Lysophosphatidylcholine
Encyclopedia
Lysophosphatidylcholines (LPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholine
s. 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
. LPC can be used in the lab to cause demyelination of brain slices, to mimic the effects of demyelinating diseases such as multiple sclerosis
. Among other properties, they stimulate phagocytosis and can change the surface properties of erythrocytes.
LPC is present as a minor phospholipid in the cell membrane
(≤ 3%) and in the blood plasma
(8-12%).
Since LPCs are quickly metabolized by lysophosholypase and LPC-acyltransferase, they last only shortly in vivo. Hence they were not utilized as medical drug.
By replacing the acyl-group within the LPC with an alkyl-group, alkyl-lysophospholipids
(ALP) were synthesized. These analogues of LPC are metabolically stable, and several such as edelfosine
, miltefosine
and perifosine
are under research and development as drugs against cancer and other diseases.
Their anti-cancer abilities 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.
Phosphatidylcholine
Phosphatidylcholines 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 soy beans from which they are mechanically extracted or chemically...
s. They result from partial hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of phosphatidylcholines, which removes one of the fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
groups. The hydrolysis is generally the result of the enzymatic action of phospholipase A2
Phospholipase A2
Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids...
. LPC can be used in the lab to cause demyelination of brain slices, to mimic the effects of demyelinating diseases such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. Among other properties, they stimulate phagocytosis and can change the surface properties of erythrocytes.
LPC is present as a minor phospholipid in the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
(≤ 3%) and in the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
(8-12%).
Since LPCs are quickly metabolized by lysophosholypase and LPC-acyltransferase, they last only shortly in vivo. Hence they were not utilized as medical drug.
By replacing the acyl-group within the LPC with an alkyl-group, alkyl-lysophospholipids
Alkyl-lysophospholipids
Alky-lysophospholipids are synthetic analogues of lysophosphatidylcholines , also called lysolecithins.They were synthesized by replacing the acyl-group within the LPC with an alkyl-group. They are in contrast to LPC metabolically very stable.,...
(ALP) were synthesized. These analogues of LPC are metabolically stable, and several such as edelfosine
Edelfosine
Edelfosine is a synthetic alkyl-lisophospholipid . It has antineoplastic effects....
, miltefosine
Miltefosine
Miltefosine is a phospholipid drug.Originally developed as an antineoplastic , it is finding use as an antiprotozoal drug...
and perifosine
Perifosine
Perifosine is a drug candidate being developed for a variety of cancer indications.It is an alkylphospholipid Perifosine is structurally related to miltefosine...
are under research and development as drugs against cancer and other diseases.
Their anti-cancer abilities are special since they do not target the cell DNA but insert into the plasma membrane and cause apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
through influencing several signal pathways. Therefore their effects are independent of the proliferation state of the tumor cell.