Secreted phospholipases enzymes

The exocrine pancreas secretes phospholipase A2 in an inactive zymogen form, prophospholipase A2. The enzyme is activated in the intestinal lumen by proteolytic cleavage by trypsin. Pancreatic lipase, however, is secreted in its active form, and only needs to bind colipase and substrate to be active. 

In order to carry out PHA production from triglycerides, the cells need to hydrolyze the triglycerides into free fatty acids that can be transported into the cells. For this, the cells need to secrete an enzyme called lipase. A wide variety of organisms is known to secrete lipolytic enzymes, mainly for lipid metabolism and signal transduction. Lipolytic enzymes can be classified into different classes, including lipases, esterases, and phospholipases (Arpigny and Jaeger 1999). Esterases are enzymes that hydrolyze ester bonds of soluble or partially soluble molecules. 

Murakami M, Taketomi Y, Girard C, Yamamoto K, Lambeau G (2010) Emerging roles of secreted phospholipase A2 enzymes lessons from transgenic and knockout mice. Biochimie 92 561 582... 

Cystic fibrosis can obstruct pancreatic ducts due to mucous plugging and impaired secretion of pancreatic enzymes such as lipase and phospholipases, which decreases hydrolysis and uptake oftri-acylglycerols. 

LTC4 and LTD4 are potent bronchoconstrictors and are recognized as the primary components of the slow-reacting substance of anaphylaxis (SRS-A) that is secreted in asthma and anaphylaxis. There are four current approaches to antileukotriene drug development 5-LOX enzyme inhibitors, leukotriene-receptor antagonists, inhibitors of FLAP, and phospholipase A2 inhibitors. 

I various subcellular locations within eukaryotic cells. Some of these enzymes are specific for particular polar head-groups others are nonspecific. Phospholipase A2 is a major component of snake venom (cobra and rattlesnake) and is partially involved in the deadly effects of these venoms. Because of the high concentration of phospholipase A2 in these venoms, this enzyme has been studied intensively. The pancreas is also rich in phospholipase A2, which is secreted into the intestine for digestion of dietary phospholipids. 

Phospholipase A2 catalyzes the hydrolysis of the 2-acyl linkage of all phospholipids. It is secreted as a zymogen by the pancreas, and converted to the active enzyme via a specific tryptic cleavage of the Arg-Ala link which removes an N-terminal heptapeptide from the proenzyme. Phospholipase A2 is one example of the way in which the metabolism of phospholipids is sensitive to calcium at several key points. 

Lipases are enzymes that hydrolyse triglycerides in fats and phospholipases, as the name indicates, hydrolyse phospholipids. Lipases remove long-chain fatty acids from triglycerides, and they are also frequently described as having esterase activity. There are also specific esterases described in the GI tract, for example, carboxylesterase that is secreted by the pancreas. These enzymes are included in the discussion because their activity may be relevant to the use of macromolecular materials in novel formulations, particularly for oral peptide and nucleic acid delivery. 

Scorpionid secretions represent a mixture of neurotoxic polypeptide toxins, proteolytic and hemolytic enzymes (phospholipases A, acetylcholinesterases, ribonucleases, hyaluronidases), and biogenic amines (serotonin, tryptamine, histamine). The polypeptide toxins (the so-called scorpamines) contain fewer than 40 or 60-76 mostly alkaline and aromatic amino acids stabilized by four disulfide bridges.20 96... 

Among the outer membrane enzymes, OmpT is a special protease that has been implicated in the pathogenicity of bacteria. It is monomeric with the active center pointing to the outside (Vandeputte-Rutten et al., 2001). Another enzyme, the phospholipase A OmpLA, produces holes in the outer membrane when it is activated. The activation process has not yet been clarified, but it is known to require a dimerization of OmpLA in the membrane. The activation by dimer formation has been verified by a crystal structure analysis of an OmpLA dimer that was produced by a reaction with an inhibitor (Snijder et al., 1999). It showed that each active center contained a catalytic triad Ser-His-Asn on one subunit and an ox-anion hole formed by an amide together with a hydrated Ca2+ ion on the other. The active centers are well placed for deacylating lipopolysaccha-rides of the external leaflet of the outer bacterial membrane. OmpLA functions in the secretion of colicins and virulence factors. 

In a recent study, a serine-phospholipid-selective phospholipase A has been purified and cloned its cDNA from rat platelets, which secrete two types of phospholipases upon stimulation (71). The purified enzyme from extracellular medium of activated rat platelets, yielded a 55-kDa protein band on SDS-polyacrylamide gel electrophoresis. The presence of active serine residues was confirmed by labeling the 55-kDa protein with pHJDiisopropyl fluorophosphate, an inhibitor of the enzyme. Based on cDNA for the enzyme cloned from a rat megakaryocyte cDNA library, the 456-amino acid... 

Signal transduction events encotipiss processes that are triggered by the initial interaction of agonists with specific receptors on platelets and result in the activation of effectors, such as pho holipase C and phospholipase A2, leading ultimately to discernible end re nses such as aggregation and secretion. The link between the surface receptors and the effector enzymes is provided in many instances by G-proteins. If the key conqwnents of platelet signal transduction mechanisms are the surfece receptors, the G-proteins that modulate the intracellular effectors, and the effectors, evidence now exists for specific platelet abnormalities at each of tiiese levels. 

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