Phospholipases: Degradation of Phospholipids in Membranes and Emulsions

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.

Adaptation of Phaeobacter inhibensDSM 17395 to growth with complex nutrients

“…Considering that phospholipids most likely occur in aggregates (e.g. membrane debris of lysed cells), activity of phospholipases is thought to require close contact between the outer membrane of the growing cell and the membrane debris . Phospholipases initiate degradation of phospholipids by extracellular hydrolytic cleavage into glycerol‐3‐phosphate and two fatty acids.…”

Peroxiredoxin 6: A Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2Activities

“…All PLA 2 enzymes function to hydrolyze an acyl or alkyl linkage at the sn-2 position of phospholipids. The secreted enzymes utilize a His-Asp dyad as the catalytic center, whereas the other members of the family are serine based, either as a Ser-Asp dyad or Ser-Asp-His catalytic triad (23). This triad is similar to that found in many proteases as well as lipolytic enzymes (66).…”

Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling

“…The motif in Prdx6 that is responsible for phospholipid hydrolysis is 32 S- 140 D- 26 H [78], a catalytic triad that is commonly found in lipases and proteases [81,82]. This triad is present in all mammalian Prdx6 proteins for which the amino acid sequence has been determined and those examined have all shown PLA 2 activity [28].…”