Phospholipid

An amphiphile (from the Greek αμφις, amphis: both and φιλíα, philia: love, friendship; also termed "amphipathic") is a term describing a chemical compound possessing both hydrophilic (water-loving, polar) and lipophilic (fat-loving, non-polar) properties; lipophilic properties can also be considered hydrophobic (water-avoiding). The phospholipid head usually contains a negatively charged phosphate group and glycerol; it is hydrophilic. The phospholipid tails usually consist of 2 long fatty acid chains; they are hydrophobic and avoid interactions with water. When placed in aqueous solutions, phospholipids are driven by hydrophobic interactions that result in the fatty acid tails aggregating to minimize interactions with water molecules. These specific properties allow phospholipids to play an important role in the phospholipid bilayer. In biological systems, the phospholipids often occur with other molecules (e.g., proteins, glycolipids, sterols) in a bilayer such as a cell membrane.[2] Lipid bilayers occur when hydrophobic tails line up against one another, forming a membrane of hydrophilic heads on both sides facing the water.

Such movement can be described by the fluid mosaic model, that 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 However, this model has now been superseded, as through the study of lipid polymorphism it is now known that the behaviour of lipids under physiological (and other) conditions is not simple.

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 properties. The ethosomal formulation of ketoconazole using phospholipids is a promising option for transdermal delivery in fungal infections.[3]

Computational simulations of phospholipids are often performed using molecular dynamics with force fields such as GROMOS, CHARMM, or AMBER.

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

Phospholipid synthesis occurs in the cytosolic side of ER membrane [7] 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.[8][9]

Common sources of industrially produced phospholipids are soya, rapeseed, sunflower, chicken eggs, bovine milk, fish eggs etc. 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.

Some types of phospholipid can be split to produce products that function as second messengers in signal transduction. 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 neurons[10] to leukocyte signal pathways started by chemokine receptors.[11]

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, a plant hormone similar in structure to prostaglandins that mediates defensive responses against pathogens.

Phospholipids can act as emulsifiers, 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 soybeans, 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.

See table below for an extensive list.

• Natural phospholipid derivates:

  egg PC (Egg lecithin), 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, funcitionalized-phospholipid, terminal activated-phospholipid)

• Cable theory
• Galactolipid
• Sulfolipid
• Hydrophile