Classification of phospholipids based on their internal composition (alcohol active group)
Glycerophospholipids are phospholipids with a glycerol backbone, comprised of glycerol-3-phosphate esterification at the C1 and C2 positions. There are six different subtypes of glycerophospholipids, including phosphatidic acid, lecithin (phosphatidylcholine), cephalin (phosphatidylethanolamine), phosphatidylinositol, phosphatidylserine, and cardiopoline (diphosphatidylglycerol).3
Phosphatidic acid is the smallest and most basic glycerol phospholipid. It has a strong anion that provides a negative charge density to the membrane. Phosphatidic acid is a synthetic phospholipid with several possible derivatives (Table 1), which can be synthesized according to the required application.4
Table 1Phospholipids used in liposomal formulations along with the chemical name and structure4
Phospholipid | Structure and chemical name |
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Phosphatidic acid | 1,2-Dioleoyl-sn-glycero-3-phosphate (DOPA) | 1,2-Dilauroyl-sn-glycero-3-phosphate (DLPA) |
| 1,2-Dimyristoyl-sn-glycero-3-phosphate (DMPA) | 1,2-Distearoyl-sn-glycero-3-phosphate (DSPA) |
| 1,2-Dipalmitoyl-sn-glycero-3-phosphate (DPPA) | |
Lecithin | 1,2-Didecanoyl-sn-glycero3-phosphocholine (DDPC) | 1,2-Dierucoyl-sn-glycero-3-phosphocholine (DEPC) |
| 1,2-Dilinoleoyl-sn-glycero3-phosphocholine (DLOPC) | 1,2-Dilauroyl-sn-glycero-3-phosphocholine (DLPC) |
| 1,2-Dimyristoyl-sn-glycero3-phosphocholine (DMPC) | 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) |
| 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) | 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) |
| 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) | 1,2-Dierucoyl-sn-glycero-3-phosphocholine (DEPC) |
Cephalin (phosphatidyl ethanolamine) | 1,2-Dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE) | 1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) |
| 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) | 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) |
| 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) | 1,2-Dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE) |
| 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) | |
Cardiolipin | 1,2-Dierucoyl-sn-glycero-3[phospho-rac-(1-glycerol) (DEPG) | 1,2-Dilauroyl-sn-glycero-3[phospho-rac-(1-glycerol) (ammonium salt) (DLPG-NH4) |
| 1,2-Dimyristoyl-sn-glycero-3[phospho-rac-(1-glycerol) (DMPG) | 1,2-Dioleoyl-sn-glycero-3[phospho-rac-(1-glycerol) (DOPG) |
| 1,2-Dipalmitoyl-sn-glycero-3[phospho-rac-(1-glycerol) (ammonium salt) (DPPG-NH4) | 1,2-Distearoyl-sn-glycero-3[phospho-rac-(1-glycerol) (ammonium salt) (DSPG-NH4) |
| 1-Palmitoyl-2-oleoyl-sn-glycero-3[phospho-rac-(1-glycerol) (POPG) | |
Phosphatidyl serine (PS) | 1,2-Dilauroyl-sn-glycero-3-phosphoserine (DLPS) | 1,2-Dimyristoyl-sn-glycero-3-phosphoserine (DMPS) |
| 1,2-Dioleoyl-sn-glycero-3-phosphoserine (DOPS) | 1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (DPPS) |
| 1,2-Distearoyl-sn-glycero-3-phosphoserine (DSPS) | |
Lecithin is an egg yolk-derived natural choline-based phospholipid. It is a zwitterionic molecule, consisting of partial positive and negative charges. This phospholipid has a major influence on membrane properties such as “fluidity.” There are two types of lecithin: dipalmitoyl lecithin and lysolecithin. The structures and chemical names of several lecithin derivatives synthesized according to their applications are depicted in Table 1.
The naming of cephalins was derived from the word cephalic, meaning “related to the head.” The polar head group of cephalins is highly reactive and small in size; therefore, this type of compound has a low hydration rate. Cephalins are synthesized by adding cytidine diphosphate ethanolamine to diglyceride. Cephalins can be treated with ethanolamine, which consists of a reactive nitrogen base, to further synthesize several other derivatives for varied applications. Several derivatives of cephalins are as follows: 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine.
Phosphatidylinositol is synthesized by the reaction between the isomeric form of myo-inositol and phosphatidic acid. Inositol is present in all types of tissues as well as in cells and has a saturated fatty acid chain. Phosphatidylinositol is anionic in nature.
Phosphatidylserine is a synthetic phospholipid. Serine is anionic in nature, and derivatives of phosphatidylserine include the following: 1,2-dilauroyl-sn-glycero-3-phosphoserine, 1,2-dimyristoyl-sn-glycero-3-phosphoserine, 1,2-dioleoyl-sn-glycero-3-phosphoserine, 1,2-dipalmitoyl-sn-glycero-3-phosphoserine, and 1,2-distearoyl-sn-glycero-3-phosphoserine.
Cardiolipin contains two molecules of phosphatidic glycerol. It consists of two optically active carbons and also has a number of unsaturated fatty acid chains. Several derivatives of cardiolipin are as follow: 1,2-dierucoyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-dilauroyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-dilauroyl-sn-glycero-3 [phospho-rac-(1-glycerol)] (ammonium salt)], 1,2-dimyristoyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-dimyristoyl-sn-glycero-3 [phospho-rac-(1-glycerol)] (ammonium salt)], 1,2-dioleoyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-dipalmitoyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-dipalmitoyl-sn-glycero-3 [phospho-rac-(1-glycerol)] (ammonium salt), 1,2-distearoyl-sn-glycero-3 [phospho-rac-(1-glycerol)], 1,2-distearoyl-sn-glycero-3 [phospho-rac-(1-glycerol) (ammonium salt)], and 1-palmitoyl-2-oleoyl-sn-glycero-3 [phospho-rac-(1-glycerol)].
Chemically, sphingomyelins are N-acyl sphingosine-1-phosphatidylcholine. The backbone of sphingomyelins is sphingosine. Each molecule of sphingomyelin consists of an acyl chain. Generally, naturally obtained sphingosines contain 20 or more acyl groups. Therefore, the structure of sphingomyelin molecules is asymmetric. The phase-transition temperature of sphingomyelins ranges from 30°C to 45°C.
Classification of phospholipids based on its origin source
Natural phospholipids are obtained from natural sources like wheat germ, flax seed, sunflower, soybeans, egg yolk, and milk. Meanwhile, synthetic or semisynthetic phospholipids are tailor made, chemically synthesised phospholipids. Some examples of synthetic phospholipids are 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, dipalmitoylphosphatidylcholine, 1,2-dilauroyl-sn-glycero-3-phosphocholine, dimyristoylphosphatidylglycerol, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, sodium salt, etc.
Classification of phospholipids based on the fatty acid chain saturation
Saturated chain fatty acids exhibit comparatively more chemical stability against oxidation and hydrolysis. Some examples of saturated fatty acids include 1,2-dimyristoyl-sn-glycero-3-phosphate, 1,2-dipalmitoyl-sn-glycero-3-phosphate, 1,2-distearoyl-sn-glycero-3-phosphate, 1,2-dilauroyl-sn-glycero-3-phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine, etc.
Unsaturated chain fatty acids are more prone to oxidation and hydrolysis. Some examples of unsaturated fatty acids are; 1,2-dierucoyl-sn-glycero-3-phosphocholine, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dierucoyl-sn-glycero-3-phosphocholine, etc.