Lysophosphatidylcholine
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Lysophosphatidylcholine
Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines. Overview Lysophosphatidylcholines are produced within cells mainly by the enzyme phospholipase A2, which removes one of the fatty acid groups from phosphatidylcholine to produce LPC. Among other properties, they activate endothelial cells during early atherosclerosis. LPC also acts as a find-me signal, released by apoptotic cells to recruit phagocytes, which then phagocytose the apoptotic cells 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. LPC-induced demyelination is thought to occur through the actions of recruited macrophages and microglia which phagocytose nearby myelin. Invading T cells are also t ...
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1-Lysophosphatidylcholine
2-acyl-sn-glycero-3-phosphocholines are a class of phospholipids that are intermediates in the metabolism of lipids. Because they result from the hydrolysis of an acyl group from the ''sn-1'' position of phosphatidylcholine, they are also called 1-lysophosphatidylcholine (or 1-lysoPC, in short). The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product. Other synonyms for this class of compounds are 2-acylglycero-3-phosphocholine, 1-lyso-2-acyl-sn-glycero-3-phosphocholine, β-lysophosphatidylcholine, 2-acylglycerophosphocholine, L-1-lysolecithin and 1-lecithin. Chemical properties 1-LysoPC can convert to the structurally similar 2-lysoPC. This happens by the migration of the acyl group from the ''sn-1'' position of the glycerol backbone to the ''sn-2'' position. The lowest rate of isomerization is at pH 4-5. Starting from either 1-lysoPC or 2-lysoPC, an equi ...
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Find-me Signals
Find-me signals Cells destined for apoptosis release molecules referred to as find me signals. These signal molecules are used to attract phagocytes which engulf and eliminate damaged cells. Find-me signals are typically released by the apoptotic cells while the cell membrane remains intact. This ensures that the phagocytic cells are able to remove the dying cells before their membranes are compromised. A leaky membrane leads to secondary necrosis which may cause additional inflammation, therefore, it is best to remove dying cells before this occurs. One cell is capable of releasing multiple find-me signals. Should a cell lack the ability to release its find-me signal, other cells may release additional find-me signals to overcome the discrepancy. Additional roles of Find-me signals Inflammation can be suppressed by find-me signals during cell clearance. A phagocyte may also be able to engulf more material or enhance its ability to engulf materials when stimulated by find-me signal ...
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Lysophospholipase
The enzyme lysophospholipase (EC 3.1.1.5) catalyzes the reaction :2-lysophosphatidylcholine + H2O \rightleftharpoons glycerophosphocholine + a carboxylate This enzyme belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. This family consists of lysophospholipase / phospholipase B (EC 3.1.1.5) and cytosolic phospholipase A2 which also has a C2 domain . Phospholipase B enzymes catalyse the release of fatty acids from lysophospholipids and are capable ''in vitro'' of hydrolyzing all phospholipids extractable from yeast cells. Cytosolic phospholipase A2 associates with natural membranes in response to physiological increases in Ca2+ and selectively hydrolyses arachidonyl phospholipids, the aligned region corresponds the carboxy-terminal Ca2+-independent catalytic domain of the protein as discussed in. The systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a sp ...
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Edelfosine
Edelfosine (ET-18-O-CH3; 1-octadecyl-2-''O''-methyl-glycero-3-phosphocholine) is a synthetic alkyl-lysophospholipid (ALP). It has antineoplastic (anti-cancer) effects. Like all ALPs, it incorporates into the cell membrane and does not target the DNA. In many tumor cells, it causes selective apoptosis, sparing healthy cells. Edelfosine can activate the Fas/CD95 cell death receptor, can inhibit the MAPK/ERK mitogenic pathway and the Akt/protein kinase B (PKB) survival pathway. Aside from these plasma-level effects, edelfosine also affects gene expression by modulating the expression and activity of transcription factors. It has immune modulating properties. These characteristics cause edelfosine also to affect HIV, parasitic, and autoimmune diseases. It can complement classic anti-cancer drugs such as cisplatin. It can be administered orally, intraperitoneally (IP) and intravenously (IV). Edelfosine and other ALPs can be used for purging residual leukemic cells from bon ...
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Alkyl-lysophospholipids
Alky-lysophospholipids (ALPs) are synthetic analogs of lysophosphatidylcholines (LPCs), also called lysolecithins. They are synthesized by replacing the acyl-group within the LPC with an alkyl group. In contrast to LPCs, ALPs are metabolically very stable. ALPs are being studied for their potential antineoplastic (anti-cancer) and immune-modulating effects. Their anti-tumor effects are due to modulation of intracellular signalling pathways, inducing apoptosis. It is highly selective, sparing healthy cells. Several examples including edelfosine, miltefosine, and perifosine are under development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped *Photographi ... as drugs against cancer and other diseases. References {{Reflist Experimental cancer drugs Lipids ...
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LPCAT1
Lysophosphatidylcholine acyltransferase 1 is a protein in humans that is encoded by the LPCAT1 gene. Lysophosphatidylcholine (LPC) acyltransferase (LPCAT; EC 2.3.1.23) catalyzes the conversion of LPC to phosphatidylcholine Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ... (PC) in the remodeling pathway of PC biosynthesis. References Genes on human chromosome 5 {{gene-5-stub ...
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Structure Lysophosphatidylcholine
A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as biological organisms, minerals and chemicals. Abstract structures include data structures in computer science and musical form. Types of structure include a hierarchy (a cascade of one-to-many relationships), a network featuring many-to-many links, or a lattice featuring connections between components that are neighbors in space. Load-bearing Buildings, aircraft, skeletons, anthills, beaver dams, bridges and salt domes are all examples of load-bearing structures. The results of construction are divided into buildings and non-building structures, and make up the infrastructure of a human society. Built structures are broadly divided by their varying design approaches and standards, into categories including building structures, archi ...
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Blood Plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6–8%; e.g., serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (, , , , , etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders. Blood plasma is separated from the blood by spinning a vessel of fresh blood containing an anticoagulant in a centrifuge until the blood cells fall to the bottom of the tube. The blood plasma is t ...
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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 in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially m ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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Perifosine
Perifosine (also KRX-0401) is a former drug candidate that was under development for a variety of cancer indications. It is an alkyl-phospholipid structurally related to miltefosine. Perifosine interrupts the PI3K/AKT/mTOR pathway by acting as an allosteric AKT inhibitor targeting the pleckstrin homology domain of AKT. It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.Smartoncology newsletter
, Feb 2010
In 2010, perifosine received orphan drug status in the U.S. for the treatment of multiple myeloma and neuroblastoma, and for multiple myeloma in the EU. However, both were later withdrawn. In 2011 it was in a phase III trial for colorectal cancer, and another for multiple myeloma. On April 2, 2012, it ...
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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 leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth. Common side effects include vomiting, abdominal pain, fever, headaches, and decreased kidney function. More severe side effects may include Stevens–Johnson syndrome or low blood platelets. Use during pregnancy appears to cause harm to the baby and use during breastfeeding is not recommended. How it works is not entirely clear. Miltefosine was first made in the early 1980s and studied as a treatment for cancer. A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India. It is on the World Health Organization's List of Essential Medicines. Medical uses Leishma ...
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