Phospholipid

Phospholipid
n., plural: phospholipids
[ˌfɒsfəˈlɪpɪd]
Definition: A lipid consisting of a glycerol bound to two fatty acids and a phosphate group.

What is a phospholipid? Phospholipids are a subgroup of lipids. Other major types of lipids are fatty acids, sphingolipids, sterol lipids, and prenol lipids. Lipids are organic compounds that are readily soluble in the nonpolar solvent (e.g. ether) but not in a polar solvent (e.g. water). Let us know more about this topic and define phospholipids.

Phospholipid Definition

A phospholipid is composed of a glycerol backbone attached on one end to two fatty acids and the other end has the esterified phosphoric acid and an organic alcoholic group. Phospholipids are basically complex lipids. Characteristically, a phospholipid molecule has a polar head group and a non-polar tail group. The fatty acid chains form the hydrophobic or lipophilic or non-polar tail whereas the esterified phosphate group forms the hydrophilic or polar head group.

Hence, the question arises. Are phospholipids hydrophobic? … or Are phospholipids hydrophilic? The presence of polar (or hydrophilic or water-loving) head group and non-polar (or hydrophobic or lipid-loving) tail impart the amphiphilic nature to these molecules.

Amphiphilic (Greek word-‘amphi’ means “both“; ‘philic’ means “loving“) molecules are those molecules that have an affinity towards both water molecules as well as lipid molecules.

Phospholipids are amphipathic or amphiphilic lipids, i.e., the non-polar fatty acid tails make phospholipid hydrophobic whereas the polar head makes phospholipid hydrophilic. (Figure 1) Being amphiphilic in nature, phospholipid molecules when exposed to water or an aqueous environment, self-assemble to form bilayer or micellar structure. Self-assembly is a characteristic feature of phospholipids.

This is because, being amphiphilic in nature, the polar or the water-loving head group tends to move towards the water molecule while the non-polar, hydrophobic tails tend to move away from the water molecules. As a result of this, the phospholipid head and tail form a micellar structure (micelles are small droplet-like structures). Thus, phospholipid in water has the capability to form micelles. Further, depending on the condition, these micelles can be single-layer lipidic spheres or bilayer lipidic spheres (which are better known as liposomes).

Interestingly, when these phospholipidic molecules are exposed to a lipidic or non-polar environment, phospholipid tails and head self-assemble in reverse fashion to form reverse-micelles, i.e., the fatty acid tails which are non-polar move towards the non-polar molecule whereas the polar head group tend to move away from the non-polar molecules resulting in the formation of reverse-micelles, i.e., phospholipids in oil form reverse micelle. (Figure 2)

In jist, we can say, phospholipid molecules act oppositely in the polar and non-polar environment. It is important to note that such self-assembly of the phospholipids occurs spontaneously.

Phospholipids are the naturally occurring molecules and a major component of all living cells. Phospholipids are the building blocks of all the biological membranes that play a plethora of cell organelle functions and cellular functions. Because of its amphiphilic nature, the phospholipid membrane has a characteristic bilayer structure in the cellular membranes.

Let us now understand, what is the function of phospholipids in the cell membrane?
Phospholipids are important components of cellular membranes, such as the plasma membrane. The basic component of the cellular membrane is phospholipid proteins and cholesterol, of which phospholipids are the major components.

Membrane phospholipids provide membrane fluidity and flexibility because of which the cell can perform the function, like endocytosis. Moreover, the phospholipid functions to impart selective permeability to the membrane, and hence they control the movement of molecules across the cell membrane.

Examples and Types of Phospholipids

What are phospholipid examples? The plasma membrane is made up of phospholipid along with cholesterol and proteins. The most common phospholipids are phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin.

One may wonder, where are phospholipids found? Well, the phospholipid is the main component of the cell membrane of all the plant cells as well as animal cells. Milk, soy, egg yolk, and marine phospholipids are the important source of dietary phospholipids or lecithin phosphatidylcholine. Lecithin is a phospholipid. Phospholipids in milk are sphingolipids and glycerophospholipids.

There are certain phospholipids wherein the glycerol backbone is replaced by long-chain amino-alcohol sphingosine, such phospholipids are known as sphingophospholipids. Sphingomyelin is the most common example of sphingophospholipid. Sphingomyelin is found in neuronal and brain tissues. Sphingomyelin is an example of choline phospholipids.

Thus, based upon the backbone, types of phospholipids are:

• Glycerophospholipids (or phosphoglycerides), or glycerol phospholipids wherein backbone is glycerol
• Sphingophospholipids, wherein the backbone is sphingosine

The phosphate may further be bound to other molecules, such as hydrogen, choline, serine, ethanolamine, inositol...

Thus, it is the hydrophilic component that may help determine the type of a phospholipid.

For example:

• If bound to hydrogen: phosphatidic acid
• If bound to choline: phosphatidylcholine
• If bound to serine: phosphatidylserine
• If bound to ethanolamine: phosphatidylethanolamine
• If bound to inositol: phosphatidylinositol

Each of these phospholipids goes through a particular biosynthetic pathway. The phosphatidic acid is the most fundamental of these phospholipids as it serves as the precursor to many phospholipids. The biosynthesis of phospholipids usually starts at Gro3P.

Properties of Phospholipids

Here are the common properties of phospholipids:

• Amphiphilic in nature
• Have the capability to self-assemble
• Weak hydrophobic interactions hold the lipid bilayer formed due to self-assembly
• The membrane formed by the phospholipids, i.e., the membrane phospholipids, has the capability to restrict the movement of molecules across the lipid bilayer.
• Phospholipids are the building blocks of the cellular membrane and anchor the membrane proteins in it.
• The phospholipids impart membrane fluidity and flexibility as a result of which cellular processes, like pinocytosis and endocytosis, can occur.

Phospholipid Structure

Let us know to understand the basic structure of phospholipid, this will enable us to have a clear idea about how many fatty acids are in a phospholipid or how many phosphate groups are present in the phospholipid molecule…

The phospholipid molecule primarily has a glycerol backbone. The glycerol present in the backbone possesses three-carbon positions namely, sn1, sn2, and sn3. (Figure 5)

At the positions, sn 1 and sn2, the fatty acid chains of any carbon length and saturation are esterified with the glycerol backbone. The carbon chain length of the fatty acids usually varies from 14 to 24 carbon atoms).

Interestingly, one of the fatty chains possesses a higher number of unsaturated or cis bonds which results in the formation of a small kink in the tail portion of the fatty acid chain of phospholipids. This fatty acid chain is the unsaturated phospholipid component. On the other hand, the second fatty acid chain of the phospholipids usually does not have any unsaturated bond and has a completely saturated carbon chain. This difference in the two fatty acid chains is essential and provides the necessary membrane fluidity and flexibility to the phospholipidic membrane structure. In summary, the phospholipid fatty acids are of two types, one is saturated while the other is unsaturated. 

At the sn3 position of the glycerol, the phosphoric acid molecule gets attached to the glycerol via esterification. This phosphoric acid molecule is further esterified with an organic alcoholic group. (Figures 6)

Depending upon the alcoholic group attached to the phosphate group of phospholipids, different types of phospholipids are available, e.g., phosphatidylinositol or inositol phospholipid, phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, or phosphatidylethanolamine. Consequently, depending upon the polar head group and the pH of the media, the phospholipids can also form zwitterions (molecules with both positive and negative charges).

A change in pH can result in the formation of a charged polar head resulting in charged phospholipids. Depending upon the charge acquired, phospholipids can be anionic phospholipids (e.g., phosphatidylserine) or cationic phospholipids (e.g., distearolyphosphatidycholine or DSPC).

Functions of Phospholipids

Here are the various biological functions of phospholipids:

• Phospholipids are one of the primary components of the cell membranes. The phospholipid membrane or lipid bilayer is selectively permeable and thus regulates the entry and exit of material/molecules in the cell.
• Phospholipids impart cellular membrane fluidity and flexibility.
• Phospholipids also help in cellular signal transduction.
• Phospholipids are essential for the availability of polyunsaturated n-3 fatty acids, like docosahexaenoic acid (DHA), for the brain and nervous system. Thus, phospholipids are critical for the normal functioning of the nervous system. Cephalin phospholipid is found in the brain, specifically in the white matter of the brain.
• Dipalmitoylphosphatidylcholine or DPPC surfactant is the phospholipid found in the lungs. It is a very essential phospholipid that helps in reducing surface tension and preventing alveolar collapse while expiration phenomena. Surfactant phospholipid mixture is also administered to prematurely born newborn babies in order to open up the lungs for respiration.
• Phospholipids along with cholesterol are important membrane components. The cholesterol:phospholipid ratio controls the immunological functioning of the lymphocytes. With the age, the amount of cholesterol increases, and thus, changes the cholesterol:phospholipid ratio, this affects the immunological functioning of the lymphocytes.
• High intake of alcohol results in a reduction in the number of phospholipids in the hepatic or liver cells. This leads to reduced flexibility of the hepatic cell membrane eventually leading to liver injury. Reports suggest that the administration of phospholipids helps to recover from hepatic cell damage.
• Cell polarity is maintained with the help of the phospholipid-binding capacity of polarity regulators of the cell.
• One of the endogenous phospholipids is plasmalogens those functions as antioxidant protecting organs from oxidative stress. These antioxidant phospholipids also help in the significant reduction of oxidized phospholipids in the cell.
• Phospholipids are essential for lipid metabolism and absorption.
• Dietary supplementation of phospholipids is reported to inhibit prostaglandin synthesis and thus exert an anti-inflammatory effect.
• Phospholipids are widely used as a drug delivery vehicle in the pharmaceutical industry. One of the most commonly explored pharmaceutical dosage form for the delivery of anti-cancer drugs is liposomes. Liposomes are primarily made up of phospholipids (e.g., hydrogenated soy phosphatidylcholine, hydrogenated egg pc or egg phosphatidylcholine, soy lecithin, egg lecithin, etc) and have a unique bilayer spherical structure due to characteristic feature of self-assembly of phospholipids. Further, phospholipids, like egg-phosphatidylcholine, soy-phosphatidylcholine, and lecithin are widely used as emulsifiers in the pharmaceutical formulation development.
• Phospholipids are very good drug solubilizers, as they are amphiphilic in nature. Hence, In the pharmaceutical industry, for solubilization of poorly soluble drugs, phospholipids are used.
• Phospholipids in plants function in the control of the growth of plants and in the management of stress.

Phospholipids of Biological Membranes: a closer look

Phospholipids are amphipathic compounds in a way that the ‘head’ is hydrophilic and the lipophilic ‘tail’ is hydrophobic. This is essential in the formation of a lipid bilayer feature of biological membranes. Being amphipathic, the phospholipid tails tend to avoid interacting with water. In contrast, the phospholipid heads may interact with water. Thus, when placed in water or an aqueous solution, the phospholipids tend to aggregate by orienting their tails towards each other. Thus, the ‘heads’ tend to face the water or the aqueous solution. As a result, the phospholipid component of biological membranes enables its distinctive “lipid bilayer”. The phospholipid tails line up internally while the phospholipid heads are on both sides facing the exterior. The phospholipids in biological membranes are prevented from packing together by the presence of sterols (another group of lipids).

Phospholipids serve as a major structural component of most biological membranes, e.g. cell membranes. The phospholipids are vital to the function of the cell membrane. Being amphipathic, their presence creates an effective barrier preventing the entry of all molecules. Not all molecules would be able to enter the cell. Only those that are small enough (e.g. oxygen and carbon dioxide) and those that are non-polar can be allowed passage across the lipid bilayer. Other molecules (especially polar molecules) would need carriers or transport systems in order to enter the cell through the cell membrane.

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Further Reading

• lipid
• plasma membrane

References

• Drescher, S., & van Hoogevest, P. (2020). The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery. Pharmaceutics, 12(12), 1235. https://doi.org/10.3390/pharmaceutics12121235
• Henneberry, A. L., Wright, M. M., & McMaster, C. R. (2002). The major sites of cellular phospholipid synthesis and molecular determinants of Fatty Acid and lipid head group specificity. Molecular biology of the cell, 13(9), 3148–3161. https://doi.org/10.1091/mbc.01-11-0540
• Küllenberg, D., Taylor, L. A., Schneider, M., & Massing, U. (2012). Health effects of dietary phospholipids. Lipids in health and disease, 11, 3. https://doi.org/10.1186/1476-511X-11-3
• Wang, B., & Tontonoz, P. (2019). Phospholipid Remodeling in Physiology and Disease. Annual review of physiology, 81, 165–188. https://doi.org/10.1146/annurev-physiol-020518-114444

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