What are Phospholipids?

Phospholipids refer to lipid compounds containing phosphate groups. They are an important part of lipids and have unique biological activities and play a vital role in maintaining normal life activities of the body. Phospholipids are amphipathic molecules, with a hydrophilic nitrogen- or phosphorus-containing group at one end and a hydrophobic (lipophilic) long hydrocarbon chain at the other end. It is precisely because of this characteristic that the hydrophilic ends of phospholipid molecules are close to each other and the hydrophobic ends are close to each other. They often form a phospholipid bilayer with other molecules such as proteins and cholesterol, which is the structure of the cell membrane.

Fig. 1. Phospholipid chemical structure.

As an important structural component of biological cell membranes, phospholipids participate in the digestion, absorption and transportation of lipids. At the same time, they are also one of the basic substances for life activities and an important substance for metabolism and signal transmission of living organisms. In addition, phospholipidomics is a branch of lipidomics, which mainly conducts comprehensive qualitative and quantitative analysis and research on phospholipid molecules in organisms. It can reflect the overall change process of phospholipids in the organism. By studying the differences in phospholipid metabolism in the organism, it can screen out potential biomarkers, discover disease mechanisms, and ultimately make targeted diagnosis and treatment of metabolic diseases.

Phospholipid Definition

Phospholipids are not only an important component of biological membranes, but also play an important role in the absorption and transport of fats and the storage of fatty acids, especially unsaturated fatty acids. About 95% of the lipids in the mitochondrial membrane are phospholipids, and about 20% of the phospholipids in the inner mitochondrial membrane are cardiolipin. Phospholipids are also important components of plasma lipoproteins and are regulators of biological membrane enzyme systems. In addition to the human body's own ability to synthesize phospholipids, it can also obtain a certain amount of phospholipids from food every day. Food rich in phospholipids include egg yolks, lean meat, brain, liver, kidney and other animal offal. In particular, egg yolk contains the most lecithin, reaching 9.4%. In addition to animal foods, soybeans are the richest plant food, with a phospholipid content of up to 1.5% to 3%. Other plant seeds such as sunflower seeds, flax seeds, sesame seeds, etc. also contain certain amounts. It has good effects in protecting cell membranes, delaying aging, lowering blood lipids, and preventing and treating fatty liver.

Phospholipid Structure

Phospholipids are lipids containing carbon, hydrogen, oxygen, and phosphate. The structure consists of a glycerol backbone esterified with fatty acid chains at positions 1 and 2, while the phosphate group at position 3 is further esterified with a polar moiety (alcohol). The polar head group confers hydrophilicity, while the attached fatty acid chain confers hydrophobicity (non-polar region) to the phospholipid molecule. Therefore, phospholipids are amphipathic. Four different functional groups attached to the second carbon of the glycerol moiety give the phospholipid molecule chirality. Variations in attached polar head groups, backbones, and fatty acid side chains result in different properties.

Phosphoglycerides

Phosphoglycerides have a glycerol-3-phosphate backbone, with the other two hydroxyl groups of the glycerol molecule esterified by fatty acids. Various phosphoglycerides can be formed by esterifying the phosphate group with different structurally diverse small molecules. The most abundant phospholipids in the body include phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin), phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), and phosphatidylinositol, each with several variations depending on the fatty acids they contain. Glycerophospholipids can be divided into many types due to different substituent groups, among which the important ones are:

1) Choline + phosphatidic acid → phosphatidylcholine, also known as lecithin

2) Ethanolamine + phosphatidic acid → phosphatidylethanolamine, also known as cephalin

3) Serine + phosphatidic acid → phosphatidylserine

4) Glycerol + phosphatidic acid → phosphatidylglycerol

5) Inositol + phosphatidic acid → phosphatidylinositol

6) Cardiolipin is composed of C1 and C3 of glycerol combined with two molecules of phosphatidic acid. It is an important component of the inner mitochondrial membrane and bacterial membrane, and is the only phospholipid molecule with antigenicity.

7) In addition to the above 6 types, in the glycerophospholipid molecule, the fatty acyl group at the first position of glycerol is replaced by a long-chain alcohol to form an ether, such as plasmalogen and platelet activating factor (PAF), which all belong to phosphoglycerides.

Fig. 2. Chemical structure of phosphoglycerides.

Sphingomyelin

Sphingomyelin is a type of phospholipid containing sphingosine or dihydrosphingosine, lacking glycerol in its structure. It is a molecule where a fatty acid is linked to sphingosine via an amide bond, with sphingosine or dihydrosphingosine consisting of a hydrophobic tail composed of a long-chain hydrocarbon and a polar head composed of two hydroxyl groups and an amino group. Sphingomyelin contains phosphoric acid, with the end alkyl substituent group being phosphatidylcholine. The most abundant sphingomyelin in the human body is sphingomyelin, composed of sphingosine, fatty acids, and phosphatidylcholine. Sphingomyelin is an important phospholipid that constitutes biological membranes, often coexisting with phosphatidylcholine on the outer surface of cell membranes. Sphingolipids can be divided into two types according to the substituent group X:

1) X is phosphocholine called sphingomyelin

2) X is a sugar group called glycosphingolipid

Phospholipid Bilayer

The phospholipid bilayer is a well-known structural assembly of phospholipids. Its nonpolar tail stretches inwards to form a continuous internal hydrocarbon core, while the polar head faces outside the cell, extending into the aqueous phase. Phospholipid bilayers and monolayers play important roles in nature as components of cell membranes and lipoproteins. In cell membranes, the phospholipid bilayer forms a permeable barrier between water compartments. The structure of the phospholipid bilayer is soft and easy to bend and flow, and they account for 20% to 80% of the membrane weight depending on the type of membrane. In addition to their structural interface roles, aggregated phospholipids also modulate the function of associated proteins and enzymes through direct binding and physical effects. Therefore, synthetic phospholipid bilayers in the form of multilamellar or small bilamellar vesicles have emerged as a model to study the structural and dynamic properties of natural phospholipid aggregates. For example, liposomes are spherical phospholipid bilayers with a size of 50 to 500 nm that can encapsulate water-soluble and insoluble drugs and proteins in their hydrophilic core or bilayer, respectively.

Fig. 3. Phospholipid bilayer diagram.

Phospholipid Molecule

BOC Sciences is a leading lipid supplier, offering a wide range of high-quality products to meet the diverse needs of researchers and industry. We have established a strong supply chain with extensive capabilities in the procurement, synthesis, purification and characterization of phospholipids. We also offer a full range of mPEG Phospholipids such as DSPE PEG(2000)-N-Cy5, DOPE-PEG-Azide ammonium salt, DSPE-PEG(1000) Carboxylic Acid, and DOPE-PEG-COOH sodium salt. We adhere to strict quality control standards and regulatory guidelines to ensure product safety and reliability. In addition, we have lipid manufacturing capabilities that comply with Good Manufacturing Practice (GMP) and International Organization for Standardization (ISO) standards.

Phospholipid Function

Phospholipids are essential compounds containing phospholipid roots and are fundamental to life. Cell membranes are composed of approximately 40% proteins and 50% lipids (mainly phospholipids). They consist of phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and others, each playing specific roles in different parts and organs of the human body. Phospholipids play a significant role in activating cells, maintaining metabolism, regulating hormone secretion, enhancing immunity and regeneration, and more. Additionally, phospholipids promote fat metabolism, prevent fatty liver, lower serum cholesterol, improve blood circulation, and prevent cardiovascular diseases.

Emulsification

Phospholipids can break down high levels of blood lipids and cholesterol, cleanse the blood vessels, and facilitate smooth blood circulation, earning them the title of "blood vessel scavengers." They emulsify neutral fats and cholesterol deposits in the blood vessels into harmless particles that dissolve in water and are excreted from the body. This process also prevents excess fat from depositing on the blood vessel walls, reducing pressure on the cardiovascular system. The powerful emulsification properties of phospholipids are fundamental in preventing and treating modern civilization diseases. For instance, in cardiovascular diseases, excessive consumption of meat leads to cholesterol and lipid deposits on blood vessel walls, causing narrowed blood vessels and hypertension. The emulsification effect of phospholipids can emulsify cholesterol and lipids deposited on the blood vessel walls, facilitating their removal from the body and preventing blockages that lead to conditions like coronary heart disease and blockages.

Proliferation

Nerve cells and brain cells in the human body are enveloped by phospholipid-made cell membranes. Insufficient phospholipids can damage these membranes, leading to cognitive decline and mental stress. The acetyl group contained in phospholipids combines with choline in the intercellular space, forming acetylcholine. Acetylcholine serves as a signaling molecule for transmitting information between various nerve cells and brain cells, speeding up information transmission, enhancing memory, and preventing dementia.

Cell activation

Phospholipids are crucial components of cell membranes responsible for substance exchange inside and outside the cells. Without an adequate daily intake of phospholipids, cells can become malnourished and lose vitality. While the liver can synthesize some phospholipids, most are obtained from the diet, especially after the age of thirty to forty. The effectiveness of phospholipids is highest around 25 degrees Celsius, and their activity diminishes significantly at temperatures exceeding 50 degrees Celsius. Therefore, it is advisable for both healthy and sub-healthy individuals to consume phospholipids as a way to maintain health and well-being.

Anti-inflammatory

Dietary supplementation of phospholipids can treat inflammatory diseases and regulate inflammatory responses. In mouse models, soy PC was shown to be effective in reducing the inflammatory response of arthritis and similar inflammatory processes. Phospholipids have been shown to improve the pharmacokinetics of some drugs, including NSAIDs, and increase the anti-inflammatory and analgesic activity of NSAIDs in acute and chronic arthritis models.

Anti-cancer

Phospholipids play an important role in inhibiting tumors and metastasis. The cell membrane of cancer cells has special characteristics. The tumor cell membrane with the ability to metastasize loses the adhesion properties of normal cells, causing the cancer cells to separate from the surrounding (tumor) tissue and migrate to other tissues or organs, leading to tumor metastasis. Modulating lipid raft composition and density could potentially alter cancer cell activity and metastatic behavior.

Regulate blood lipids/reduce the risk of cardiovascular disease

The association of oral dietary phospholipid supplements with lipid profile and cardiovascular risk has been extensively studied. Relevant studies have reported that soybean lecithin has a significant lowering effect on total cholesterol in patients with primary hyperlipidemia and can also prevent platelet aggregation. Therefore, combined therapy with lipid-lowering drugs and phospholipids while controlling platelet function may be a more effective approach to treat hypercholesterolemia.

Regulate neurodevelopment

Age-related memory impairment is a progressive, physiologically normal deterioration of memory function that affects nearly everyone. It is known that the lipid composition of brain cells changes with age. The content of n-3 series polyunsaturated fatty acids (3-PUFA) in the brain decreases with age, membrane fluidity decreases, and choline activity decreases, requiring the stimulation of PC and PUFAs and the release of neurotransmitters. Some researchers believe that the decline in memory and learning ability in the elderly is the result of the reduction of PC and PUFAs in brain tissue. Phospholipids have also been proven to be important and effective carriers of PUFAs.

Regulate immunity

Cholesterol/phospholipids (C/PL) in cell membranes increase with age. Changes in the composition of cell membranes have an impact on their properties and functions. For example, in lymphocytes, an increase in the C/PL ratio reduces their immune function. Studies have shown that lymphocyte membrane viscosity can be modulated by restoring an optimal C/PL ratio. Increasing the content of phospholipids in lymphocyte cell membranes is expected to restore immune function in the elderly.

What are the Uses of Phospholipids?

It has been demonstrated that several phospholipids, including phosphatidylserine and phosphatidylcholine, have anti-inflammatory and neuroprotective effects. They can control inflammatory mediator production and lessen inflammation in a variety of illnesses, such as arthritis and inflammatory bowel disease. Moreover, phospholipids are important for both the prevention and treatment of neurodegenerative illnesses including Parkinson's and Alzheimer's. The solubility, stability, delivery, and targeting of drugs are all improved by phospholipids, which also contribute significantly to the effectiveness and safety of therapeutic formulations.

• Drug delivery system: Phospholipids are used to develop liposomal drug delivery systems. Liposomes are spherical vesicles composed of a phospholipid bilayer that can encapsulate drugs within their aqueous core or lipid bilayer. These liposomes can improve drug stability, enhance drug solubility, extend drug circulation time, and target specific tissues or cells.
• Drug solubilization: Phospholipids can solubilize hydrophobic drugs that are difficult to dissolve in water. By forming micelles or mixed micelles with phospholipids, these drugs can be incorporated into lipid bilayers and enhance their solubility and bioavailability.
• Membrane permeability studies: Phospholipid bilayers are used to simulate cell membranes to study drug permeability and absorption. By incorporating phospholipids into artificial membrane models, researchers can assess the ability of drugs to cross cell membranes and predict their bioavailability.
• Drug targeting and controlled release: Phospholipids can be modified to bind targeting ligands, such as antibodies or peptides, on their surface. This allows specific drug delivery to target tissues or cells. Furthermore, phospholipids can be engineered to respond to external stimuli (e.g. pH, temperature) and release drugs in a controlled manner, thereby enhancing therapeutic efficacy and reducing side effects.
• Drug Stability and Protection: Phospholipids can protect drugs from degradation by providing a physical barrier against environmental factors such as light, heat or enzymes. They also prevent drug aggregation and improve drug stability during storage and transportation.

Phospholipid Synthesis

Synthetic phospholipids can be divided into semi-synthetic phospholipids and fully synthetic phospholipids based on different starting materials.

Semi-synthetic phospholipids mainly include hydrogenated soybean phospholipids and hydrogenated egg yolk phospholipids. Among them, hydrogenated soybean lecithin has fewer types of fatty acids, so it is more stable after hydrogenation, so its application is more extensive. Another reason is that the cost of soy lecithin is also cheaper. Therefore, soybean lecithin is generally used as raw material for hydrogenation reaction.

According to the structural composition of phospholipids, the idea of fully synthetic phospholipids can be deduced, that is, 1 molecule of glycerol, 1 molecule of phosphate ester, and 2 molecules of fatty acids can be used to obtain high-purity fully synthetic phospholipids. For example, the synthesis route of DPPC can be designed as follows. The finished product of DPPC can be obtained by reacting 1 molecule of glycerophosphatidylcholine and 2 molecules of palmitic acid through reaction, filtration, purification, crystallization, drying, etc. And the purity of DPPC can be as high as more than 99%. In addition, the fatty acids here can be customized, so a variety of phospholipids with controllable phase transition temperatures can be obtained. For example, by customizing various fatty acids and bases, various phospholipids such as DPPC, PSPC, and DPPE can be obtained through synthetic means.

BOC Sciences can provide a variety of custom synthesis services to researchers, pharmaceutical companies and other industries that require high-quality phospholipids.