Phosphatidylethanolamine (PE) is a class of

phospholipid 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 residue (usually a glycerol molecule). Marine phospholipids typ ...

s found in

biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of th ...

s. They are synthesized by the addition of cytidine diphosphate-

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 ...

diglyceride A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. Diglycerides are ...

s, releasing

cytidine monophosphate Cytidine monophosphate, also known as 5'-cytidylic acid or simply cytidylate, and abbreviated CMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside cytidine. CMP consists of the phosphate grou ...

. ''S''-Adenosyl methionine can subsequently methylate the

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

of phosphatidylethanolamines to yield

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 ...

Function

In cells

Phosphatidylethanolamines are found in all living cells, composing 25% of all phospholipids. In human physiology, they are found particularly in nervous tissue such as the

white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

, nerves, neural tissue, and in

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

, where they make up 45% of all phospholipids. Phosphatidylethanolamines play a role in

membrane fusion In membrane biology, fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. If this fusion proceeds completely through both leaflets of both bilayers, an aqueou ...

and in disassembly of the

contractile ring In molecular biology, an actomyosin ring or contractile ring, is a prominent structure during cytokinesis. It forms perpendicular to the axis of the spindle apparatus towards the end of telophase, in which sister chromatids are identically separ ...

during

cytokinesis Cytokinesis () is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division ...

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

. Additionally, it is thought that phosphatidylethanolamine regulates membrane curvature. Phosphatidylethanolamine is an important precursor,

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

, or donor in several biological pathways. As a polar head group, phosphatidylethanolamine creates a more viscous lipid membrane compared to

. For example, the melting temperature of di-oleoyl-phosphatidylethanolamine is -16 °C while the melting temperature of di-oleoyl-phosphatidylcholine is -20 °C. If the lipids had two palmitoyl chains, phosphatidylethanolamine would melt at 63 °C while phosphatidylcholine would melt already at 41 °C. Lower melting temperatures correspond, in a simplistic view, to more fluid membranes.

In humans

In humans, metabolism of phosphatidylethanolamine is thought to be important in the heart. When blood flow to the heart is restricted, the asymmetrical distribution of phosphatidylethanolamine between membrane leaflets is disrupted, and as a result the membrane is disrupted. Additionally, phosphatidylethanolamine plays a role in the secretion of

lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

in the liver. This is because vesicles for secretion of

very low-density lipoprotein Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, LDL, low-density ...

s coming off of the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

have a significantly higher phosphatidylethanolamine concentration when compared to other vesicles containing very low-density lipoproteins. Phosphatidylethanolamine has also shown to be able to propagate infectious prions without the assistance of any

proteins 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, re ...

nucleic acids Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic a ...

, which is a unique characteristic of it. Phosphatidylethanolamine is also thought to play a role in blood clotting, as it works with

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 ...

to increase the rate of

thrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

formation by promoting binding to

factor V Coagulation factor V (Factor V), also less commonly known as proaccelerin or labile factor, is a protein involved in coagulation, encoded, in humans, by ''F5'' gene. In contrast to most other coagulation factors, it is not enzymatically active b ...

and

factor X Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for i ...

, two proteins which catalyze the formation of thrombin from

prothrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

. The synthesis of endocannabinoid

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

is performed from the phosphatidylethanolamine by the successive action of two enzymes, ''N''-

acetyltransferase An acetyltransferase (also referred to as a transacetylase) is any of a class of transferase enzymes that transfers an acetyl group in a reaction called acetylation. In biological organisms, post-translational modification of a protein via acetyl ...

and

phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze: *Phospholipase ...

-D.

In bacteria

Where phosphatidylcholine is the principal

in animals, phosphatidylethanolamine is the principal one in

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. One of the primary roles for phosphatidylethanolamine in bacterial membranes is to spread out the negative charge caused by

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

ic membrane

s. In the bacterium ''E. coli'', phosphatidylethanolamine play a role in supporting lactose permeases active transport of lactose into the cell, and may play a role in other transport systems as well. Phosphatidylethanolamine plays a role in the assembly of lactose permease and other membrane proteins. It acts as a 'chaperone' to help the membrane proteins correctly fold their tertiary structures so that they can function properly. When phosphatidylethanolamine is not present, the transport proteins have incorrect tertiary structures and do not function correctly. Phosphatidylethanolamine also enables bacterial multidrug transporters to function properly and allows the formation of intermediates that are needed for the transporters to properly open and close.

Structure

As a

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 ...

, phosphatidylethanolamine consists of a combination of

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 ...

esterified with two

fatty acids In chemistry, in particular 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, ...

and

phosphoric acid Phosphoric acid (orthophosphoric acid, monophosphoric acid or phosphoric(V) acid) is a colorless, odorless phosphorus-containing solid, and inorganic compound with the chemical formula . It is commonly encountered as an 85% aqueous solution, ...

. Whereas the phosphate group is combined with

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 ...

in phosphatidylcholine, it is combined with

in phosphatidylethanolamine. The two fatty acids may be identical or different, and are usually found in positions 1,2 (less commonly in positions 1,3).

Synthesis

The

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

pathway and the cytidine diphosphate-ethanolamine pathways are used to synthesize phosphatidylethanolamine. Phosphatidylserine decarboxylase is the enzyme that is used to decarboxylate phosphatidylserine in the first pathway. The phosphatidylserine decarboxylation pathway is the main source of synthesis for phosphatidylethanolamine in the membranes of the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

. Phosphatidylethanolamine produced in the mitochondrial membrane is also transported throughout the cell to other membranes for use. In a process that mirrors

synthesis, phosphatidylethanolamine is also made via the cytidine diphosphate-ethanolamine pathway, using

as the substrate. Through several steps taking place in both the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

and

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

, the synthesis pathway yields the end product of phosphatidylethanolamine. Phosphatidylethanolamine is also found abundantly in soy or egg lecithin and is produced commercially using chromatographic separation.

Regulation

Synthesis of phosphatidylethanolamine through the

pathway occurs rapidly in the

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

. However, phosphatidylserine is made in the

. Because of this, the transport of phosphatidylserine from the endoplasmic reticulum to the mitochondrial membrane and then to the inner mitochondrial membrane limits the rate of synthesis via this pathway. The mechanism for this transport is currently unknown but may play a role in the regulation of the rate of synthesis in this pathway.

Presence in food, health issues

Phosphatidylethanolamines in food break down to form phosphatidylethanolamine-linked Amadori products as a part of the Maillard reaction. These products accelerate

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

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 ...

peroxidation, causing

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

to cells that come in contact with them. Oxidative stress is known to cause food deterioration and several diseases. Significant levels of Amadori-phosphatidylethanolamine products have been found in a wide variety of foods such as

chocolate Chocolate is a food made from roasted and ground cocoa beans that can be a liquid, solid, or paste, either by itself or to flavoring, flavor other foods. Cocoa beans are the processed seeds of the cacao tree (''Theobroma cacao''); unprocesse ...

, soybean milk,

infant formula Infant formula, also called baby formula, simply formula (American English), formula milk, baby milk, or infant milk (British English), is a manufactured food designed and marketed for feeding to babies and infants under 12 months of age, ...

, and other

processed foods Food processing is the transformation of agricultural products into food, or of one form of food into other forms. Food processing takes many forms, from grinding grain into raw flour, home cooking, and complex industrial methods used in the mak ...

. The levels of Amadori-phosphatidylethanolamine products are higher in foods with high lipid and sugar concentrations that have high temperatures in processing. Additional studies have found that Amadori-phosphatidylethanolamine may play a role in

vascular disease Vascular disease is a class of diseases of the vessels of the circulatory system in the human body, body, including blood vessels – the arteries and veins, and the lymphatic vessels. Vascular disease is a subgroup of cardiovascular disease. Diso ...

, act as the mechanism by which

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

can increase the incidence of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

, and potentially play a role in other diseases as well. Amadori-phosphatidylethanolamine has a higher plasma

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

in diabetes patients than healthy people, indicating it may play a role in the development of the disease or be a product of the disease.

References

External links

*
Phosphatidylethanolamine
at the AOCS Lipid Library. {{Acetylcholine receptor modulators Cholinergics Phospholipids Membrane biology Phosphatidylethanolamines