Sirtuin

Sirtuins, Sir2 also like proteins are a family of multifunctional enzymes from the group of histone deacetylases (HDAC, EC 3.5.1.98 ). They come highly evolutionarily conserved in all living organisms, such as viruses, bacteria, yeast, worms, insects, mammals and humans. While most simple organisms - like bacteria - only one or a few sirtuins possess four yeasts and humans have seven of these enzymes.

The name is derived from the gene Sirtuin Sir2 (silent mating type information regulation 2) from yeast, which is responsible for cellular regulation.

The histone deacetylases class III interact with acetylated lysine residues in protein substrates such as histones and deacetylate this a NAD - dependent mechanism. A second catalytic mechanism has been described, the ADP -ribosylation ( EC 2.4.2.31 ) - Furthermore, for human sirtuins - with the exception of SIRT4. This is made responsible for the regulation of aging processes, transcription, apoptosis, and stress resistance.

Sirtuin - types

Sirtuins are classified according to their amino acid sequence. The following sirtuins are known:

Human sirtuin substrates

Deacetylation of classical substrates of sirtuins, lysine termini of histones, leads to such a change in the basicity of nitrogen in the lysine residue. With a free amine at the end of protruding from the histone nitrogen termini wound about the condensed DNA more strongly to the protein complex so that the transcription is disrupted or prevented by other enzymes. This results in a gene - silencing of the corresponding gene segment, which manifests itself in a reduced expression of the encoded in this locus enzymes. Another important substrates, their activity can be modulated by deacetylation or ADP -ribosylation are shown in the table:

Importance

Because of their ability to modify numerous enzymes and proteins that play a key role in various diseases, sirtuins have moved in recent years more and more into the focus of research. Especially the fact that numerous target proteins play a role in pathological mechanisms of abnormal cells ( cancer) raises the hope of new treatment options for certain cancers. Also, enzymes, diabetes mellitus and obesity play a role in Alzheimer 's disease, Parkinson's disease, are among the substrates of sirtuins. Their effect on the cellular aging would provide a better understanding of aging in human cells.

Critical review

Sirtuins are repeatedly referred due to their life-prolonging effect on microorganisms in the press as " anti-aging enzymes ". These effects of increased Sirt1 activity was shown in experiments with yeast and the results are confirmed in other model organisms through experiments with the sirtuin activator resveratrol. However, these studies can not be easily transmitted to humans, since the extension of the life of the microorganisms essentially on a calorie restriction is based. Experiments on mice showed no prolongation of life, but age-related degenerative diseases could be significantly delayed ..