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Phospholipids, are a class of
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
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 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 orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
group and two
hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...
"tails" derived from
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s, joined by an alcohol residue (usually a
glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
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. Phospholipids are a key component of all
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s. 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. Bacter ...
s, cell membranes also contain another class of lipid, sterol, 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 ...
and materials science. 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.


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 In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
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 Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
or
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s,
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 conne ...
s, sterols) 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 The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
. 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 observations regarding the structure of functional cell membranes. According to this biological model, there is a lipid bilayer (two molecules thick layer consisting primarily of amphipathic phospholipids ...
, 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. 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.


Main phospholipids


Diacylglyceride structures

: ''See: Glycerophospholipid'' * Phosphatidic acid (phosphatidate) (PA) * Phosphatidylethanolamine (cephalin) (PE) * Phosphatidylcholine (lecithin) (PC) * Phosphatidylserine (PS) * Phosphoinositides: **
Phosphatidylinositol Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
(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 A route of administration in pharmacology and toxicology 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 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, emulsion#Emulsifiers , ...
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 ca ...
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 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 dynamic "evolution" of th ...
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 GROningen MOlecular Simulation (GROMOS) is the name of a force field for molecular dynamics simulation, and a related computer software package. Both are developed at the University of Groningen, and at the Computer-Aided Chemistry Group at the ...
, CHARMM, or
AMBER Amber is fossilized tree resin that has been appreciated for its color and natural beauty since Neolithic times. Much valued from antiquity to the present as a gemstone, amber is made into a variety of decorative objects."Amber" (2004). In M ...
.


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 birefri ...
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 Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fi ...
, particularly 31P-NMR, while HPLC- 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 Distearoylphosphatidylcholine is a phosphatidylcholine, a kind of phospholipid. It is a natural constituent of cell membranes, eg. soybean phosphatidylcholines are mostly different 18-carbon phosphatidylcholines (including minority of saturated DS ...
, dioleoyl-3-trimethylammonium propane 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 m ...
in
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 Gq 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 dependi ...
in neurons to leukocyte 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 additi ...
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 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 isolate ...
, a plant hormone 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 with water. Phospholipids are one of the components of lecithin, 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, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu ...
s, 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.


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


See also

* Cable theory * Galactolipid *
Sulfolipid Sulfolipids are a class of lipids which possess a sulfur-containing functional group. An abundant sulfolipid is sulfoquinovosyl diacylglycerol, which is composed of a glycoside of sulfoquinovose and diacylglycerol. In plants, sulfoquinovosyl ...
* Hydrophile * Glycolipids


References

{{Authority control Anionic surfactants