Lysophosphatidylcholine

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General chemical structure of lysophosphatidylcholines, where R is a variable fatty acid chain

Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines.[1]

Overview[edit]

They result from partial hydrolysis of phosphatidylcholines, which removes one of the fatty acid groups. The hydrolysis is generally the result of the enzymatic action of phospholipase A2.[2] Among other properties, they activate endothelial cells during early atherosclerosis[3][4] and stimulate phagocyte recruitment when released by apoptotic cells.[5] Moreover, LPCs can be used in the lab to cause demyelination of brain slices, to mimic the effects of demyelinating diseases such as multiple sclerosis. Further, they are known to stimulate phagocytosis of the myelin sheath and can change the surface properties of erythrocytes.[6] LPC-induced demyelination is thought to occur through the actions of recruited macrophages and microglia which phagocytose nearby myelin. Invading T cells are also thought to mediate this process. Bacteria such as Legionella pneumophila 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 (≤ 3%) and in the blood plasma (8–12%).[6] 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 such as edelfosine, miltefosine and perifosine are under research and development as drugs against cancer and other diseases.[6][7] 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.[8]

LPCs occur in many foods naturally. In Starch: Chemistry and Technology third edition on page 592, the authors state that "lysophosphatidylcholine makes up about 70% of the lipids in oat starch".[9]

The anti-cancer abilities of synthetic LPC variants are special since they do not target the cell DNA but insert into the plasma membrane and cause apoptosis through influencing several signal pathways. Therefore, their effects are independent of the proliferation state of the tumor cell.[10]

Industrial Applications of Enzymes Producing Lysophosphatidylcholine[edit]

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. [11] Lysophosphatidylcholine has been studied as an immune activator for differentiating monocytes to mature dendritic cells.[12]

Composition in Foods[edit]

Lysophosphatidylcholine accounts for 4.6% of phospholipids found in coconut oil, which make up 0.2% of lipids in coconut oil. This is compared to vegetable oils, which may contain 2-3% phospholipids.[13]

Lysophosphatidylcholine and Atherosclerosis[edit]

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.[14] which may have a detrimental impact on overall health.

See also[edit]

References[edit]

  1. ^ Li X, Wang L, Fang P, et al. (May 2018). "Lysophospholipids induce innate immune transdifferentiation of endothelial cells, resulting in prolonged endothelial activation". The Journal of Biological Chemistry. 293 (28): 11033–11045. doi:10.1074/jbc.RA118.002752. PMC 6052225. PMID 29769317.
  2. ^ Phosphatidylcholine and related lipids Archived 2009-05-31 at the Wayback Machine, lipidlibrary.co.uk
  3. ^ Li X, Fang P, et al. (April 2016). "Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation". Arteriosclerosis, Thrombosis, and Vascular Biology. 36 (6): 1090–100. doi:10.1161/ATVBAHA.115.306964. PMC 4882253. PMID 27127201.
  4. ^ Li X, Shao Y, Fang P, et al. (March 2018). "IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14)". Arteriosclerosis, Thrombosis, and Vascular Biology. 38 (3): 599–609. doi:10.1161/ATVBAHA.117.310626. PMC 5823772. PMID 29371247.
  5. ^ Lauber, K; Bohn, E; Kröber, SM; Xiao, Y (2003). "Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal". Cell. 113 (6): 717–730. doi:10.1016/S0092-8674(03)00422-7. PMID 12809603.
  6. ^ a b c Munder, PG; Modolell M; Andreesen R; Weltzien HU; Westphal O (1979). "Lysophosphatidylcholine (Lysolecithin) and its Synthetic Analogues . Immunemodulating and Other Biologic Effects". Springer Seminars in Immunopathology. 203 (2): 187–203. doi:10.1007/bf01891668.
  7. ^ Houlihan, W; Lohmeyer M; Workman P; Cheon SH (1995). "Phospholipid antitumor agents". Medicinal Research Reviews. 15 (3): 157–223. doi:10.1002/med.2610150302. PMID 7658750.
  8. ^ Guemez-Gamboa, Alicia; N Nguyen; Hongbo Yan (2015). "Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome". Nature Genetics. 47 (7): 809–813. doi:10.1038/ng.3311. PMC 4547531. PMID 26005868.
  9. ^ Bemiller, James N.; Whistler, Roy L. (2009-04-06). Starch. ISBN 9780080926551.
  10. ^ van Blitterswijk, W; Verheij M (2008). "Anticancer alkylphospholipids: mechanisms of action, cellular sensitivity and resistance, and clinical prospects". Current Pharmaceutical Design. 14 (21): 2061–74. doi:10.2174/138161208785294636. PMID 18691116.
  11. ^ Michael Eskin, N. A.; Shahidi, Fereidoon (2012-10-08). Biochemistry of Foods. ISBN 9780080918099.
  12. ^ "Patent US20110135684 - Use of L-alpha-lysophosphatidylcholine to obtain the differentiation of ... - Google Patents". google.com.mx.
  13. ^ "Rahman's page 12 chart" (PDF). Archived from the original (PDF) on 2014-03-28.
  14. ^ Fratta Pasini, A; Stranieri, C; Pasini, A; Vallerio, P; Mozzini, C; Solani, E; Cominacini, M; Cominacini, L; Garbin, U (2013). "Lysophosphatidylcholine and Carotid Intima-Media Thickness in Young Smokers: A Role for Oxidized LDL-Induced Expression of PBMC Lipoprotein-Associated Phospholipase A2?". PLOS ONE. 8 (12): e83092. doi:10.1371/journal.pone.0083092. PMC 3866188. PMID 24358251.