palmitoylenzyme

Palmitoylenzyme is not a single enzyme, but a term often used to describe enzymes that catalyze the palmitoylation or depalmitoylation of proteins. Palmitoylation is a reversible post-translational modification in which a 16-carbon palmitoyl group is covalently attached to a cysteine residue via a thioester bond, influencing membrane association, subcellular localization, trafficking, and protein interactions.

Palmitoyltransferases: The DHHC family are the main enzymes that catalyze palmitoylation. They are integral membrane proteins with a catalytic DHHC motif in the cytosolic region and use palmitoyl-CoA as the donor. Substrate proteins include small GTPases such as Ras, signaling receptors, and several synaptic proteins. Palmitoylation by these enzymes is often dynamic and regulated by cellular context and by depalmitoylases that remove the modification.

Depalmitoylases: Enzymes that remove palmitoyl groups include acyl-protein thioesterases APT1 (LYPLA1) and APT2 (LYPLA2), as well as PPT1 and PPT2 in lysosomes, and some ABHD family members. These depalmitoylases reverse palmitoylation, modulating the activity, localization, and stability of substrate proteins. The balance between palmitoylation and depalmitoylation determines the signaling state of many proteins.

Biological significance and clinical aspects: Reversible palmitoylation regulates key signaling pathways, neuronal development, and vesicular trafficking. Dysregulation of palmitoyl enzymes has been linked to diseases including cancer and neurodegenerative disorders. For example, altered DHHC function can impact Ras signaling, and PPT1 deficiency causes the neurodegenerative disorder CLN1. Ongoing research seeks to map substrate networks and explore therapeutic modulation of palmitoylation dynamics.