Effect of diacylglycerols on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2.
The effects of a series of diacylglycerols (DAGs) with varying acyl chain lengths and degree of unsaturation on the activity of cobra venom, bee venom, and pig pancreatic phospholipases A2 (PL-A2S) were studied using two lipid substrates: dipalmitoylphosphatidylcholine (DPPC) or bovine liver phosphatidylcholine (BL-PC). The activities of the phospholipases critically depended on the chain length and degree of unsaturation of the added DAGs and on the chemical composition of the substrate. The effects of DAGs on cobra or bee venom PL-A2S were similar, but significantly different from the pig pancreatic PL-A2. The data, taken together with our previous NMR studies on physicochemical effects of these DAGs on lipid bilayer structure [De Boeck, H., & Zidovetzki, R. (1989) Biochemistry 28, 7439; (1992) Biochemistry 31, 623], allowed detailed correlation of the type of a bilayer perturbation induced by DAG with the activation or inhibition of the phospholipase on the same system. In general, the activation of the phospholipases correlated with the DAG-induced defects of the lipid bilayer structure. The results, however, argue against general designation of DAGs as "activators" or "inhibitors" of PL-A2S. Thus, for example, diolein activated phospholipases with the BL-PC lipid substrate, but inhibited them with the DPPC substrate. Dihexanoylglycerol and dioctanoylglycerol inhibited pig pancreatic PL-A2 with both lipid substrates and inhibited cobra or been venom PL-A2 with the DPPC substrate, but activated the latter two enzymes with the BL-PC substrate. Longer-chain DAGs (C greater than 12), which induce lateral phase separation of the bilayers into the regions of different fluidities, activated all PL-A2S with both lipid substrates.(ABSTRACT TRUNCATED AT 250 WORDS)
Zidovetzki
R
R
Department of Biology, University of California, Riverside 92521.
Laptalo
L
L
Crawford
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D001514:Bee Venoms / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology*; D004546:Elapid Venoms / Q000378:metabolism*; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology*; D010713:Phosphatidylcholines; D010741:Phospholipases A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
D001514:Bee Venoms; D004075:Diglycerides; D004546:Elapid Venoms; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; D010741:Phospholipases A