page_title: N-acetyltransferase
section_title: Enzyme Mechanism
hierarchical_section_title: N-acetyltransferase / Enzyme Mechanism
caption_attribution_description: English: The mechanism of N-acetyltransferase within the catalytic triad of Asp, His, and Cys.
context_page_description: N-acetyltransferase is an enzyme that catalyzes the transfer of acetyl groups from acetyl-CoA to arylamines, arylhydroxylamines and arylhydrazines. They have wide specificity for aromatic amines, particularly serotonin, and can also catalyze acetyl transfer between arylamines without CoA. N-acetyltransferases are cytosolic enzymes found in the liver and many tissues of most mammalian species, except the dog and fox, which cannot acetylate xenobiotics.Acetyl groups are important in the conjugation of metabolites from the liver, to allow excretion of the byproducts. This is especially important in the metabolism and excretion of drug products.
context_section_description: NAT enzymes are differentiated by the presence of a conserved catalytic triad that favors aromatic amine and hydrazine substrates. NATs catalyze the acetylation of small molecules through a double displacement reaction called the ping pong bi bi reaction. The mechanism consists of two sequential reactions. In reaction one acetyl-CoA initially binds to the enzyme and acetylates Cys⁶⁸. In reaction two, after acetyl-CoA is released, the acetyl acceptor interacts with the acetylated enzyme to form product. This second reaction is independent of the acetyl donor since it leaves the enzyme before the acetyl acceptor binds. However, like with many ping pong bi bi reactions, its possible there is competition between the acetyl donor and acetyl acceptor for the unacetylated enzyme. This leads to substrate-dependent inhibition at high concentrations.
caption: Depiction of the N-acetyltransfersase enzyme mechanism.[7]
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