Structural and Functional Properties of Mammalian Group III Cytosolic Phospholipases A₂

Abstract

Phospholipases A₂, enzymes which hydrolyze the sn-2 fatty acyl ester bond of phosphoglycerides, are found in all mammalian cells and tissues¹. They have been subdivided into two groups: group I enzymes are derived from proenzymes and secreted. These extracellular enzymes have been characterized in great detail functionally and structurally, the best known mammalian enzyme being the pancreatic phospholipase A₂. Group II enzymes are structurally related to the group I enzymes. They have the same molecular weight of about 12 to 18 kD and show a high degree of sequence homology, but also typical differences such as a lacking cysteine residue in position 11, which is typical for group I enzymes. Group II phospholipases A₂ are found intracellularly, often membrane bound, and are secreted upon activation of the cells. Functionally they seem to play an important role in inflammations and other disease states^2,3. It has now become evident that there is a third group of calcium-dependent phospholipases A₂ distinct from the ones mentioned above. These enzymes are rather labile when purified and therefore not yet well characterized. They have been described in most detail in platelets, mesangial cells, macrophages and monocytic cell lines. The present paper will discuss some of the properties of these group III enzymes (cytosolic phospholipases A₂) and will focus on the phospholipase A₂ from the monocytic cell line THP1.