deacetylation

Deacetylation is a chemical reaction in which an acetyl group is removed from a molecule. The process can occur spontaneously under certain conditions or be catalyzed by enzymes. Deacetylation can involve removal of acetyl groups from nitrogen, oxygen, or other atoms, altering the molecule’s charge, polarity, and reactivity.

In biology, deacetylation most often refers to removal of acetyl groups from lysine residues in proteins or from histone proteins. The major enzyme families are histone deacetylases (HDACs) and sirtuins (SIRTs). HDACs are typically zinc-dependent hydrolases that cleave acetyl-lysine bonds, releasing acetate and restoring a positive charge on lysine. Sirtuins are NAD+-dependent deacetylases that use a different reaction mechanism. Deacetylases also target a wide range of non-histone proteins, influencing gene expression, metabolism, signaling, and protein function.

Biological significance includes chromatin remodeling and transcriptional regulation, since histone deacetylation leads to chromatin condensation and gene silencing. Deacetylation of metabolic enzymes or transcription factors can modify activity, stability, or cellular localization. The acetylation–deacetylation balance is controlled by acetyltransferases and deacetylases and responds to cellular signals, metabolic state, and environmental cues.

Applications and relevance extend to medicine and chemistry. HDAC inhibitors are used as anticancer agents and are investigated for neurodegenerative and metabolic diseases. In chemical synthesis, deacetylation is routinely used to remove acetyl protecting groups, unveiling free amines or alcohols for further reactions. Laboratory methods for studying deacetylation include HDAC activity assays and mass spectrometry or antibody-based detection of acetylation.