depalmitoylated

Depalmitoylated describes a molecule that has lost its palmitoyl group, most commonly referring to proteins that have undergone depalmitoylation—the enzymatic removal of the palmitoyl fatty acid from a cysteine or sometimes other residues.

Palmitoylation is a reversible post-translational modification in which a 16-carbon saturated fatty acid, palmitate, is attached to proteins via a thioester bond to cysteine residues (S-palmitoylation). Depalmitoylation hydrolyzes this bond, releasing palmitate and restoring the free thiol; this process can regulate protein localization, stability, and interactions.

Enzymes known to mediate depalmitoylation include acyl-protein thioesterases (APTs such as APT1/LYPLA1 and APT2/LYPLA2) and lysosomal palmitoyl-protein thioesterases (PPT1 and PPT2). Other serine hydrolases in various enzyme families, including members of the ABHD group, have also been implicated in removing palmitoyl groups from select substrates. The activity often depends on cellular compartment and substrate specificity.

Depalmitoylation contributes to dynamic cycles that control membrane association and trafficking of signaling proteins, receptors, and enzymes. In neurons, rapid depalmitoylation reshapes synaptic protein localization and signaling; in other tissues, it can influence cell growth, migration, and metabolism. Dysregulation of depalmitoylation has been linked to neurological disorders and cancer, and certain depalmitoylating enzymes are investigated as therapeutic targets.

Detection and study of depalmitoylation employ methods such as acyl-biotin exchange (ABE), acyl-resin-assisted capture (Acyl-RAC), and metabolic labeling with palmitate analogs followed by click chemistry, combined with mass spectrometry or imaging.