi:10.1073/pnas.0401057101. PMC 423234. PMID 15150415.
^ abYe X, Li M, Hou T, Gao T, Zhu WG, Yang Y (3 January 2017). "Sirtuins in glucose and lipid metabolism". Oncotarget (Review). 8 (1): 1845–1859. doi:10.18632/oncotarget.12157. PMC 5352102. PMID 27659520.
^Yamamoto H, Schoonjans K, Auwerx J (August 2007). "Sirtuin functions in health and disease". Molecular Endocrinology. 21 (8): 1745–55. doi:10.1210/me.2007-0079. PMID 17456799.
^Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin H (November 2011). "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase". Science. 334 (6057): 806–9. Bibcode:2011Sci...334..806D. doi:10.1126/science.1207861. PMC 3217313. PMID 22076378.
^Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H (April 2013). "SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine". Nature. 496 (7443): 110–3. Bibcode:2013Natur.496..110J. doi:10.1038/nature12038. PMC 3635073. PMID 23552949.
^Rack JG, Morra R, Barkauskaite E, Kraehenbuehl R, Ariza A, Qu Y, Ortmayer M, Leidecker O, Cameron DR, Matic I, Peleg AY, Leys D, Traven A, Ahel I (July 2015). "Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens". Molecular Cell. 59 (2): 309–20. doi:10.1016/j.molcel.2015.06.013. PMC 4518038. PMID 26166706.
^EntrezGene 23410
^Preyat N, Leo O (May 2013). "Sirtuin deacylases: a molecular link between metabolism and immunity". Journal of Leukocyte Biology. 93 (5): 669–80. doi:10.1189/jlb.1112557. PMID 23325925. S2CID 3070941.
^Satoh A, Brace CS, Ben-Josef G, West T, Wozniak DF, Holtzman DM, Herzog ED, Imai S (July 2010). "SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus". The Journal of Neuroscience. 30 (30): 10220–32. doi:10.1523/JNEUROSCI.1385-10.2010. PMC 2922851. PMID 20668205.
^Brenner C (2022-09-22). "Sirtuins are not conserved longevity genes". Life Metabolism. 1 (2): 122–133. doi:10.1093/lifemeta/loac025. ISSN 2755-0230. PMC 10081735.
^Klein MA, Denu JM (2020). "Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators". Journal of Biological Chemistry. 295 (32): 11021–11041. doi:10.1074/jbc.REV120.011438. PMC 7415977. PMID 32518153.
^"NMN vs NR: The Differences Between These 2 NAD+ Precursors". www.nmn.com. Retrieved 2021-01-04.
^Bürger M, Chory J (2018). "Structural and chemical biology of deacetylases for carbohydrates, proteins, small molecules and histones". Communications Biology. 1: 217. doi:10.1038/s42003-018-0214-4. PMC 6281622. PMID 30534609.
^Marks PA, Xu WS (July 2009). "Histone deacetylase inhibitors: Potential in cancer therapy". Journal of Cellular Biochemistry. 107 (4): 600–8. doi:10.1002/jcb.22185. PMC 2766855. PMID 19459166.
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved...
Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent...
NAD-dependent deacetylase sirtuin 2 is an enzyme that in humans is encoded by the SIRT2 gene. SIRT2 is an NAD+ (nicotinamide adenine dinucleotide)-dependent...
NAD-dependent deacetylase sirtuin-3, mitochondrial also known as SIRT3 is a protein that in humans is encoded by the SIRT3 gene [sirtuin (silent mating type...
Sirtuin 6 (SIRT6 or Sirt6) is a stress responsive protein deacetylase and mono-ADP ribosyltransferase enzyme encoded by the SIRT6 gene. In laboratory...
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NAD-dependent deacetylase sirtuin 7 is an enzyme that in humans is encoded by the SIRT7 gene. SIRT7 is member of the mammalian sirtuin family of proteins, which...
Sirtuin (silent mating type information regulation 2 homolog) 5 (S. cerevisiae), also known as SIRT5 is a protein which in humans in encoded by the SIRT5...
Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene. SIRT4 is member of the mammalian sirtuin family...
However, non-histone proteins can be deacetylated by sirtuins as well. These activities of sirtuins are particularly interesting because of their importance...
seeds and skin.[citation needed] Cyanidin has been found to be a potent sirtuin 6 (SIRT6) activator. Antirrhinin (cyanidin-3-rutinoside or 3-C-R), found...
several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression. Figure 4: Epigenetic basis...
Preliminary research indicates that sirtuins are activated by fasting and serve as "energy sensors" during metabolism. Sirtuins, specifically Sir2 (found in...
several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression. Figure 4: Epigenetic basis...
several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression. Figure 4: Epigenetic basis...
level of stimulation can vary between individual fruits. Fisetin is a sirtuin-activating compound and has been shown in laboratory studies to extend...
cobblestone phenotype when lining vessel walls. Inhibition of the sirtuin protein sirtuin 1 (SIRT1) in HUVECs has been shown to induce cellular senescence...
phosphate synthetase I (CPS I), interacts with a class of molecules called sirtuins, NAD dependent protein deacetylases, and ATP to form carbamoyl phosphate...
ageing-controlling pathway in evolution and among its targets are the FOXO3/Sirtuin transcription factors and the mTOR complexes, probably responsive to caloric...
and -10 are related to yeast Hda1 gene; Class III, also known as the sirtuins are related to the Sir2 gene and include SIRT1-7 Class IV, which contains...
blocks are released from the vesicle through the action of permeases. Sirtuin 1 (SIRT1) stimulates autophagy by preventing acetylation of proteins (via...
to the sirtuin family, a broadly conserved family of NAD+-dependent protein deacetylases. CobB is a bacterial protein that belongs to the sirtuin family...
endproducts inhibitory effects. It is also a sirtuin-activating compound, a chemical compound having an effect on sirtuins, a group of enzymes that use NAD+ to...