Difference between revisions of "Sirtuins"
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Seven sirtuin orthologs which make up the ubiquitously expressed sirtuin family of enzymes are known to date (SIRT1–SIRT7). 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. | Seven sirtuin orthologs which make up the ubiquitously expressed sirtuin family of enzymes are known to date (SIRT1–SIRT7). 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. | ||
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. | 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. | ||
Essentially, sirtuins catalyse the deacetylation of an acetylated substrate where NAD+ functions as a cosubstrate, yielding the deacetylated substrate, nicotinamide, and 2’-O-acetyl-ADP-ribose. A relatively high | '''Mechanism''' | ||
Essentially, sirtuins catalyse the deacetylation of an acetylated substrate where NAD+ functions as a cosubstrate, yielding the deacetylated substrate, nicotinamide, and 2’-O-acetyl-ADP-ribose. A relatively high ''K''m 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. | |||
Revision as of 02:56, 29 June 2012
- high-resolution terminology - matching measurements at high-resolution
Sirtuins
Description
Sirtuins are NAD+-dependent deacetylases which play a prominent role as metabolic regulators. Their dependence on intracellular levels of NAD+ or NAD in its reduced form NADH makes them suitable as sensors that can detect cellular energy status.
Abbreviation: Sirt
Reference: Houtkooper_2012_Nat Rev Mol Cell Biol
MitoPedia topics: Enzyme
Seven sirtuin orthologs which make up the ubiquitously expressed sirtuin family of enzymes are known to date (SIRT1–SIRT7). 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.
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.
Mechanism
Essentially, sirtuins catalyse the deacetylation of an acetylated substrate where NAD+ functions as a cosubstrate, yielding the deacetylated substrate, nicotinamide, and 2’-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.
