Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from

phosphatidylcholine Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can easily be obtained from a variety of readily available sources, such as egg yolk or soyb ...

Overview

Lysophosphatidylcholines are produced within cells mainly by the enzyme

phospholipase A2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyses the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid "tail" and the glycero ...

, which removes one of the

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

groups from phosphatidylcholine to produce LPC. Among other properties, they activate endothelial cells during early

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

. LPC also acts as a find-me signal, released by apoptotic cells to recruit

phagocytes Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...

, which then phagocytose the apoptotic cells. Moreover, LPCs can be used in the lab to cause demyelination of brain slices and to mimic the effects of demyelinating diseases such as

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. LPCs are also known to stimulate phagocytosis of the

myelin sheath Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

and can change the surface properties of

erythrocytes Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

. LPC-induced demyelination is thought to occur through the actions of recruited

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

and

microglia Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...

which phagocytose nearby

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

. Invading T cells are also thought to mediate this process. Bacteria such as ''

Legionella pneumophila ''Legionella pneumophila'', the primary causative agent for Legionnaires' disease, Legionnaire's disease, is an Aerobic organism, aerobic, pleomorphic, Flagellum, flagellated, non-spore-forming, Gram-negative bacteria, Gram-negative bacterium. ' ...

'' utilize phospholipase A2 end-products (fatty acids and lysophospholipids) to cause host cell (macrophage) apoptosis through cytochrome C release. LPCs are present as minor phospholipids in the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

(≤ 3%) and in the

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

(8–12%). Since LPCs are quickly metabolized by lysophospholipase and LPC-acyltransferase, they last only shortly ''in vivo''. By replacing the acyl-group within the LPC with an alkyl-group, alkyl-lysophospholipids (ALP) were synthesized. These LPC analogues are metabolically stable, and several ALPs such as edelfosine,

miltefosine Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as '' Naegleria fowleri'' and '' Balamuthia mandrillaris''. This includes the three forms of ...

and perifosine are under research and development as drugs against cancer and other diseases. Lysophosphatidylcholine processing has been discovered to be an essential component of normal human brain development: those born with genes that prevent adequate uptake suffer from lethal microcephaly. MFSD2a has been shown to transport LPC-bound polyunsaturated fatty acids, including DHA and EPA, across the blood-brain and blood-retinal barriers. LPCs occur in many foods naturally. According to the third edition of ''Starch: Chemistry and Technology'', lysophosphatidylcholine makes up about 70% of the lipids in oat starch (p.592). Also, the anti-cancer abilities of synthetic LPC variants are special since they do not target the cell DNA but rather insert into the plasma membrane, causing

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

through the influencing of several signal pathways. Therefore, their effects are independent of the proliferation state of the

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cell.

Industrial applications of PLA2

FoodPro LysoMaxa Oil is an FDA approved commercialized PLA2 enzyme preparation utilized for the degumming of vegetable oils in large-scale productions to increase yield. Variants of lysophosphatidylcholine are the main products of this enzyme.

Applications

Lysophosphatidylcholine has been studied as an immune activator for differentiating monocytes to mature dendritic cells. Lysophosphatidylcholine present in blood amplifies microbial TLR ligands-induced inflammatory responses from human cells like intestinal epithelial cells and macrophages/monocytes. This has an implication in sepsis induced by microbes.

Occurrence in foods

Lysophosphatidylcholine accounts for 4.6% of phospholipids found in coconut oil, which make up 0.2% of lipids in coconut oil. In contrast, vegetable oils contain about 2-3% phospholipids.

Production in atherosclerosis

Intima-media thickness, which is positively correlated with reduced blood flow, was studied in young smokers. Evidence pointed towards smoking as a major risk factor for increased levels of PLA2, due to tobacco smoke's impact on oxidation of retained LDL particles in the intima of a carotid artery, which may have a detrimental impact on overall health.

References