Phospholipases: Degradation of Phospholipids in Membranes and Emulsions

Abstract

Abstract Phospholipases are enzymes that degrade phospholipids through hydrolytic cleavage of carboxy‐ and phospho‐diester bonds. The enzymes are classified as phospholipases A 1 , A 2 , C or D depending on the site of hydrolysis at the sn‐1 or sn‐2 acyl ester bond, at the glycerol phosphate bond or at the glycerol phosphate‐base phosphodiester bond, respectively. Phospholipases A 2 are secreted as components of snake and insect venoms, mammalian digestive juices and inflammatory exudates. Intracellular phospholipases participate in a broad spectrum of important physiological functions and pathophysiological processes through modification of phospholipids and generation of products that are potent regulators and messengers. These enzymes have evolved to hydrolyse phospholipids at an organized lipid–aqueous interface. Secreted phospholipase A 2 can serve as a prototype for interfacial catalysis. Key Concepts: Phospholipases are hydrolytic enzymes that cleave at one of the four potential cleavage sites leading to the classification as phospholipase A 1 , A 2 , C or D. These enzymes function at the interface with organized membranes and serve as models for interfacial catalysis. Hydrolytic products of catalysis depending on the specific enzyme and substrate include free fatty acids, lysosphospholipids, diacylglycerol, phosphatidic acid and phosphorylated or free base (e.g. choline, ethanolamine, serine and inositol). Secreted phospholipase A 2 is an important component of snake and insect venoms, mammalian digestive fluids and inflammatory exudates where it leads to degradation of membranes and emulsified lipids. Intracellular phospholipases have important roles in intracellular signalling through the generation of precursors of signalling molecules such as arachidonic acid, lysosphospholipids and inositol phosphates. Intracellular phospholipase A 2 activity generates the lysophospholipid substrate that is necessary for remodelling of cellular phospholipids by the deacylation–reacylation pathway. Phospholipase activity inhibitors include specific agents that act directly on the enzyme and also agents that nonspecifically act by changing the organization of the interface or interfere with interfacial binding of the protein.