Phospholipids are a class of lipids that are a major component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. The structure of the phospholipid molecule generally consists of two hydrophobic fatty acid "tails" and a hydrophilic "head" consisting of a phosphate group. The two components are joined together by a glycerol molecule. The phosphate groups can be modified with simple organic molecules such as choline, ethanolamine or serine.
The first phospholipid identified in 1847 as such in biological tissues was lecithin, or phosphatidylcholine, in the egg yolk of chickens by the French chemist and pharmacist, Theodore Nicolas Gobley. Biological membranes in eukaryotes also contain another class of lipid, sterol, interspersed among the phospholipids and together they provide membrane fluidity and mechanical strength. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science.
An amphiphile (from the Greek αμφις, amphis: both and φιλíα, philia: love, friendship; also termed "amphipathic") is a term describing a chemical compound possessing both hydrophilic (water-loving, polar) and lipophilic (fat-loving, non-polar) properties. The phospholipid head contains a negatively charged phosphate group and glycerol; it is hydrophilic. The phospholipid tails usually consist of 2 long fatty acid chains; they are hydrophobic and avoid interactions with water. When placed in aqueous solutions, phospholipids are driven by hydrophobic interactions that result in the fatty acid tails aggregating to minimize interactions with water molecules. These specific properties allow phospholipids to play an important role in the phospholipid bilayer. In biological systems, the phospholipids often occur with other molecules (e.g., proteins, glycolipids, sterols) in a bilayer such as a cell membrane. Lipid bilayers occur when hydrophobic tails line up against one another, forming a membrane of hydrophilic heads on both sides facing the water.
Such movement can be described by the fluid mosaic model, that describes the membrane as a mosaic of lipid molecules that act as a solvent for all the substances and proteins within it, so proteins and lipid molecules are then free to diffuse laterally through the lipid matrix and migrate over the membrane. Sterols contribute to membrane fluidity by hindering the packing together of phospholipids. However, this model has now been superseded, as through the study of lipid polymorphism it is now known that the behaviour of lipids under physiological (and other) conditions is not simple.
Phospholipids have been widely used to prepare liposomal, ethosomal and other nanoformulations of topical, oral and parenteral drugs for differing reasons like improved bio-availability, reduced toxicity and increased permeability across membranes. Liposomes are often composed of phosphatidylcholine-enriched phospholipids and may also contain mixed phospholipid chains with surfactant properties. The ethosomal formulation of ketoconazole using phospholipids is a promising option for transdermal delivery in fungal infections.
Phospholipids are optically highly birefringent, i.e. their refractive index is different along their axis as opposed to perpendicular to it. Measurement of birefringence can be achieved using cross polarisers in a microscope to obtain an image of e.g. vesicle walls or using techniques such as dual polarisation interferometry to quantify lipid order or disruption in supported bilayers.
There are no simple methods available for analysis of phospholipids since the close range of polarity between different phospholipid species makes detection difficult. Oil chemists often use spectroscopy to determine total Phosphorus abundance and then calculate approximate mass of phospholipids based on molecular weight of expected fatty acid species. Modern lipid profiling employs more absolute methods of analysis, with nuclear magnetic resonance spectroscopy (NMR spectroscopy), particularly 31P-NMR, while HPLC-ELSD provides relative values.
Phospholipid synthesis occurs in the cytosole adjacent to ER membrane that is studded with proteins that act in synthesis (GPAT and LPAAT acyl transferases, phosphatase and choline phosphotransferase) and allocation (flippase and floppase). Eventually a vesicle will bud off from the ER containing phospholipids destined for the cytoplasmic cellular membrane on its exterior leaflet and phospholipids destined for the exoplasmic cellular membrane on its inner leaflet.
Common sources of industrially produced phospholipids are soya, rapeseed, sunflower, chicken eggs, bovine milk, fish eggs etc. Each source has a unique profile of individual phospholipid species and consequently differing applications in food, nutrition, pharmaceuticals, cosmetics and drug delivery.
Some types of phospholipid can be split to produce products that function as second messengers in signal transduction. Examples include phosphatidylinositol (4,5)-bisphosphate (PIP2), that can be split by the enzyme Phospholipase C into inositol triphosphate (IP3) and diacylglycerol (DAG), which both carry out the functions of the Gq type of G protein in response to various stimuli and intervene in various processes from long term depression in neurons to leukocyte signal pathways started by chemokine receptors.
Phospholipids also intervene in prostaglandin signal pathways as the raw material used by lipase enzymes to produce the prostaglandin precursors. In plants they serve as the raw material to produce Jasmonic acid, a plant hormone similar in structure to prostaglandins that mediates defensive responses against pathogens.
Phospholipids can act as emulsifiers, enabling oils to form a colloid with water. Phospholipids are one of the components of lecithin which is found in egg-yolks, as well as being extracted from soy beans, and is used as a food additive in many products, and can be purchased as a dietary supplement. Lysolecithins are typically used for water-oil emulsions like margarine, due to their higher HLB ratio.
|DEPA-NA||80724-31-8||1,2-Dierucoyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DEPG-NA||1,2-Dierucoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DLPA-NA||1,2-Dilauroyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DLPG-NA||1,2-Dilauroyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DLPG-NH4||1,2-Dilauroyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)||Phosphatidylglycerol|
|DLPS-NA||1,2-Dilauroyl-sn-glycero-3-phosphoserine (Sodium Salt)||Phosphatidylserine|
|DMPA-NA||80724-3||1,2-Dimyristoyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DMPG-NA||67232-80-8||1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DMPG-NH4||1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)||Phosphatidylglycerol|
|DMPG-NH4/NA||1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium/Ammonium Salt)||Phosphatidylglycerol|
|DMPS-NA||1,2-Dimyristoyl-sn-glycero-3-phosphoserine (Sodium Salt)||Phosphatidylserine|
|DOPA-NA||1,2-Dioleoyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DOPG-NA||62700-69-0||1,2-Dioleoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DOPS-NA||70614-14-1||1,2-Dioleoyl-sn-glycero-3-phosphoserine (Sodium Salt)||Phosphatidylserine|
|DPPA-NA||71065-87-7||1,2-Dipalmitoyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DPPG-NA||67232-81-9||1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DPPG-NH4||73548-70-6||1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)||Phosphatidylglycerol|
|DPPS-NA||1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (Sodium Salt)||Phosphatidylserine|
|DSPA-NA||108321-18-2||1,2-Distearoyl-sn-glycero-3-phosphate (Sodium Salt)||Phosphatidic acid|
|DSPG-NA||67232-82-0||1,2-Distearoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Sodium Salt)||Phosphatidylglycerol|
|DSPG-NH4||108347-80-4||1,2-Distearoyl-sn-glycero-3[Phospho-rac-(1-glycerol...) (Ammonium Salt)||Phosphatidylglycerol|
|DSPS-NA||1,2-Distearoyl-sn-glycero-3-phosphoserine (Sodium Salt)||Phosphatidylserine|
|HEPC||Hydrogenated Egg PC||Phosphatidylcholine|
|HSPC||Hydrogenated Soy PC||Phosphatidylcholine|
|Milk Sphingomyelin MPPC||1-Myristoyl-2-palmitoyl-sn-glycero 3-phosphocholine||Phosphatidylcholine|
|POPG-NA||81490-05-3||1-Palmitoyl-2-oleoyl-sn-glycero-3[Phospho-rac-(1-glycerol)...] (Sodium Salt)||Phosphatidylglycerol|
Probable phospholipid-transporting ATPase VA also known as ATPase class V type 10A (ATP10A) or aminophospholipid translocase VA is an enzyme that in humans is encoded by the ATP10A gene.ATP11B
Probable phospholipid-transporting ATPase IF is an enzyme that in humans is encoded by the ATP11B gene.ATP8B1
Probable phospholipid-transporting ATPase IC is an enzyme that in humans is encoded by the ATP8B1 gene. This protein is associated with progressive familial intrahepatic cholestasis type 1 as well as benign recurrent intrahepatic cholestasis.Antiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia.
The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two antibody blood tests spaced at least three months apart that confirm the presence of either lupus anticoagulant or anti-β2-glycoprotein-I (since β2-glycoprotein-I antibodies are a subset of anti-cardiolipin antibodies, an anti-cardiolipin assay can be performed as a less specific proxy).Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus (SLE). In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high risk of death.
Antiphospholipid syndrome often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin/Coumadin is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic.Antiporter
An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions. Na+/H+ antiporters have been reviewed.In secondary active transport, one species of solute moves along its electrochemical gradient, allowing a different species to move against its own electrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are moved against their concentration gradients, fueled by ATP.
Transport may involve one or more of each type of solute. For example, the Na+/Ca2+ exchanger, used by many cells to remove cytoplasmic calcium, exchanges one calcium ion for three sodium ions.Apolipoprotein H
Apolipoprotein H (Apo-H), previously known as β2-glycoprotein I and beta-2 glycoprotein I, is a 38 kDa multifunctional apolipoprotein that in humans is encoded by the APOH gene. One of its functions is to bind cardiolipin. When bound the structure of cardiolipin and Apo-H both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively charged amino acids (protein sequence positions 282-287), Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding (See image on right).Apo-H has a complex involvement in agglutination, it appears to alter adenosine diphosphate (ADP) mediated agglutination of platelets. Normally Apo-H assumes an anti-coagulation activity in serum (by inhibiting coagulation factors); however, changes in blood factors can result of a reversal of that activity.Barth syndrome
Barth syndrome (BTHS),is an X-linked genetic disorder. The disorder, which affects multiple body systems, is diagnosed almost exclusively in males. It is named after Dutch pediatric neurologist Peter Barth.Biological membrane
A biological membrane or biomembrane is an enclosing or separating membrane that acts as a selectively permeable barrier within living things. Biological membranes, in the form of eukaryotic cell membranes, consist of a phospholipid bilayer with embedded, integral and peripheral proteins used in communication and transportation of chemicals and ions. The bulk of lipid in a cell membrane provides a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning. Proteins are adapted to high membrane fluidity environment of lipid bilayer with the presence of an annular lipid shell, consisting of lipid molecules bound tightly to surface of integral membrane proteins. The cell membranes are different from the isolating tissues formed by layers of cells, such as mucous membranes, basement membranes, and serous membranes.Cyclopropane-fatty-acyl-phospholipid synthase
In enzymology, a cyclopropane-fatty-acyl-phospholipid synthase (EC 126.96.36.199) is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are S-adenosyl methionine and phospholipid olefinic fatty acid, whereas its two products are S-adenosylhomocysteine and phospholipid cyclopropane fatty acid.
This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:unsaturated-phospholipid methyltransferase (cyclizing). Other names in common use include cyclopropane synthetase, unsaturated-phospholipid methyltransferase, cyclopropane synthase, cyclopropane fatty acid synthase, cyclopropane fatty acid synthetase, and CFA synthase.Ether lipid
In an organic chemistry general sense, an ether lipid implies an ether bridge between an alkyl group (a lipid) and an unspecified alkyl or aryl group, not necessarily glycerol. If glycerol is involved, the compound is called a glyceryl ether, which may take the form of an alkylglycerol, an alkyl acyl glycerol, or in combination with a phosphatide group, a phospholipid.
In a biochemical sense, an ether lipid usually implies glycerophospholipids of various type, also called phospholipids, in which the sn-1 position of the glycerol backbone has a lipid attached by an ether bond and a lipid attached to the sn-2 position via an acyl group. This is in contrast to the more common glycerophospholipids, 1,2-diacyl-sn-glycerol (DAG), in which the glycerol backbone sn-1 and sn-2 positions have acyl chains attached by ester bonds. Ether lipid may also refer to alkylglycerols, such as chimyl (16:0), batyl (18:0), and selachyl (18:1 n-9) alcohols, with a ether-bound lipid on position sn-1, and the other two positions on the glycerol backbone unoccupied.Flippase
Flippases (rarely spelled flipases) are transmembrane lipid transporter proteins located in the membrane which belong to ABC transporter family. They are responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane (transverse diffusion, also known as a "flip-flop" transition). The possibility of active maintenance of an asymmetric distribution of molecules in the phospholipid bilayer was predicted in the early 1970s by Mark Bretscher. Although phospholipids diffuse rapidly in the plane of the membrane, their polar head groups cannot pass easily through the hydrophobic center of the bilayer, limiting their diffusion in this dimension. Some flippases - often instead called scramblases - are energy-independent and bidirectional, causing reversible equilibration of phospholipid between the two sides of the membrane, whereas others are energy-dependent and unidirectional, using energy from ATP hydrolysis to pump the phospholipid in a preferred direction. Flippases are described as transporters that move lipids from the exoplasmic to the cytosolic face, while floppases transport in the reverse direction.Many cells maintain asymmetric distributions of phospholipids between their cytoplasmic and exoplasmic membrane leaflets. The loss of asymmetry, in particular the appearance of the anionic phospholipid phosphatidylserine on the exoplasmic face, can serve as an early indicator of apoptosis. This effect has been observed in neurons as a response to amyloid beta peptides, thought to be a primary cause of the neurodegenerative effects of Alzheimer's disease.Hemolysis
Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo or in vitro (inside or outside the body).
Hemolysins damage the host cytoplasmic membrane, causing cell lysis and death. The activity of these toxins is most easily observed with assays involving the lysis of red blood cells (erythrocytes). Some hemolysins attack the phospholipid of the host cytoplasmic membrane. Because the phospholipid lecithin (phosphatidylcholine) is often used as a substrate, these enzymes are called lecithinases or phospholipases. Some hemolysins affects the sterols of the host cytoplasmic membrane.Lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and other membranes surrounding sub-cellular structures. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role, even though they are only a few nanometers in width, they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps.
Biological bilayers are usually composed of amphiphilic phospholipids that have a hydrophilic phosphate head and a hydrophobic tail consisting of two fatty acid chains. Phospholipids with certain head groups can alter the surface chemistry of a bilayer and can, for example, serve as signals as well as "anchors" for other molecules in the membranes of cells. Just like the heads, the tails of lipids can also affect membrane properties, for instance by determining the phase of the bilayer. The bilayer can adopt a solid gel phase state at lower temperatures but undergo phase transition to a fluid state at higher temperatures, and the chemical properties of the lipids' tails influence at which temperature this happens. The packing of lipids within the bilayer also affects its mechanical properties, including its resistance to stretching and bending. Many of these properties have been studied with the use of artificial "model" bilayers produced in a lab. Vesicles made by model bilayers have also been used clinically to deliver drugs.
Biological membranes typically include several types of molecules other than phospholipids. A particularly important example in animal cells is cholesterol, which helps strengthen the bilayer and decrease its permeability. Cholesterol also helps regulate the activity of certain integral membrane proteins. Integral membrane proteins function when incorporated into a lipid bilayer, and they are held tightly to lipid bilayer with the help of an annular lipid shell. Because bilayers define the boundaries of the cell and its compartments, these membrane proteins are involved in many intra- and inter-cellular signaling processes. Certain kinds of membrane proteins are involved in the process of fusing two bilayers together. This fusion allows the joining of two distinct structures as in the fertilization of an egg by sperm or the entry of a virus into a cell. Because lipid bilayers are quite fragile and invisible in a traditional microscope, they are a challenge to study. Experiments on bilayers often require advanced techniques like electron microscopy and atomic force microscopy.Lysophosphatidic acid
Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.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 soybeans, from which they are mechanically or chemically extracted using hexane. They are also a member of the lecithin group of yellow-brownish fatty substances occurring in animal and plant tissues. Dipalmitoyl phosphatidylcholine (a.k.a. lecithin) is a major component of pulmonary surfactant and is often used in the L/S ratio to calculate fetal lung maturity. While phosphatidylcholines are found in all plant and animal cells, they are absent in the membranes of most bacteria, including Escherichia coli. Purified phosphatidylcholine is produced commercially.
The name "lecithin" was originally defined from the Greek lekithos (λεκιθος, egg yolk) by Theodore Nicolas Gobley, a French chemist and pharmacist of the mid-19th century, who applied it to the egg yolk phosphatidylcholine that he identified in 1847. Gobley eventually completely described his lecithin from chemical structural point of view, in 1874. Phosphatidylcholines are such a major component of lecithin that in some contexts the terms are sometimes used as synonyms. However, lecithin extracts consist of a mixture of phosphatidylcholine and other compounds. It is also used along with sodium taurocholate for simulating fed- and fasted-state biorelevant media in dissolution studies of highly lipophilic drugs.
Phosphatidylcholine is a major constituent of cell membranes and pulmonary surfactant, and is more commonly found in the exoplasmic or outer leaflet of a cell membrane. It is thought to be transported between membranes within the cell by phosphatidylcholine transfer protein (PCTP).Phosphatidylcholine also plays a role in membrane-mediated cell signaling and PCTP activation of other enzymes.Phospholipase B
Phospholipase B, also known as lysophospholipase, is an enzyme with a combination of both PLA1 and PLA2 activities; that is, it can cleave acyl chains from both the sn-1 and sn-2 positions of a phospholipid. In general, it acts on lysolecithin (which is formed by the action of PLA2 on lecithin).Phospholipid scramblase
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are not members of the general family of transmembrane lipid transporters known as flippases. Scramblases are distinct from flippases and floppases. Scramblases, flippases, and floppases are three different types of enzymatic groups of phospholipid transportation enzymes. The inner-leaflet, facing the inside of the cell, contains negatively charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, that can transport (scramble) the negatively charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa.Phospholipid transfer protein
Phospholipid transfer protein is a protein that in humans is encoded by the PLTP gene.Phosphorylcholine
Phosphorylcholine refers to the functional group derived from phosphocholine. Also not to be confused with phosphatidylcholine.Phosphorylcholine (abbreviated ChoP) is the hydrophilic polar head group of some phospholipids, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is part of platelet-activating factor; the phospholipid phosphatidylcholine as well as sphingomyelin, the only phospholipid of the membrane that is not built with a glycerol backbone. Treatment of cell membranes, like those of RBCs, by certain enzymes, like some phospholipase A2 renders the phosphorylcholine moiety exposed to the external aqueous phase, and thus accessible for recognition by the immune system. Antibodies against phosphorylcholine are naturally occurring autoantibodies that are created by CD5+/B-1 B cells and are referred to as non-pathogenic autoantibodies.
Structures of the cell membrane