Phospholipids: Function & Diseases

Phospholipids are instrumental in building cell membranes. They represent complex lipids that contain a phosphoric ester linkage. They are also amphiphilic because they have a hydrophilic and a lipophilic domain.

What are phospholipids?

Phospholipids are glycerol or sphingosine esters, each containing two fatty acid molecules and a phosphoric acid residue, which in turn may be esterified with various alcohols. They are the basic building blocks of cell membranes and cell organelles. There they form a double lipid layer that separates the intracellular space from the extracellular space. Both spaces have aqueous environments whose molecules do not come into contact with each other. The phospholipid molecules each contain a hydrophilic and a lipophilic region. The hydrophilic region is represented by the glycerol and the phosphate group, and additionally often by the alcohol esterified at the phosphate group. The lipophilic region is located at the fatty acid residues. The lipophilic groups are deposited together, while the hydrophilic groups are averted from each other. Thereby, the lipid bilayer contains two hydrophilic layers each, which delimit the cell to the outside and to the inside. Within the bilayer lies the lipophilic region. The phospholipids are divided into phosphoglycerides and sphingomyelins. Furthermore, the phosphoric acid residues can be esterified with choline, ethanolamine or with serine, among others. In the case of phosphoglycerides, this results in phosphatidylcholines (lecithin), phosphatidylethanolamines, or phosphatidylserines.

Function, action, and roles

Phospholipids represent the main component of biomembranes. In this function, they separate the cell interior from the surrounding space. Simultaneous hydrophilicity and lipophilicity enable phospholipids to mediate between water and oil as a boundary layer. Thus, lipophilic substances attach to the lipophilic end of the molecule. Polar substances and aqueous solutions bind in the hydrophilic region. Both water, water-soluble compounds and water-insoluble but fat-soluble compounds are brought into solution at the same time. In water, phospholipids always form bilayers with their hydrophilic molecule portions facing toward the water and their lipophilic molecule portions facing away from the water. At the same time, the membranes form spaces within which biochemical reactions can take place undisturbed by external influences. The nonpolar regions of the phospholipids contribute to their fluidity. Although the nonpolar fatty acid residues cluster together, the molecular interactions here are weak due to the nonpolarity. Thus, the hydrocarbon tails can easily shift with respect to each other. The hydrophilic heads are indeed averse to each other. However, stronger binding forces for polar molecules are present there. The lipophilic character of the cell membrane separates two aqueous environments from each other, so that biochemical reactions can proceed undisturbed in both areas. With the help of transport proteins, molecules or ions can be selectively transported through the channels built into the double membrane layer. Receptors present within the double membrane transmit signals to the interior of the cell. Vesicles can separate from the phospholipid membrane, which can take up substances foreign to the cell or release enzymes or hormones into the extracellular space. Furthermore, in addition to its function as a membrane building block, lecithin also serves as a starting material for the formation of the neurotransmitters acetylcholine and norepinephrine. It also plays an important role in the context of fat digestion.

Formation, occurrence, properties, and optimal values

Phospholipids present in membranes are phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingolipids. In addition, cholesterol and its derivatives provide membrane fluidity. The lipids facing the cell surface may be glycosylated. The synthesis of phospholipids takes place in the smooth endoplasmic reticulum. From there, the molecules are transported to their destination in the form of vesicles and incorporated into the membrane. In the human body, phospholipids are particularly abundant in the brain, bone marrow, liver or heart, in addition to their normal occurrence in every cell membrane. Foods particularly rich in phospholipids are egg yolks, seeds, roots, tubers, mushrooms, yeast and vegetable oils.

Diseases and disorders

In connection with phospholipids, the so-called antiphospholipid syndrome is known. This disorder occurs mainly in women and is characterized by increased incidence of arterial and venous thrombosis. As a result, heart attacks, strokes, pulmonary embolisms or thromboses often occur. Paradoxical bleeding occurs in the skin, resulting in increased consumption of platelets. Miscarriages often occur. The cause of this disease is an autoimmune disorder. The immune system is directed against certain phospholipids such as cardiolipin or prothrombin. However, these are always antibodies against the phospholipid-associated proteins. The syndrome occurs both alone and in the context of various autoimmune diseases, which belong to the rheumatic group. The most common underlying disease is systemic lupus erythematosus (SLE). However, antiphospholipid syndrome can also occur in the context of malignant tumors or HIV. Secondary antiphospholipid syndrome may also occur in rheumatoid arthritis, lupus erythematosus or Sjögren’s syndrome. An important role in the pathogenesis of the disease is played by the protein beta-2-glycoprotein I. It is present as a monomer in the blood and binds, among other things, to the cell membrane of monocytes and platelets, whereupon the platelets are activated. When it binds to the cell membrane, the molecule undergoes conformational changes that make it vulnerable to attack by specific antibodies. This results in the formation of a dimer that can bind to various receptors located in the membrane. As a result, thrombus formation is activated. There is also a special form of the disease that particularly affects young men from the second to the fourth decade of life. This is the rare Hughes-Stovin syndrome with similar symptoms.