Nacetylation

N-acetylation is the enzymatic transfer of an acetyl group from acetyl-CoA to a nitrogen atom in a substrate. In biology, it most often refers to modification of proteins, though it also occurs on small molecules. In proteins, N-acetylation can take place at the N-terminus (N-terminal acetylation) or on the side chain of lysine residues (Nε-acetylation). The reaction is catalyzed by a family of enzymes known as N-acetyltransferases (NATs), including several eukaryotic Nat enzymes that act co-translationally as proteins emerge from the ribosome. Substrate specificity is largely determined by the sequence or context around the target nitrogen.

N-terminal acetylation is very common in eukaryotes and can influence a protein’s stability, localization, interactions, and folding. It can also affect degradation via the N-end rule pathway in certain contexts, functioning as part of a degradation signal. Lysine Nε-acetylation is a major post-translational modification that modulates chromatin structure and gene expression, as well as other cellular processes; this form is typically associated with histone acetyltransferases and other acetyltransferases.

In pharmacology and toxicology, N-acetylation also describes a Phase II metabolic step that adds an acetyl group to various amines, catalyzed in humans by NAT1 and NAT2. Genetic polymorphisms in these enzymes yield fast and slow acetylator phenotypes, influencing drug response and cancer risk. Detection and study of N-acetylation employ methods such as mass spectrometry and specific enzymatic assays.