Abstract
Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.
Highlights
General Features of Lysophosphatidylcholine Lysophosphatidylcholine (LPC), called lysolecithins, is a class of lipid biomolecule derived by the cleaving of phosphatidylcholine (PC) via the action of phospholipase A2 (PLA2) [1,2] and/or by the transfer of fatty acids to free cholesterol via lecithin-cholesterol acyltransferase (LCAT) [3]
LPCs can be produced in the circulation when PLA2 cleaves PCs, they can be converted back to PCs by the enzyme lysophosphatidylcholine acyltransferase (LPCAT) in the presence of Acyl-CoA
LPCAT contributes to reducing LPC levels; the overexpression of LPCAT is associated with cancer
Summary
General Features of Lysophosphatidylcholine Lysophosphatidylcholine (LPC), called lysolecithins, is a class of lipid biomolecule derived by the cleaving of phosphatidylcholine (PC) via the action of phospholipase A2 (PLA2) [1,2] and/or by the transfer of fatty acids to free cholesterol via lecithin-cholesterol acyltransferase (LCAT) [3]. LPCs can be produced in the circulation when PLA2 cleaves PCs, they can be converted back to PCs by the enzyme lysophosphatidylcholine acyltransferase (LPCAT) in the presence of Acyl-CoA. These two pathways are part of the Lands cycle [9], which is one of the body’s mechanisms for the cyclical synthesis and degradation of PC. LPCATs are intracellular enzymes found in body tissues such as lung [10], liver [11], and adipose tissue [12], but these intracellular enzymes are unlikely to interact directly with extracellular circulating LPC, which is positively associated with diseases [4,5,6]
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