The importance of phospholipase-A2 in prostaglandin biosynthesis

Role of Prostaglandins and Arachidonic Acid Derivatives in the Coupling of Cerebral Blood Flow to Cerebral Metabolism

“…Eleva tion of free arachidonic acid levels also occurs with cerebral trauma, seizures, and electroshock (Bazan , 1970(Bazan , , 1971. Phospholipase A2 may be the rate limiting step in the formation of prostaglandins by controlling the supply of the precurser, arachidonic ac id (Flower and Blackwell, 1976). Unfortunately, the study of cerebral prostaglandin synthesis has been complicated by the fact that conversion of ex ogenous arachidonic acid by brain is less than 2% whether a homogenate or microsomal fraction is used (Coceani, 1974;Pace-Asciak and Nashat, 1976).…”

“…The rate-limiting step for any of these pathways appears to be the provision of the substrate-arachidonic acid-by the phospholipase reaction (Flower and Blackwell, 1976). The intra cellular concentration of arachidonic acid is nor mally very low-prostaglandin synthetase is a microsomal enzyme.…”

PHOSPHOLIPASE A2 ACTIVITY OF GUINEA‐PIG ISOLATED PERFUSED LUNGS: STIMULATION, AND INHIBITION BY ANTI‐INFLAMMATORY STEROIDS

“…This 'lipid pool' must therefore comprise neutral lipid esters of arachidonic acid (mono-di-or tri-glycerides or cholesterol esters), or else the phospholipid store. It is on this last possibility that most attention has been focussed and the phosphatide pool has been implicated as the source of substrate for prostaglandin biosynthesis in several tissues (Haye, et al, 1973;Flower & Blackwell, 1976;Blackwell, Duncombe, Flower, Parsons & Vane, 1977). Given that this idea is true, then the enzyme phospholipase would be implicated in the release mechanism.…”

Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells

“…The fact that ANXA1 inhibits the activity of cytosolic phospholipase A 2 (cPLA 2 ; 3) could be a clue for a better understanding of the function of ANXA1 in cell growth regulation, because cPLA 2 is an initiator enzyme of the arachidonic acid cascade and thus plays a critical role in the regulation of growth of many different types of cells (9,10). Inhibition of cPLA 2 activity is thought to be because of direct binding of ANXA1 to cPLA 2 (11,12) rather than to sequestering of substrate phospholipids by the binding of ANXA1 to them (13,14).…”