Sirtuins: Difference between revisions
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|description='''Sirtuins''' are NAD<sup>+</sup>-dependent deacetylases which play a prominent role as metabolic regulators. Their dependence on intracellular levels of NAD<sup>+</sup> (NAD<sup>+</sup> activatesย sirtuinย activity,ย whereasย NADHย inhibitsย it) makes them suitable as sensors that can detect cellular energy status. | |description='''Sirtuins''' are NAD<sup>+</sup>-dependent deacetylases which play a prominent role as metabolic regulators. Their dependence on intracellular levels of NAD<sup>+</sup> (NAD<sup>+</sup> activatesย sirtuinย activity,ย whereasย NADHย inhibitsย it) makes them suitable as sensors that can detect cellular energy status. | ||
> [[Sirtuins# | > [[Sirtuins#Sirtuin_family | '''MiPNet article''']] | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/22395773 Houtkooper_2012_Nat Rev Mol Cell Biol][http://www.ncbi.nlm.nih.gov/pubmed/14724176 Lin_2004_Genes Dev][http://www.ncbi.nlm.nih.gov/pubmed?term=Exercise%20training%20promotes%20SIRT1%20activity Ferrara_2008_Rejuvenation Res] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/22395773 Houtkooper_2012_Nat Rev Mol Cell Biol][http://www.ncbi.nlm.nih.gov/pubmed/14724176 Lin_2004_Genes Dev][http://www.ncbi.nlm.nih.gov/pubmed?term=Exercise%20training%20promotes%20SIRT1%20activity Ferrara_2008_Rejuvenation Res] | ||
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Revision as of 08:28, 19 May 2014
Description
Sirtuins are NAD+-dependent deacetylases which play a prominent role as metabolic regulators. Their dependence on intracellular levels of NAD+ (NAD+ activates sirtuin activity, whereas NADH inhibits it) makes them suitable as sensors that can detect cellular energy status. > MiPNet article
Abbreviation: Sirt
Reference: Houtkooper_2012_Nat Rev Mol Cell BiolLin_2004_Genes DevFerrara_2008_Rejuvenation Res
MitoPedia topics: Enzyme
Pesta D (2012) Sirtuin family. Mitochondr Physiol Network 2012-06-29. |
Pesta D (2012) Mitochondr Physiol Network
Abstract: A brief accout of the sirtuin family.
โข O2k-Network Lab: AT Innsbruck Gnaiger E
Labels:
Enzyme: Marker Enzyme"Marker Enzyme" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.
HRR: Theory
Sirtuin family
Characterization
Seven sirtuin orthologs (SIRT1โSIRT7) make up the ubiquitously expressed sirtuin family of enzymes as known to date. Although all sirtuins have a conserved catalytic core comprising 275 amino acids, they differ in their subcellular localization. The best characterized sirtuin, SIRT1, is mostly found in the nucleus but can shuttle to the cytosol. SIRT2 by contrast is found mainly in the cytoplasm. SIRT3, SIRT4, and SIRT5 are mainly located within the mitochondrion and SIRT6 and SIRT7 are nuclear proteins.
Activity
Sirtuins also differ according to their enzymatic activities. SIRT1 and SIRT5 exhibit deacetylase activity, SIRT4 probably acts as a mono-ADP-ribosyl transferase; SIRT2, SIRT3, and SIRT6 show both activities and the activity of SIRT7 remains still unclear although it is hypothesized that it acts as a deacetylase.
Metabolic stressors such as increased oxidative stress, intense endurance training or caloric restriction have an impact on SIRT activities, especially on SIRT1. It has been shown that activation of SIRT2 via decreased NADH levels in response to caloric restriction increases life-span in yeast.
Mechanism
Essentially, sirtuins catalyse the deacetylation of an acetylated substrate where NAD+ functions as a cosubstrate, yielding the deacetylated substrate, nicotinamide, and 2โ-O-acetyl-ADP-ribose. A relatively high Km' for NAD+ and the NAD+ dependency puts the class of enzymes at the forefront of metabolic control in the cell by linking NAD+/NADH ratios with protein deacetylation.