Acetylation

Acetylation - What is Acetylation?

Acetylation is a chemical reaction that is called ethanoylation in the IUPAC nomenclature. It describes a reaction that introduces an acetyl functional group into a chemical compound. The opposite chemical reaction is called deacetylation – it is the removal of the acetyl group.

The process of introducing an acetyl group results in an acetoxy group. It involves the substitution of an acetyl group for an active hydrogen atom. A reaction involving the replacement of the hydrogen atom of a hydroxyl group with an acetyl group (CH3 CO) would then yield a specific ester, the acetate.

Which proteins undergo acetylation?

Most of the proteins in the human body undergo acetylation. The process of acetylation is important for several important chemical reactions in the body. This includes:-

  • Protein formation.
  • Drug biotransformation - many drugs are processed in the body through the acetylation reaction, either by biotransformation into an effective compound or to be metabolized into substances that the body can excrete in a more simpler manner.
  • Regulation of deoxyribonucleic acid (DNA) and other genetic elements using histone acetylation. Proteins that replicate DNA and repair damaged genetic material are created directly by acetylation. Acetylation also helps in DNA transcription. Acetylation determines the energy that proteins use during duplication and this determines the accuracy of copying the genes. The erroneous zones while copying the DNA are removed by proteins and the segments are later attached. Less faulty pieces may be allowed to remain while the more flawed ones are removed. There is a way acetylation is triggered by cellular proteins. When the reaction begins, chemicals are added to the DNA-controlling proteins.
  • Reactions triggered by acetyltransferases that can lead to cancer and other diseases.

N-alpha-acetyltransferases

N-alpha-acetyltransferases help in mediating acetylation reactions. There are three common varieties of these enzymes. These are labeled A, B, and C and act within the cells to transfer molecules. They also control the proteins that build up the cellular structures.

Acetylation of Proteins

Acetylation is a vital chemical reaction that is important for co-translational and post-translational modification of proteins. Once the proteins are formed in their rudimentary forms of long polypeptide chains, they undergo several chemical reactions to form the final three dimensional structures of proteins. Acetylation is one such reaction. Some modifications include those for histones, p53, and tubulins.

Some of the important Acetylation reactions include:-

N-alpha-terminal acetylation

This is the acetylation reaction of the N-terminal alpha-amine of proteins. This is a common reaction seen in eukaryotes. Over half (40 to 50 percent) of yeast proteins and nearly all (80 to 90 percent) of human proteins are modified in this manner. This reaction has been conserved throughout evolution and has not changed much.

The reactions are mediated by N-alpha-acetyltransferases (NATs), a sub-family of the GNAT superfamily of acetyltransferases. This superfamily includes histone acetyl transferases. These NATs transfer the acetyl group from acetyl-coenzyme A to the amine group.

There are three types of N-acetyletransferases. These are labelled A, B and C. These have been extensively studied in yeast. Each subtype is specific for its substrates. These NATs are associated with the ribosome, where they acetylate the newly formed and unmodified polypeptide chain. Proteins such as actin and tropomyosin are especially dependent of NAT B acetylation to form proper actin filaments.

Humans also have the NAT A and NAT B complexes. NAT A complex activities have been associated with hypoxia-response and beta-catenin pathway that have been linked to cancer pathologies. NATA has been found to be over-expressed in papillary thyroid cancers and neuroblastomas. The human NAT B complex is associated with the cell cycle. The hNat3 subunit of the hNatB complex has been found overexpressed in some forms of cancer.

Genetic determines activities of NAT that again regulate drug metabolism. Nearly 20% of Asians have an isozyme that results in slower N-acetylation of drugs, while 50% of Whites and African-Americans do.

Lysine acetylation and deacetylation

The histone acetylation and deacetylation occurs on the lysine residues in the N-terminal tail as part of gene regulation. The mediating enzyme is often histone acetyltransferase (HAT) or histone deacetylase (HDAC). HATs and HDACs can modify the acetylation status of non-histone proteins as well.

Tubulin acetylation

Tubulin acetylation and deacetylation has been studied in Chlamydomonas. A tubulin acetyltransferase located in the axoneme. It acetylates a specific lysine residue in the α-tubulin subunit in assembled microtubule.