Lands’ cycle enzymes for phosphatidylcholine remodeling (LPCATs/PLA2s)

The Lands' cycle enzymes for phosphatidylcholine remodeling are a group of enzymes, primarily phospholipases A2 (PLA2) and lysophosphatidylcholine acyltransferases (LPCATs), that regulate the deacylation-reacylation process of phospholipids (1.2.1, 1.3.2). This cycle is essential for maintaining the specific fatty acid composition of cell membranes, particularly the enrichment of polyunsaturated fatty acids at the sn-2 position of phosphatidylcholine (1.4.2). In humans, the cycle involves four LPCAT isoforms (LPCAT1-4) with distinct roles: LPCAT1 is vital for lung surfactant production, while LPCAT2 and LPCAT3 are involved in inflammatory signaling and metabolic regulation (1.1.1, 1.1.3, 1.1.4). Dysregulation of these enzymes is associated with various pathologies, including cancer, where upregulated LPCATs support rapid membrane synthesis and tumor growth (1.1.1, 1.3.2). They also play roles in atherosclerosis, neonatal respiratory distress syndrome, and neurodegenerative diseases like Alzheimer's (1.1.3, 1.2.1, 1.5.2). Pharmacological modulation of the Lands' cycle, such as through LPCAT1 inhibitors like quinacrine or LPCAT2 inhibitors like TSI-01, is being explored as a strategy to treat cancer and inflammation (1.1.2, 1.1.4). However, therapeutic intervention must be carefully managed to avoid adverse effects on essential functions like pulmonary surfactant homeostasis (1.1.2).

Other names

Phospholipid remodeling enzymesDeacylation-reacylation cycle enzymesLysophosphatidylcholine acyltransferasesLPCATsPhospholipases A2PLA2sLPLATsMBOATs

Inhibition of lysophosphatidylcholine acyltransferase (LPCAT) activity to disrupt membrane remodeling and lipid mediator production; inhibition of phospholipase A2 (PLA2) to prevent deacylation of phospholipids and release of fatty acid precursors.