A phospholipase is a member of a very complex group of enzymes that break down phospholipids into fatty acids and other compounds. Phospholipids contain fatty acids, a phosphate group, and frequently a diglyceride group. This is a compound with two glycerol groups. Phospholipids are components of all membranes in cells.
There are a number of different classes of phospholipases. Even within the same class, the enzymes can have very different sequence similarities and modes of regulation. Their products are often signaling molecules that relay instructions to the cell to initiate or terminate reactions. Their activities are tightly regulated because of this.
Phospholipases are defined by the enzymatic reaction they catalyze. The classes are phospholipase A, which has members A1 and A2; phospholipase B, which can carry out the reactions of both A1 and A2; phospholipase C; and phospholipase D. Phospholipase is usually abbreviated as PL.
Among the most well-studied classes is PLA2, which is a large group of enzymes of unrelated protein families. PLA2 is defined by its release of a fatty acid from the second carbon group of glycerol. Some PLA2s remain inside the cell and are known as cytosolic PLs, or cPLA2. They translocate to membranes when the calcium level rises. A large number of PLA2s are secreted outside of the cell.
An example of the secreted type is pancreatic PLA2. This is the major PL in pancreatic secretion. It catalyzes the hydrolysis of phospholipids in the diet so nutrients can be digested.
Other types of secreted PLA2s can have very different functions. One type provides protection against bacteria in human tears. Another type of PLA2 generates free fatty acids for the outermost layer of the skin.
Both cPLA2s and some of the secreted PLA2s can generate the fatty acid arachidonic acid from membrane phospholipids. This is a 20 carbon polyunsaturated fatty acid. Once it has been liberated from the phospholipids, it can be oxygenated to generate eicosanoids. These compounds can affect many potentially pathogenic responses. For example, the hormone group prostaglandins are types of eicosanoids and can cause inflammation.
Inhibitors of PLA2s can have clinical applications. The role of the secreted PLA2s in lipid metabolism can have effects on human diseases. Increased levels of these enzymes have been correlated with coronary artery disease. Novel inhibitors have been developed that show promise in treating patients with this disorder. Inhibitors of brain PLA2 have been proposed to treat neurological disorders.
There are a number of receptors identified for PLA2s. Receptors are proteins that specifically and tightly bind a particular molecule and transmit a signal. Some reptile and invertebrate venoms are toxic secreted PLA2s. It is thought that they manifest their toxicity by binding to the mammalian PLA2 receptors.
The PLC family is another group that is highly studied for its roles in mammalian physiology, particularly in causing cellular signaling. PLCs are only found intracellularly, or inside of cells. These enzymes cleave phospholipids before the phosphate group, generating diacylglycerol, DAG, and inositol triphosphate, IP3. IP3 diffuses into the cytoplasm and causes calcium levels to rise there. This generates an array of changes in cellular metabolism.
The combined activities of DAG and calcium from PLC activate protein kinase C. This is a key family of regulatory enzymes that adds a phosphate group to a number of proteins. Protein kinase C activity is involved in the regulation of normal cell growth. It has also been implicated in tumor development. The development of inhibitors to PLC is an active area of research.
The secretion of PLs is also thought to be a strategy used by bacteria, parasites, and pathogenic fungi to infect their host. Several different types of PLs have been implicated in pathogenicity. They include PLA1, PLA2, and PLB.
