Phosphatidylcholine

Dr. Narendhirakannan RT

Assistant Professor

Department of Biochemistry

Phosphatidylcholine

Phospholipids contain fatty acids, glycerol, and phosphorous.

The phosphorous part of the phospholipid substance — the lecithin —is made up of PC.

For this reason, the terms phosphatidylcholine and lecithin are often usedinterchangeably, although they're different.

• Phosphatidylcholines (PC) are a class of phospholipids thatincorporate choline as a headgroup.

• They are a major component of biological membranes and can beeasily obtained from a variety of readily available sources, such as eggyolk or soybeans, from which they are mechanically or chemicallyextracted using hexane.

• They are also a member of the lecithin group of yellow-brownish fattysubstances occurring in animal and plant tissues. Dipalmitoylphosphatidylcholine (a.k.a. lecithin) is a major componentof pulmonary surfactant and is often used in the L/S ratio to calculatefetal lung maturity.

• While phosphatidylcholines are found in all plant and animal cells,they are absent in the membranes of most bacteria

• Phosphatidylcholine is a major constituent of cellmembranes and pulmonary surfactant, and is more commonly found inthe exoplasmic or outer leaflet of a cell membrane.

• It is thought to be transported between membranes within the cell byphosphatidylcholine transfer protein (PCTP).

• The body makes a brain chemical called acetylcholine fromphosphatidylcholine.

• Acetylcholine is important for memory and other bodily functions.

• Since phosphatidylcholine might increase acetylcholine, there is interestin using it for improving memory and for conditions such as Alzheimer'sdisease.

1. It can help boost cognitive function

2. It may aid in liver repair

3. It may help protect against medication side effects

4. It may help ease symptoms of ulcerative colitis

5. It may promote lipolysis

6. It may help dissolve gallstones

• PC helps support many of your body’s functions, ranging from fat metabolism to maintaining cell structure. You can get enough from foods such as eggs, red meat, and whole grains, and food sources are the best first choice

Phosphatidyl ethanolamine• Phosphatidylethanolamines are 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 can subsequently methylate the amine ofphosphatidylethanolamines to yield phosphatidylcholines.

• It can mainly be found in the inner (cytoplasmic) leaflet of the lipid bilayer

• Phosphatidylethanolamine or 1,2-diacyl-sn-glycero-3-phosphoethanolamine (once given the trivial name 'cephalin') is usuallythe second most abundant phospholipid in animal and plant lipids, afterphosphatidylcholine, and it is frequently the main lipid component ofmicrobial membranes.

• It can amount to 20% of liver phospholipids and as much as 45% of thoseof brain; higher proportions are found in mitochondria than in otherorganelles.

• As such, it is obviously a key building block of membrane bilayers, and it ispresent exclusively in the inner leaflet of the plasma membrane, forexample.

• It is a neutral or zwitterionic phospholipid (at least in the pH range 2 to 7)

• Phosphatidylethanolamines are found in all living cells, composing 25%of all phospholipids.

• In human physiology, they are found particularly in nervous tissue suchas the white matter of brain, nerves, neural tissue, and in spinal cord,where they make up 45% of all phospholipids

• Phosphatidylethanolamines play a role in membrane fusion and indisassembly of the contractile ring during cytokinesis in cell division.

• Additionally, it is thought that phosphatidylethanolamineregulates membrane curvature.

• Phosphatidylethanolamine is an important precursor, substrate, ordonor in several biological pathways

• In humans, metabolism of phosphatidylethanolamine is thought to beimportant in the heart.

• When blood flow to the heart is restricted, the asymmetrical distributionof phosphatidylethanolamine between membrane leaflets is disrupted,and as a result the membrane is disrupted.

• Additionally, phosphatidylethanolamine plays a role in the secretionof lipoproteins in the liver.

• This is because vesicles for secretion of very low-densitylipoproteins coming off of the Golgi have a significantly higherphosphatidylethanolamine concentration when compared to othervesicles containing very low-density lipoproteins

Phosphatidylserine

• Phosphatidylserine is a fatty substance called a phospholipid.

• It covers and protects the cells in your brain and carries messagesbetween them.

• Phosphatidylserine plays an important role in keeping your mind andmemory sharp.

• Animal studies suggest that the level of this substance in the braindecreases with age.

• Phosphatidylserine is used for Alzheimer's disease, age-relateddecline in mental function, improving thinking skills in young people,attention deficit-hyperactivity disorder (ADHD), depression,preventing exercise-induced stress, and improving athleticperformance.

• Although phosphatidylserine is distributed widely among animals, plantsand microorganisms, it is usually less than 10% of the totalphospholipids, the greatest concentration being in myelin from braintissue.

• For example, mouse brain and liver contain 14 and 3%phosphatidylserine, respectively.

• However, it may comprise 10 to 20 mol% of the total phospholipids inthe plasma membrane, where under normal conditions it isconcentrated in the inner leaflet, and in the endoplasmic reticulum ofcells.

• In the yeast S. cerevisiae, it is a minor component of most cellularorganelles other than the plasma membrane, where surprisingly it canamount to more than 30% of the total lipids.

• In most bacteria, it is a minor membrane constituent, although it isimportant as an intermediate in phosphatidylethanolaminebiosynthesis.

• Membrane location: Phosphatidylserine modulates membrane charge locally,enabling the recruitment of soluble cations and proteins, and so it contributesto the organization of processes within cell membranes.

• Its distribution within membranes is tightly controlled as it facilitates signallingwithin the various cellular compartments.

• Enzyme activation: In addition to its function as a component of cellularmembranes and as a precursor for other phospholipids, phosphatidylserine isan essential cofactor that binds to and activates a large number of proteins,especially those with signalling activities.

• The negative charge on the lipid facilitates the binding to proteins throughelectrostatic interactions or Ca2+ bridges.

• Blood coagulation: Phosphatidylserine is an important element of the bloodcoagulation process in platelets, where it is transported from the inner to theouter surface of the plasma membrane in platelets activated by exposure tofibrin-binding receptors.

• Apoptosis: In addition in response to particular calcium-dependent stimuli,phosphatidylserine is known to have an important role in the regulation ofapoptosis or programmed cell death, the natural process by which aged ordamaged cells are removed from tissues before they can exert harmful effects.

Phosphatidylinositol• Phosphatidylinositol consists of a family of lipids as illustrated on the

right, a class of the phosphatidylglycerides.

• In such molecules the isomer of the inositol group is assumed to be themyo- conformer unless otherwise stated.

• Typically phosphatidylinositols form a minor component on thecytosolic side of eukaryotic cell membranes.

• The phosphate group gives the molecules a negative charge atphysiological pH.

• The distinctive subcellular location of the different phosphoinositidespecies, together with the rapid and reversible nature ofphosphorylation, gives them a central and general position in the fieldsof cell signalling cascades and intracellular membrane trafficking.

• Phosphatidylinositol 4-phosphate is the precursor for the 4,5-bisphosphate, but it binds to a protein on the cytoskeleton of the celland has its own characteristic functions.

• It is the most widely distributed of the phosphoinositides, and inaddition to the Golgi and the plasma membrane, it is present in lateendosome, lysosomes, secretory vesicles and autophagosomes.

Sphingomyelin• Sphingomyelin or ceramide 1-phosphocholine consists of

a ceramide unit with a phosphorylcholine moiety attached to position 1of the sphingoid base component. It is thus the sphingolipid analogueof phosphatidylcholine, and like that lipid it is zwitterionic.

• Sphingomyelin is primarily of animal origin and is a ubiquitouscomponent of all animal cell membranes, from mammals to nematodes(and in a few protozoa), where it is by far the most abundantsphingolipid.

• Indeed, it can comprise as much as 50% or more of the lipids in certaintissues, though it is usually lower in concentration thanphosphatidylcholine.

• For example, it makes up about 10% of the lipids of brain, where it is akey constituent of myelin, but 70% of the phospholipids of the humanlens.

• Sphingomyelin is primarily of animal origin and is a ubiquitous component of all animalcell membranes, from mammals to nematodes (and in a few protozoa), where it is by farthe most abundant sphingolipid.

• Indeed, it can comprise as much as 50% or more of the lipids in certain tissues, though it isusually lower in concentration than phosphatidylcholine.

• For example, it makes up about 10% of the lipids of brain, where it is a key constituent ofmyelin, but 70% of the phospholipids of the human lens. Like phosphatidylcholine,sphingomyelin tends to be in greatest concentration in the plasma membrane of cells andespecially in the outer leaflet.

• Thus, all the sphingomyelin in human erythrocyte membranes is in the outer leaflet, and~90% of that in the plasma membrane of nucleated cells is in the outer leaflet.

• It is also abundant in the nucleus where it is the main phospholipid associated withchromatin.

• All lipoprotein fractions in plasma contain appreciable amounts of sphingomyelin with ahigher proportion in the VLDL/LDL. Sphingomyelin is the single most abundant lipid inerythrocytes of most ruminant animals, where it replaces phosphatidylcholine entirely.

• In this instance, there is known to be a highly active phospholipase A that breaks down theglycerophospholipids, but not sphingomyelin.

Glycolipids

• Glycolipids are lipids with a carbohydrate attached by a glycosidic(covalent) bond.

• Their role is to maintain the stability of the cell membrane and tofacilitate cellular recognition, which is crucial to the immune responseand in the connections that allow cells to connect to one another toform tissues.

• Glycolipids are found on the surface of all eukaryotic cell membranes,where they extend from the phospholipid bilayer into the extracellularenvironment

• The essential feature of a glycolipid is thepresence ofmonosaccharide or oligosaccharide boudto a lipid moiety.

• The most common lipids in cellularmembranesare glycerolipids and sphingolipids, whichhave glycerol or a sphingosine backbones,respectively.

• Fatty acids are connected to thisbackbone, so that the lipid as a whole hasa polar head and a non-polar tail.

• The lipid bilayer of the cellmembrane consists of two layers of lipids,with the inner and outer surfaces of themembrane made up of the polar headgroups, and the inner part of themembrane made up of the non-polarfatty acid tails.

Classification of glycolipids

• Glyceroglycolipids: a sub-group of glycolipids characterized by an acetylated ornon-acetylated glycerol with at least one fatty acid as the lipid complex.

• Glyceroglycolipids are often associated with photosynthetic membranes andtheir functions.

• The subcategories of glyceroglycolipids depend on the carbohydrate attached.

Galactolipids: defined by a galactose sugar attached to a glycerol lipid molecule.They are found in chloroplast membranes and are associated with photosyntheticproperties.

Sulfolipids: have a sulfur-containing functional group in the sugar moiety attachedto a lipid.

• An important group is the sulfoquinovosyl diacylglycerols which are associatedwith the sulfur cycle in plants

• Glycosphingolipids: a sub-group of glycolipids based on sphingolipids.

• Glycosphingolipids are mostly located in nervous tissue and are responsible for cell signaling.

• Cerebrosides: a group glycosphingolipids involved in nerve cell membranes.

• Galactocerebrosides: a type of cerebroseide with galactose as the saccharide moiety

• Glucocerebrosides: a type of cerebroside with glucose as the saccharide moiety; often found in non-neural tissue.

• Sulfatides: a class of glycolipids containing a sulfate group in the carbohydrate with a ceramide lipid backbone. They are involved in numerous biological functions ranging from immune response to nervous system signaling.

• Gangliosides: the most complex animal glycolipids. They contain negatively charged oligosacchrides with one or more sialic acid residues; more than 200 different gangliosides have been identified. They are most abundant in nerve cells.

• Globosides: glycosphingolipids with more than one sugar as part of the carbohydrate complex. They have a variety of functions; failure to degrade these molecules leads to Fabry disease.

• Glycophosphosphingolipids: complex glycophospholipids from fungi, yeasts, and plants, where they were originally called "phytoglycolipids". They may be as complicated a set of compounds as the negatively charged gangliosides in animals.

• Glycophosphatidylinositols: a sub-group of glycolipids defined by a phosphatidylinositol lipid moiety bound to a carbohydrate complex. They can be bound to the C-terminus of a protein and have various functions associated with the different proteins they can be bound to.

Functions• Cell–cell interactions

• The main function of glycolipids in the body is to serve as recognition sites for cell–cellinteractions.

• The saccharide of the glycolipid will bind to a specific complementary carbohydrate orto a lectin (carbohydrate-binding protein), of a neighboring cell.

• The interaction of these cell surface markers is the basis of cell recognitions, andinitiates cellular responses that contribute to activities such as regulation, growth, andapoptosis

• Immune responses• An example of how glycolipids function within the body is the interaction between

leukocytes and endothelial cells during inflammation.• Selectins, a class of lectins found on the surface of leukocytes and endothelial cells bind

to the carbohydrates attached to glycolipids to initiate the immune response.• This binding causes leukocytes to leave circulation and congregate near the site of

inflammation.• This is the initial binding mechanism, which is followed by the expression

of integrins which form stronger bonds and allow leukocytes to migrate toward the siteof inflammation.

• Glycolipids are also responsible for other responses, notably the recognition of hostcells by viruses

Cerebrosides

• Cerebrosides is the common name for a group of glycosphingolipidscalled monoglycosylceramides which are important components inanimal muscle and nerve cell membranes.

• They consist of a ceramide with a single sugar residue at the 1-hydroxylmoiety.

• The sugar residue can be either glucose or galactose; the two major typesare therefore called glucocerebrosides (a.k.a. glucosylceramides)and galactocerebrosides (a.k.a. galactosylceramides).

• Galactocerebrosides are typically found in neural tissue, whileglucocerebrosides are found in other tissues.

• A defect in the degradation of glucocerebrosides is Gaucher's disease.

• The corresponding defect for galactocerebrosides is Krabbe disease.

Gangliosides

• A ganglioside is a molecule composed of aglycosphingolipid (ceramide and oligosaccharide) with one or more sialicacids (e.g. n-acetylneuraminic acid, NANA) linked on the sugar chain.

• NeuNAc, an acetylated derivative of the carbohydrate sialic acid, makesthe head groups of gangliosides anionic at pH 7, which distinguishesthem from globosides.

• The name ganglioside was first applied by the German scientist ErnstKlenk in 1942 to lipids newly isolated from ganglion cells of the brain.

• More than 60 gangliosides are known, which differ from each othermainly in the position and number of NANA residues.

• It is a component of the cell plasma membrane that modulates cell signaltransduction events, and appears to concentrate in lipid rafts

Significance• The oligosaccharide groups on gangliosides extend well beyond the surfaces

of the cell membranes, and act as distinguishing surface markers that canserve as specific determinants in cellular recognition and cell-to-cellcommunication.

• These carbohydrate head groups also act as specific receptors forcertain pituitary glycoprotein hormones and certain bacterial protein toxinssuch as cholera toxin.

• The functions of gangliosides as specific determinants suggest its importantrole in the growth and differentiation of tissues as well as in carcinogenesis.

• It has been found that tumor formation can induce the synthesis of a newcomplement of ganglioside, and very low concentrations of a specificganglioside can induce differentiation of cultured neuronal tumor cells

• Blood types• Blood types are an example of how glycolipids on cell membranes mediate cell

interactions with the surrounding environment.

• The four main human blood types (A, B, AB, O) are determined bythe oligosaccharide attached to a specific glycolipid on the surface of red bloodcells, which acts as an antigen.

• The unmodified antigen, called the H antigen, is the characteristic of type O,and is present on red blood cells of all blood types.

• Blood type A has an N-acetylgalactosamine added as the main determiningstructure, type B has a galactose, and type AB has all three of these antigens.

• Antigens which are not present in an individual's blood will cause antibodies tobe produced, which will bind to the foreign glycolipids.

• For this reason, people with blood type AB can receive transfusions from allblood types (the universal acceptor), and people with blood type O can act asdonors to all blood types (the universal donor).