Phospholipids are a class of

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

s whose molecule has a

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

"head" containing a

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

group and two

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

"tails" derived from

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 ...

s, joined by an

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

residue (usually a

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

molecule). Marine phospholipids typically have

omega-3 fatty acid Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...

s EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as

choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

ethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is a naturally occurring organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorl ...

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...

. Phospholipids are a key component of all

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 ...

s. They can form

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cell (biology), cells. The cell membranes of almost all organisms and many viruses a ...

s because of their

amphiphilic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

characteristic. In

eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s, cell membranes also contain another class of lipid,

sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...

, interspersed among the phospholipids. The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in

nanotechnology Nanotechnology is the manipulation of matter with at least one dimension sized from 1 to 100 nanometers (nm). At this scale, commonly known as the nanoscale, surface area and quantum mechanical effects become important in describing propertie ...

and

materials science Materials science is an interdisciplinary field of researching and discovering materials. Materials engineering is an engineering field of finding uses for materials in other fields and industries. The intellectual origins of materials sci ...

. The first phospholipid identified in 1847 as such in biological tissues was

lecithin Lecithin ( ; from the Ancient Greek "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...

, or

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 ...

, in the egg yolk of chickens by the French chemist and pharmacist Theodore Nicolas Gobley.

Phospholipids in biological membranes

Arrangement

The phospholipids are

. The hydrophilic end usually contains a negatively charged phosphate group, and the hydrophobic end usually consists of two "tails" that are long

residues. In aqueous solutions, phospholipids are driven by hydrophobic interactions, which result in the fatty acid tails aggregating to minimize interactions with the water molecules. The result is often a

phospholipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a l ...

: a membrane that consists of two layers of oppositely oriented phospholipid molecules, with their heads exposed to the liquid on both sides, and with the tails directed into the membrane. That is the dominant structural motif of the membranes of all cells and of some other biological structures, such as vesicles or

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

coatings.

In biological membranes, the phospholipids often occur with other molecules (e.g.,

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

glycolipid Glycolipids () are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the c ...

s) in a bilayer such as a

. Lipid bilayers occur when hydrophobic tails line up against one another, forming a membrane of hydrophilic heads on both sides facing the water.

Dynamics

These specific properties allow phospholipids to play an important role in the cell membrane. Their movement can be described by the

fluid mosaic model The fluid mosaic model explains various characteristics regarding the structure of functional cell membranes. According to this Scientific model, biological model, there is a lipid bilayer (two molecules thick layer consisting primarily of Amphip ...

, which 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.

Sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...

s 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.

Main phospholipids

Diacylglyceride structures

: ''See:

Glycerophospholipid Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes in eukaryotic cells. They are a type of lipid, of which its composition affects membrane structure and properties. T ...

'' * Phosphatidic acid (phosphatidate) (PA) *

Phosphatidylethanolamine Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine, ''S''-Ade ...

(cephalin) (PE) *

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 ...

(lecithin) (PC) *

Phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via a ...

(PS) * Phosphoinositides: **

Phosphatidylinositol Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...

(PI) ** Phosphatidylinositol 3-phosphate (PI3P) ** Phosphatidylinositol 4-phosphate (PI4P) **

Phosphatidylinositol 5-phosphate Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling ...

(PI5P) **

Phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

(PIP2) **

Phosphatidylinositol (3,4,5)-trisphosphate Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)''P''3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid ...

(PIP3)

Phosphosphingolipids

: ''See

Sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sp ...

'' * Ceramide phosphorylcholine (

Sphingomyelin Sphingomyelin (SPH, ) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine hea ...

) (SPH) * Ceramide phosphorylethanolamine (

) (Cer-PE) * Ceramide phosphoryllipid

Applications

Phospholipids have been widely used to prepare liposomal, ethosomal and other nanoformulations of topical, oral and

parenteral In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

drugs for differing reasons like improved bio-availability, reduced toxicity and increased permeability across membranes. Liposomes are often composed of

-enriched phospholipids and may also contain mixed phospholipid chains with

surfactant Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word ''surfactant'' is a Blend word, blend of "surface-active agent", coined in ...

properties. The ethosomal formulation of

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

using phospholipids is a promising option for transdermal delivery in fungal infections. Advances in phospholipid research lead to exploring these biomolecules and their conformations using lipidomics.

Simulations

Computational simulations of phospholipids are often performed using

molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the Motion (physics), physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamics ( ...

with force fields such as GROMOS,

CHARMM Chemistry at Harvard Macromolecular Mechanics (CHARMM) is the name of a widely used set of force fields for molecular dynamics, and the name for the molecular dynamics simulation and analysis computer software package associated with them. The CH ...

, or

AMBER Amber is fossilized tree resin. Examples of it have been appreciated for its color and natural beauty since the Neolithic times, and worked as a gemstone since antiquity."Amber" (2004). In Maxine N. Lurie and Marc Mappen (eds.) ''Encyclopedia ...

Characterization

Phospholipids are optically highly

birefringent Birefringence, also called double refraction, is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are described as birefring ...

, i.e. their refractive index is different along their axis as opposed to perpendicular to it. Measurement of

birefringence Birefringence, also called double refraction, is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are described as birefrin ...

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 Dual-polarization interferometry (DPI) is an analytical technique that probes molecular layers adsorbed to the surface of a waveguide using the evanescent wave of a laser beam. It is used to measure the conformational change in proteins, or o ...

to quantify lipid order or disruption in supported bilayers.

Analysis

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

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...

, particularly ³¹P-NMR, while

HPLC High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can origina ...

- ELSD provides relative values.

Phospholipid synthesis

Phospholipid synthesis occurs in the cytosolic side of 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.

Sources

Common sources of industrially produced phospholipids are soya, rapeseed, sunflower, chicken eggs, bovine milk, fish eggs etc. Phospholipids for gene delivery, such as distearoylphosphatidylcholine and dioleoyl-3-trimethylammonium propane, are produced synthetically. Each source has a unique profile of individual phospholipid species, as well as fatty acids, and consequently differing applications in food, nutrition, pharmaceuticals, cosmetics, and drug delivery.

In signal transduction

Some types of phospholipid can be split to produce products that function as

second messengers Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

. Examples include phosphatidylinositol (4,5)-bisphosphate (PIP₂), that can be split by the enzyme phospholipase C into

inositol triphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

(IP₃) and diacylglycerol (DAG), which both carry out the functions of the G_q type of G protein in response to various stimuli and intervene in various processes from long term depression in neurons to

leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

signal pathways started by

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

receptors. Phospholipids also intervene in

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

signal pathways as the raw material used by

lipase In biochemistry, lipase ( ) refers to a class of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; howe ...

enzymes to produce the prostaglandin precursors. In plants they serve as the raw material to produce jasmonic acid, a

plant hormone Plant hormones (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, including embryogenesis, the regulation of Organ (anat ...

similar in structure to prostaglandins that mediates defensive responses against pathogens.

Food technology

Phospholipids can act as

emulsifiers An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although ...

, enabling oils to form a

colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exte ...

with water. Phospholipids are one of the components of

, which is found in egg yolks, as well as being extracted from

soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean. Soy is a staple crop, the world's most grown legume, and an important animal feed. Soy is a key source o ...

s, and is used as a

food additive Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives, such as vinegar ( pickling), salt ( salting), smoke ( smoking) and sugar ( crystallization), have been used f ...

in many products and can be purchased as a

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

. Lysolecithins are typically used for water–oil emulsions like

margarine Margarine (, also , ) is a Spread (food), spread used for flavoring, baking, and cooking. It is most often used as a substitute for butter. Although originally made from animal fats, most margarine consumed today is made from vegetable oil. The ...

, due to their higher HLB ratio.

Phospholipid derivatives

: ''See table below for an extensive list.'' * Natural phospholipid derivates: *: egg PC ( Egg lecithin), egg PG, soy PC, hydrogenated soy PC,

sphingomyelin Sphingomyelin (SPH, ) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine hea ...

as natural phospholipids. * Synthetic phospholipid derivates: ** Phosphatidic acid (DMPA, DPPA, DSPA) **

(DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC) ** Phosphatidylglycerol (DMPG, DPPG, DSPG, POPG) **

(DMPE, DPPE, DSPE DOPE) **

(DOPS) ** PEG phospholipid (mPEG-phospholipid, polyglycerin-phospholipid, functionalized-phospholipid, terminal activated-phospholipid)

Abbreviations used and chemical information of glycerophospholipids

References

{{Authority control Anionic surfactants