Snake Venom Phospholipase A₂ Enzymes in Cell Biology

Abstract

Phospholipase A₂ (PLA₂) (EC 3.1.1.4) enzymes are esterolytic hydrolases which catalyze the hydrolysis of 3-sn- phosphoglycerides. They specifically hydrolyze and release fatty acids from the second position (Fig. 1). These enzymes are ubiquitos in nature, and they occur as both intracellular (cellular type or cPLA₂ enzymes) and extracellular (secretory type or sPLA₂) forms. In general, cPLA₂ enzymes are found in small quantities , and hence their purification is relatively difficult. sPLA₂ enzymes, on the other hand, are found in larger quantities in nature, and snake venoms and mammalian pancreas are particularly rich sources of these enzymes. Since purification of sPLA₂ enzymes is easier, several hundreds of these enzymes play important roles in the maintenance of the cellular phospholipid pools and membrane repair through deacylation/reacylation pathways (verheij et al., 1981; Waite, 1987: Dennis et al., 1991; Kudo et al., 1993; Dennis, 1994) and biosynthesis of prostaglandins and leukotrienes. They have crucial roles in various physiological and pathological processes (Glaser et al., 1993; Dennis, 1994; Mukherjee et al, 1994). The importance of PLA₂ enzymes in fertilization (Fry et al., 1992), cell proliferation (Arita et al., 1991), smooth muscle contraction (Vadas and Pruzanski, 1986; Nakajima et al 1992; Sommers et al., 1992), and hypersensitization and chronic imflammatory diseases (Vadas and Pruzanski, 1986; Vadas et al., 1993) have been recognized.