Lipidations

Lipidations, or lipidation, is the covalent attachment of lipid groups to biomolecules, most commonly proteins, performed by enzymes. This modification increases hydrophobicity and frequently promotes membrane association, subcellular localization, and regulation of activity.

Common lipid groups include fatty acids (myristoyl and palmitoyl), isoprenoids (farnesyl and geranylgeranyl), and glycosylphosphatidylinositol (GPI) anchors. Lipidation can attach lipids to proteins destined for the plasma membrane, organelles, or secretion pathways.

Major forms include N-myristoylation, S-palmitoylation, prenylation, and GPI-anchor addition. N-myristoylation adds a myristate to an N-terminal glycine; S-palmitoylation adds a palmitate to cysteine residues and is often reversible; prenylation attaches farnesyl or geranylgeranyl groups to a CaaX motif; GPI anchoring links proteins to a GPI lipid to create a membrane anchor.

Enzymes involved include N-myristoyltransferases (NMTs), palmitoyltransferases of the DHHC family, prenyltransferases, and GPI transamidase. Palmitoylation is the most dynamic lipidation, whereas prenylation and GPI anchoring are generally stable.

Biological significance includes directing proteins to membranes, shaping signaling pathways, and modulating interactions and stability. Dysregulated lipidation has been associated with diseases such as cancer and neurodegenerative disorders; some pathogens also rely on lipidation for host interactions.

Researchers study lipidations using mass spectrometry, metabolic labeling, and biochemical assays. Therapeutically, inhibitors of lipidation pathways (for example, farnesyltransferase inhibitors) have been explored, and statin therapy can indirectly affect prenylation by reducing isoprenoid availability.