Acetylation Chemical Reaction Explained


It is a chemical reaction that is conducted usually with acetic acid that releases acetyl free radical (CH3CO) which substitutes active hydrogen of an hydroxyl group and creates acetylatic organic compound. It is one of the synthetic bio transformations which operate in the metabolism of drugs where metabolites are more readily excreted than the parent drug. In these processes acetic anhydride is commonly used as an agent of acetylation because it reacts with free hydroxyl group(it is used in the synthesis of aspirin and heroin).Acetylation is one of the principal metabolic pathways of creating of sulfonamides.
From all the other mammals dogs are the only ones amongst them that in their tissues acetylation doesn't occures.
In biology, i.e., in living cells, acetylation occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, and tubulins.




 N-alpha-terminal Acetylation
Acetylation of the N-terminal alpha-amine of proteins is a widespread modification in eukaryotes. Forty to fifty percent of yeast proteins, and 80-90% of human proteins are modified in this manner, and the pattern of modification is found to be conserved throughout evolution. The modification is performed by N-alpha-acetyltransferases (NATs), a sub-family of the GNAT superfamily of acetyltransferases, which also include histone acetyl transferases. The GNATs transfer the acetylgroup from acetyl-coenzyme A to the amine group. The NATs have been most extensively studied in yeast. Here, three NAT complexes, NatA/B/C, have been found to perform most N-alpha-terminal acetylations. They have sequence specificity for their substrates, and it is believed that they are associated with the ribosome, where they acetyla In humans, the human NatA and NatB complexes have been identified and characterized. Subunits of the human NatA complex have been coupled to cancer-related processes such as hypoxia-response and the beta-catenin pathway. It has been found to be over-expressed in papillary thyroid carcinoma and neuroblastoma. The human NatB complex have been coupled to cell cycle. The hNat3 subunit of the hNatB complex have been found overexpressed in some forms of cancer.

Despite being such a conserved and widespread modification, little is known about the biological role of N-alpha-terminal acetylation. Proteins such as actin and tropomyosin have been found to be dependent of NatB acetylation to form proper actin filaments. Yet this is only an example of the potential importance of this modification.

 Lysine Acetylation and Deacetylation

In histone acetylation and deacetylation, the histones are acetylated and deacetylated on lysine residues in the N-terminal tail as part of gene regulation. Typically, these reactions are catalyzed by enzymes with "histone acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity, although it should be noted that HATs and HDACs can modify the acetylation status of non-histone proteins as well.

The regulation of transcription factors, molecular chaperones, effector proteins, and cytoskeletal proteins by acetylation/deacetylation is rising as a significant post-translational mechanism of regulation,that is analogue to phosphorylation by the action of kinases or dephosphorylated by the action of phosphatases. Not only can the acetylation state of a protein modify its activity, there have appeared recently suggestions that this post-translational modification might crosstalk with phosphorylation, ubiquitination, methylation,sumoylation, and others for dynamic control of cellular signaling.

The tubulin system is the best shown in Chlamydomonas. A tubulin acetyltransferase that is found in the axoneme acetylates a specific lysine residue in the α-tubulin subunit in assembled microtubule. Once when it gets disassembled, this acetylation removes by another specific deacetylase and that is named cytosolic.Observing this the axonemal microtubules (long half-life) carry this signature acetylation that is missing from cytosolic microtubules (short half-life).

Resources

Reversible Protein Acetylation (Novartis Foundation Symposia)
Histone Deacetylases: Transcriptional Regulation and Other Cellular Functions (Cancer Drug Discovery and Development)
The Histone Code and Beyond: New Approaches to Cancer Therapy (Ernst Schering Foundation Symposium Proceedings)
Chromatin and Disease (Subcellular Biochemistry)
Protein Complexes that Modify Chromatin. Current Topics in Microbiology and Immunology, No. 274
Chromatin Dynamics in Cellular Function (Results and Problems in Cell Differentiation)
Epigenetics in Biology and Medicine