Phospholipases are enzymes that break down phospholipids into fatty acids and other compounds, and are components of all cell membranes. There are several classes of phospholipases, including phospholipase A, B, C, and D. Among the most studied classes is PLA2, which releases a fatty acid from the second carbon group of glycerol. PLA2 inhibitors may have clinical applications, and increased levels of these enzymes have been correlated with coronary heart disease. The PLC family cleaves phospholipids before the phosphate group, generating diacylglycerol and inositol triphosphate, which cause an increase in calcium levels and activate protein kinase C. PL secretion is also used by pathogenic bacteria, parasites, and fungi to infect their host.
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 often a diglyceride group. This is a compound with two glycerol groups. Phospholipids are components of all membranes in cells.
There are several classes of phospholipases. Even within the same class, enzymes can have very different sequence similarities and modes of regulation. Their products are often signaling molecules that pass instructions to the cell to start or stop reactions. Their activities are strictly regulated for this reason.
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 studied classes is PLA2, which is a large group of enzymes from unrelated protein families. PLA2 is defined by the release of a fatty acid from the second carbon group of glycerol. Some PLA2 remains inside the cell and is known as cytosolic PL or cPLA2. They move to membranes when the calcium level rises. A large number of PLA2 is secreted outside the cell.
An example of the secreted type is pancreatic PLA2. This is the major PL in pancreatic secretion. Catalyzes the hydrolysis of dietary phospholipids so that nutrients can be digested.
Other types of secreted PLA2 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 skin.
Both cPLA2 and some of the secreted PLA2 can generate arachidonic fatty acid from membrane phospholipids. This is a 20-carbon polyunsaturated fatty acid. Once freed from phospholipids, it can be oxygenated to generate eicosanoids. These compounds can influence many potentially pathogenic responses. For example, the hormone group prostaglandins are types of eicosanoids and can cause inflammation.
PLA2 inhibitors may have clinical applications. The role of secreted PLA2 in lipid metabolism may have effects on human disease. Increased levels of these enzymes have been correlated with coronary heart disease. New inhibitors have been developed that show promise in treating patients with this disorder. Brain PLA2 inhibitors have been proposed to treat neurological disorders.
There are a number of identified receptors for PLA2. Receptors are proteins that specifically and tightly bind a particular molecule and transmit a signal. Some reptile and invertebrate venoms are secreted toxic PLA2. They are thought to manifest their toxicity by binding to mammalian PLA2 receptors.
The PLC family is another highly studied group for their roles in mammalian physiology, particularly in causing cell signaling. PLCs are found only intracellularly or within cells. These enzymes cleave phospholipids before the phosphate group, generating diacylglycerol, DAG, and inositol triphosphate, IP3. IP3 diffuses into the cytoplasm and causes an increase in calcium levels. This generates a series 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 PLC inhibitors is an active research area.
PL secretion is also thought to be a strategy used by pathogenic bacteria, parasites, and fungi to infect their host. Several types of PL have been implicated in pathogenicity. They include PLA1, PLA2 and PLB.
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