Functions of Phospholipids

Phospholipids can be classified according to several schemes; however, I find it useful to think of them in terms of structural and functional categories.

Structural phospholipids comprise the majority of lipid bilayers found in eukaryotic cell membranes and organelles as well as internal membrane systems, including the endoplasmic reticulum (ER), Golgi, and nuclear envelope. 

The three most common structural phospholipids are modified versions of diacylglycerol. They are phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine.

The chemical make up of all three is similar, consisting of a hydrophilic head containing phosphate groups and a hydrophobic tail consisting of two long lipid chains, whose carbon atoms may or may not be saturated with hydrogen.

Saturated lipids (fats) have all single bonded carbons; monounsaturated fats contain one double bonded carbon atom; polyunsaturated fats contain two or more carbons with double bonds.

Other phospholipids that serve a largely structural role include cardiolipin (diphosphatidylcholine), first isolated from the mitochondrial membranes of cardiac cells but also a key component of pulmonary surfactant; and sphingosine, found in the myelin sheaths that insulate neuronal axons.    

Functional phospholipids are a diverse group of molecules that play key roles in cellular signaling. The most well understood member of this group is phosphatidylinositol (PIP2). Although it comprises less than 1% of the lipid bilayer, it is essential for the transduction of many hormonal signals. 

The general pathway is as follows:

A hormone, e.g. epinephrine, binds to the extracellular domain of a G protein coupled receptor (GPCR) such as Gq. This induces a conformational change in the GPCR, leading the alpha subunit of the G protein to dissociate, bind the high energy molecule GTP, and activate the enzyme phospholipase C (PLC). PLC cleaves phosphatidylinositol into diacylglycerol (DAG) and the short lived molcule inositol triphosphate (IP3).

DAG activates an enzyme called Protein Kinase C (PKC), which in turn phosphorylates many target proteins involved in cell metabolism and mitosis. 

DAG itself can be cleaved into arachidonic acid, a 20 carbon molecule that gives rise to the so called eicosanoids, including prostaglandins, prostacyclins, thromboxanes, and leukotrienes.

Meanwhile, IP3 binds to calcium channel receptor proteins embedded in the ER, leading to the release of calcium ions from the ER lumen. The resulting spike in cytosolic calcium can have numerous effects, including smooth muscle contraction, acid secretion from gastric parietal cells, and hormone release from many endocrine tissues. 

Another phospholipid group that has gained attention for its role in cell signaling is ceramide, a component of sphingolipids including sphingomyelin. Accumulation of ceramide can trigger apoptosis, or programmed cell death, in several types of cells. Although the mechanism is not well understood, aggregates of ceramide may form pores in mitochondrial membranes, leading to the release of cytochrome c, which in turn triggers apoptosis. 

Rounding out this discussion of functional phospholipids is a group called the plasmalogens. These phospholipids, derived from dihydroxyacetone phosphate contain an ether linkage at their C1 acyl groups. The best known plasmalogen is platelet activating factor (PAF), produced by basophils and other cells during the acute inflammatory response. PAF triggers platelet aggregation and vasodilation. The ether linkage makes PAF more water soluble than other phospholipids.