Dipalmitoylphosphatidylcholine
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3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.018.322 |
PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C40H80NO8P | |
| Molar mass | 734.053 g·mol−1 |
| Surface tension: | |
| 4.6 ± 0.5 x 10−10 M[1] | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two palmitic acids attached to a phosphatidylcholine head-group.
It is the main constituent of pulmonary surfactants, which reduces the work of breathing and prevents alveolar collapse during breathing. It also plays an important role in the study of liposomes and human bilayers.
A single time-point "snapshot" of a molecular dynamics simulation of DPPC lipid bilayer formation in a two phase system.[clarification needed][citation needed]
DPPC and lung surfactant
Lung surfactant (LS) is a surface active material produced by most air-breathing animals with the aim of reducing the surface tension of water when gas exchange occurs, given that the inhalation and exhalation movements may cause damage if there is not enough energy to sustain it.
The monolayer formed by the LS on the interface is composed mainly by phospholipids (80%), proteins (12%) and neutral lipids (8%). Among these phospholipids, the prevailing is phosphatidylcholine (PC, or lecithin) (70 – 85%), which composes a pool where 50% of the material is DPPC.
DPPC by its own does already have the capacity to minimize the tension, but it requires the presence of proteins and other lipids from the surfactant to ease the adsorption in the air-liquid interphase.
The fact that DPPC is a variant of the lecithin and its structure based on an hydrophilic head and hydrophobic tails grants it such properties. The polar and hidrophilic head is caused by the choline radical, oriented towards the alveolar liquid, and the non-polar and hydrophobic tails are due to the palmitic acid chains, oriented towards the outer side.
Synthesis of DPPC
The synthesis of phospholipids from pulmonary surfactant takes place in the endoplasmic reticulum of type II pneumocytes. Pulmonary surfactant has a protein and a lipid composition. Specifically, we found that phosphatidylcholine is the most abundant phospholipid (70%-85%) and it mostly disaturates in the form of dipalmitoylphosphatidylcholine (DPPC).
The novo synthesis of phosphatidylcholine in the lung occurs mainly from the formation of CDP-choline. The passage from CDP-choline to phosphatidylcholine is catalyzed by Choline-phosphate cytidyltransferase. Although the main enzyme acting on its synthesis is Choline-phosphate cytidyltransferase, there are certain conditions under which the enzymes choline kinase, glycerol-3-phosphate acyltransferase and phosphatidate phosphatase may play a regulatory role.
From the novo biosynthesis, we obtain 45% of the total DPPC of the pulmonary surfactant. The rest is formed by disacylation and reacylation mechanisms from unsaturated acyl chains of phosphatidileolin. The elimination of the acyl chain is produced by transacylation, thus obtaining a lysophospholipid. After the disacylation or transacylation process, we obtain lysophosphatidylcholine, which results in DPPC after reacillating it with palinitoilCoa by means of aciltransferated lysophosphatidylcholine.
Characteristics
Its relation with temperature
This phospholipid is found in a solid/gel phase at 37ºC (at the effective temperature of the human body). Its melting point is around 41.3ºC. So, when the temperature is above 41ºC, DPPC is no longer found in a gel phase but in a liquid one.
Effects of temperature in DPPC bilayers
DPPC bilayers have been demonstrated to have different properties depending on the temperature when studied in contact with silica surfaces.
Layer thickness remains the same at 25ºC and at 39ºC, while when the temperature is further increased to 55ºC, the DPPC bilayer structure modifies in a significant way which causes the layer thickness to decrease. The reason of this trait is that, in fact, at 55ºC DPPC is found in a liquid disordered state, whereas at a lower temperature it is found in a gel state.
Indeed, temperature affects the layer roughness as well, which starts to change slightly when temperature is lowered to 25ºC.
Finally, it is demonstrated that the load bearing capacity of this bilayer is higher when the temperature overtakes the phase transition temperature (due to its increased fluidity). When this molecule is found in a liquid state, which the fluidity is much larger, it is thought that the bilayer develops a certain self-healing capacity[2].
Amphipathic behaviour
DPPC is an amphipathic lipid. This characteristic is due to its hydrophilic head, composed by the phosphatidylcholine group, and its hydrophobic tail, composed by two palmitic acids. This trait allows DPPC to easily form micelles, monolayers, bilayers and liposomes spontaneously in contact with a polar solvent.
Its work as a surfactant
DPPC is the main phospholipid composant of pulmonary surfactant and it is surface active thanks to its amphipathic behaviour and its adsorption capacity. However, DPPC adsorption is not quite effective at the human body temperature, because at 37ºC it is found in a gel phase. So, it is required the presence of some unsaturated phospholipids (such as dioleoylphosphatidylcholine or phosphatidylglycerol) and cholesterol in surfactant to help making it more fluid, so it adsorbs more efficiently. So, when this mixture contacts with water (for example), it cumulates in the interphase water/air, causing a significant diminution of water surface tension. A thin superficial pellicule of surfactant creates in the interphase, the molecules composing the surfactant (DPPC) feel atracted by the liquid molecules (in this case H20 molecules) which causes the diminution of surface tension.
Current uses
Research uses
Commonly, DPPC is highly used for research purposes. It is mainly used to create liposomes and bilayers which are involved in bigger studies. The Langmuir-Blodgett technique allows the synthesis of liposomal DPPC bilayers. Currently, this liposomes are used in the study of the properties of this phosphatidilcoline and the mechanism of drug delivery in the human body.
Furthermore, the fact that the dynamics of vesicle fusion are different for lipids in the gel phase compared with the fluid phase, allows scientists to use DPPC along with DOPC in Atomic Force Microscopy and Atomic Force Spectroscopy.
Pharmaceutical uses
DPPc is routinely used in formulation of some medicines mainly used for the treatment of RDS in newborn infants. Currently, the drugs in which it is used are still in development as the technique which they are given. Current synthetic surfactants are combinations of DPPC, other phospholipids, neutral lipids and lipoproteins.
The appearance of the treatment of respiratory distress syndrome with surfactants it's originated in the 1960s. The firts treatment administered to some newborns with RDS was with surfactant phospholipids, specifically with dipalmitoylphosphatidylcholine by means of an aerosol (Robillard, 1964). This treatment proved to be infective, as the administration of DPPC alone did not achieve any beneficial effect. Subsequently, various studies were carried out to obtain more efficient drugs for the treatment of this disease.
Pulmonary surfactants can be classified into three types:
First, we have the first generation of protein-free synthetic surfactants. This first generation contained only DPPC. The best known was colfosceril palmitate.
Secondly, we have the second generation of natural surfactants of animal origin. It is obtained from the lungs of cattle or pigs. The surfactants bovine extracts were Infasurf and Alvofact, from porcine extracts were Curosurf and from modified bovine extracts were Survanta. Unlike the first generation newborns with RDS had less oxygen requirement and ventilatory support within 72 hours of drug administration.
Third, we have the third generation of synthetic peptides or recombinant proteins. These use a mixture of different components. DPPC is used as an agent to drecrease surface tension and the rest of the aggregates increase adsorption. The best known are Venicute and Surfaxin. They are still under development so we don't know what are the advantages over the second generation.
In summary, DPPC is used in formulation of some therapeutical pulmonary surfactants like Survanta and Beraksurf in order to standardize the content of drug.[3] Also is used for liposome formation in order to delivery of drug in the body.[4]
Surfactant Disfunction Disorder is a disease that affects new born children where pulmonary surfactant is insufficient for adequate breathing causing respiratory distress syndrome.
Despite DPPC being one of the major components of lung surfactant, most of the genetic errors that are linked with surfactant disfunction disorder are not linked to DPPC. The main causes of this disease are differences in the production surfactant proteins B and C due to genetic conditions.
However, there is a genetic condition that is related to DPPC which is a deficiency in the production of ABCA1 protein which is crucial in the transportation of phospholipids and therefore DPPC to the lamellar bodies of the alveolar cells where DPPC interacts with surfactant proteins to form surfactant.
Current studies cannot find a correlation between the percentage of DPPC in lung surfactant with the age of gestation although there is a proven correlation between the percentage of DPPC and POPc in babies with respiratory distress syndrome compared with babies without this condition. Theese correlations suggests that a particular surfactant composition will lead to respiratory distress syndrome, irrespective of gestational age.
The correlation between DPPC percentage and respiratory distress syndrome is why DPPC is used to make drugs to treat newborn infants with the desease.
See also
References
- ^ Smith, Ross; Tanford, Charles (June 1972). "The critical micelle concentration of l-α-dipalmitoylphosphatidylcholine in water and water/methanol solutions". Journal of Molecular Biology. 67 (1): 75–83. doi:10.1016/0022-2836(72)90387-7. PMID 5042465.
- ^ Wang, Min; Zander, Thomas; Liu, Xiaoyan; Liu, Chao; Raj, Akanksha; Florian Wieland, D. C.; Garamus, Vasil M.; Willumeit-Römer, Regine; Claesson, Per Martin; Dėdinaitė, Andra (2015-05-01). "The effect of temperature on supported dipalmitoylphosphatidylcholine (DPPC) bilayers: Structure and lubrication performance". Journal of Colloid and Interface Science. 445: 84–92. doi:10.1016/j.jcis.2014.12.042. ISSN 0021-9797.
- ^ "Surfactant - Medical Countermeasures Database".
- ^ Li, Jing; Wang, Xuling; Zhang, Ting; Wang, Chunling; Huang, Zhenjun; Luo, Xiang; Deng, Yihui (2015). "A review on phospholipids and their main applications in drug delivery systems". Asian Journal of Pharmaceutical Sciences. 10 (2): 81–98. doi:10.1016/j.ajps.2014.09.004.