Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

residue (usually a glycerol molecule). Marine phospholipids typically have omega-3 fatty acids

EPA The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...

and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or

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 − form un ...

. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s, cell membranes also contain another class of lipid,

sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...

, 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, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal o ...

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

lecithin Lecithin (, from the Greek ''lekithos'' "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, in the egg yolk of chickens by the French chemist and pharmacist Theodore Nicolas Gobley.

Phospholipids in biological membranes

Arrangement

The phospholipids are amphiphilic. The hydrophilic end usually contains a negatively charged phosphate group, and the hydrophobic end usually consists of two "tails" that are long fatty acid 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: 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 Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

and of some other biological structures, such as vesicles or virus coatings. Cell membrane detailed diagram 4

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

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 connec ...

s) in a

bilayer A bilayer is a double layer of closely packed atoms or molecules. The properties of bilayers are often studied in condensed matter physics, particularly in the context of semiconductor devices, where two distinct materials are united to form junc ...

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.

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, 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 Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...

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'' *

Phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty ac ...

(phosphatidate) (PA) * Phosphatidylethanolamine (cephalin) (PE) * Phosphatidylcholine (lecithin) (PC) * Phosphatidylserine (PS) * Phosphoinositides: ** Phosphatidylinositol (PI) ** Phosphatidylinositol phosphate (PIP) ** Phosphatidylinositol bisphosphate (PIP2) and ** Phosphatidylinositol trisphosphate (PIP3)

Phosphosphingolipids

: ''See Sphingolipid'' * Ceramide phosphorylcholine ( Sphingomyelin) (SPH) * Ceramide phosphorylethanolamine ( Sphingomyelin) (Cer-PE) * Ceramide phosphoryllipid

Applications

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 Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...

properties. The ethosomal formulation of

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

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 with

force fields Force field may refer to: Science * Force field (chemistry), a set of parameter and equations for use in molecular mechanics simulations * Force field (physics), a vector field indicating the forces exerted by one object on another * Force field ( ...

such as GROMOS, CHARMM, or AMBER.

Characterization

Phospholipids are optically highly birefringent, i.e. their refractive index is different along their axis as opposed to perpendicular to it. Measurement of

birefringence Birefringence 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 said to be birefringent (or birefractive). The birefring ...

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.

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, 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 each component in a mixture. It relies on pumps to pa ...

- 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,

dioleoyl-3-trimethylammonium propane 1,2-Dioleoyl-3-trimethylammonium propane (often abbreviated DOTAP or 18:1TAP) is a di-chain, or gemini, cationic surfactant. It is most commonly encountered as an active ingredient in certain fabric softeners. The pure material can also be us ...

etc. 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 or cell signaling, encompassing both first me ...

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

. 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 G_q type of G protein in response to various stimuli and intervene in various processes from

long term depression In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depend ...

in neurons to

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

signal pathways started by chemokine receptors. Phospholipids also intervene in

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

signal pathways as the raw material used by

lipase Lipase ( ) is a family 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; however, these are usually tr ...

enzymes to produce the prostaglandin precursors. In plants they serve as the raw material to produce

jasmonic acid Jasmonic acid (JA) is an organic compound found in several plants including jasmine. The molecule is a member of the jasmonate class of plant hormones. It is biosynthesized from linolenic acid by the octadecanoid pathway. It was first isolat ...

, a

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

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

Food technology

Phospholipids can act as emulsifiers, 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 extend ...

with water. Phospholipids are one of the components of

, which is found in egg yolks, as well as being extracted from soybeans, 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 have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...

in many products and can be purchased as a

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

. Lysolecithins are typically used for water–oil emulsions like

margarine Margarine (, also , ) is a 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 spread was orig ...

, due to their higher HLB ratio.

Phospholipid derivatives

: ''See table below for an extensive list.'' * Natural phospholipid derivates: *: egg PC (

Egg lecithin Egg lecithin is a type of lecithin, a group of compounds primarily containing phospholipids, that is derived from eggs. Discovery Egg lecithin was first isolated in 1846 by the French chemist and pharmacist Theodore Gobley. Gobley originally ...

), egg PG, soy PC, hydrogenated soy PC, sphingomyelin as natural phospholipids. * Synthetic phospholipid derivates: **

(DMPA, DPPA, DSPA) ** Phosphatidylcholine (DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC) ** Phosphatidylglycerol (DMPG, DPPG, DSPG, POPG) ** Phosphatidylethanolamine (DMPE, DPPE, DSPE DOPE) ** Phosphatidylserine (DOPS) ** PEG phospholipid (mPEG-phospholipid, polyglycerin-phospholipid, functionalized-phospholipid, terminal activated-phospholipid)

Abbreviations used and chemical information of glycerophospholipids

References

{{Authority control Anionic surfactants