New insights on mammalian phospholipase A ₂ (s); comparison of arachidonoyl‐selective and ‐nonselective enzymes

Abstract

With the recent discoveries of novel forms of phospholipases A2 (PLA2s),2 new schemes for the roles of various PLA2s in lipid metabolism must be considered. The type II 14-kDa PLA2 isolated from human synovial fluid or platelet has many of the biochemical characteristics of the homologous snake venom and mammalian pancreatic PLA2s. It appears to function both as a cell-associated enzyme and extracellularly, where its expression and/or release is regulated by a variety of mediators such as cytokines or growth factors. The mammalian 85-kDa PLA2 purified from monocytic cells or platelets has no sequence homology to the 14-kDa PLA2 and exhibits biochemically different characteristics. It translocates from cytosol to particulate cell fractions in the presence of submicromolar levels of Ca2+ and has a substrate preference for sn-2-arachidonoyl-containing phospholipids. The cellular function and relative importance of these two enzymes in lipid metabolism remain to be determined. In this review, the biochemistry, localization, function, and regulation of these two distinct mammalian Ca(2+)-dependent PLA2 are compared.

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

“…They play a central role in diverse cellular processes including phospholipid digestion and metabolism, host defence, and signal transduction by catalysing the hydrolysis of the sn-2 fatty acyl bond of many different phospholipids which may themselves serve as intracellular second messengers or can be further metabolised as precursors in the production of specific proinflammatory lipid mediators such as leukotrienes, prostaglandins and hydroxyecosatetraenoic acids (HETES) via arachidonic acid (AA) formation (Fig. 4) [123]. Mammalian leukocytes contain several types of PLA 2 enzymes, the type most commonly involved in arachidonic acid production being high-molecular-mass (85 kDa) cytosolic PLA 2 (cPLA 2 ) [10,11] which requires micromolar concentrations of Ca 2+ for translocation from the cytosol to the nuclear envelope [44,45,47,63,123].…”

“…4) [123]. Mammalian leukocytes contain several types of PLA 2 enzymes, the type most commonly involved in arachidonic acid production being high-molecular-mass (85 kDa) cytosolic PLA 2 (cPLA 2 ) [10,11] which requires micromolar concentrations of Ca 2+ for translocation from the cytosol to the nuclear envelope [44,45,47,63,123]. The cPLA 2 activity seems to be regulated by G proteins and by protein kinase C [79,90].…”

Increased renal and vascular cytosolic phospholipase A2activity in rats with cirrhosis and ascites

“…8 Multiple isoforms of PLA 2 have been described that differ in their substrate specificity, Ca 2ϩ dependency, and subcellular localization. 12,13 The present study was undertaken to measure the activity of PLA 2 in kidney and aortic tissue from cirrhotic rats with carbon tetrachloride-induced cirrhosis and ascites.…”

Haemodialysis activates phospholipase A2 enzyme

“…PLA 2 enzymes characterized so far are classified into group I, II, III and IV based on their primary and secondary structure [26,27]. PLA 2 enzymes purified from human platelets and from human synovial fluid are classified under group II and are considered to account for inflammatory reactions, whereas the group I from pancreas appears not to be involved in inflammation [28][29][30].…”

“…PLA 2 enzymes purified from human platelets and from human synovial fluid are classified under group II and are considered to account for inflammatory reactions, whereas the group I from pancreas appears not to be involved in inflammation [28][29][30]. Group III enzyme has not been detected in mammalians and the function of cytosolic PLA 2 (Group IV) is not very well defined yet [27]. Inflammatory human synovial fluid PLA 2 (group II) is resistant to low pH, optimally active in the presence ofmM concentrations of calcium and at basic pH [31,32].…”