|All about Sirtuin!
What is Sirtuin?
Sirtuin is a gene and is made up of a class of proteins that are found in
organisms ranging from bacteria to humans with either histone deacetylase or
mono-ribosyltransferase activity. It is also known as Silent Information
Regulator Two (Sir2 or SIRT) proteins and is named after yeast silent
mating-type information regulation two. Yeast Sir2 and some Sirtuins are made up
of protein deacetylases which are enzymes that act as the one that removes
acetyl groups from lysine amino acids in proteins.
So how many Sirtuins are there? Based on the Northern/Verdin diagram, there
are a total of seven SIRT which is classified in four groups.
Class 1 consists of SIRT1, SIRT2, and SIRT3. SIRT1 gene, located in the
nucleus which made up of NAD-dependent deacetylase Sirtuin 1, has an enzyme that
deacetylates proteins which contribute to cellular regulation. This is also
termed as a reaction to the stressors and/or longevity. Such activity is being
regulated within the cells that have high insulin resistance. Then, it induces
its expression in order to be able to increase insulin sensitivity by which the
associated molecule is believed to have the ability to improve insulin
sensitivity. SIRT2 gene, located within the cytoplasm, is further made up of
NAD-dependent deacetylase Sirtuin 2. It has an enzyme called tubulin deacetylase,
which works by blocking the entry to chromosome condensation as a reaction to
mitotic stress. This is how Sirtuin does its function as a part of normal cell
SIRT3 gene, located in the nucleus and is also made up of NAD-dependent
deacetylase Sirtuin 3. This gene has two primary functions which are
predominantly mitochondrial in nature. It implicates the regulation of metabolic
processes within the body. Furthermore, it also has a nuclear function as it
protects cardiomyocytes from stress-mediated cellular damage due to
deacetylation of a nuclear factor.
Class II consists of SIRT4 gene is located in the mitochondria of
intracellular molecules. It is made up of silent mating type information
regulation-2 homolog-4. It also acts in beta cell mitochondria in order to
repress the activity of glutamate dehydrogenase by means of the ribosylation
process of adenosine tryphosphate. As a result, the insulin secretion in
response to the presence of certain amino acids is regulated.
Class III consists of SIRT5 gene, located in the mitochondria of
intracellular molecules, is further made up of NAD-dependent deacetylase
sirtuin-5. It functions as an intracellular regulatory protein that has a
mono-ADP-ribosyltransferase activity. It also takes part in natural bodily
processes that involve ammonia detoxification.
Class IV consists of SIRT6 and SIRT7. SIRT6 gene, located in the nucleus of
intracellular molecules, is comprised of NAD-dependent deacetylase Sirtuin 6. It
regulates glucose homeostasis, DNA and also certain processes involved in
metabolism. SIRT7 gene, located in the nucleolus of intracellular molecules,
consists of NAD-dependent deacetylase sirtuin-7. Its main function is in rDNA
transcription. It has other functions as well, such as in increasing stress
resistance of the body’s cardiomyocytes as well as preventing apoptosis from
happening. In mice, this particular gene has been tested to have the ability to
prevent inflammatory cardiomyopathy.
In addition, studies today show that Resveratrol can trigger Sirtuin genes to
be able to cause an extension of the regular life span. In fact, something likes
this is quite the same with the effect of calorie restriction.
According to Dr. Jef Boeke, Sirtuins are highly conserved across various
species; hence it is a never-before-described gene. It also has clinical
significance, such as in treating degenerative diseases like Type II diabetes
mellitus, artherosclerosis, and gout, due to the nicotinamide-binding effect of
increased Sirtuin activity. Basically, Sirtuins are very important when it comes
to normal bodily functions such as metabolism, regulation of insulin secretion,
cell cycle tumorigenesis, rDNA transcription, DNA repair, and ammonia
detoxification, among others.