Question

The sirtuins are a class of NAD-dependent deacetylases that are thought to play a role in the cellular response to nutritional status. Some sirtuins are involved in remodeling chromatin structure. A) How would you expect deacetylation of histones to affect the transcriptional activity of genes? B) Sirtuin 3 (Sirt3) deacetylates a specific lysine in the active site of acetyl-CoA synthetase, activating the enzyme. Why would this particular deacetylation reflect nutritional status? Remember, acetyl-CoA synthetase catalyzes the reaction: ATP + acetate + CoA <=> AMP + PPi + acetyl-CoA

Answer 1

Ans. The process of acetylation involves the relaxation of chromatin by removing positive charge from the histones which allows the fast and easy transcription of the genes. On the contrary the deacetylation means the removal of acetyl group from the histones means removal of negative charge and more positive charge that allow the greater interaction of the N termini of histones with the negatively charged phosphate groups of DNA. This makes more stable structure and hinders the transcription process. This is why the deacetylation makes the transcription process slower and sometimes inhibited.

b. The deacetylation of Sirtuin 3 reflects the nutrition status because it helps in maintaining the basal ATP levels and act as mitochondrial electron transport regulator. The deacetylation of Sirtuin 3 enhance the LCAD activity and increased fatty acid oxidation. In this way it increases the ATP production and shows a better nutritional condition.