Comparison of enzymatic and pharmacological activities of lysine-49 and aspartate-49 phospholipases A2 from XXXX piscivorus snake venom.

@entity18384 @entity18115 @entity2434 @entity1370 @entity3633 @entity460 @entity299 @entity2574
The basic Lys-49 phospholipase A2 (PLA2) from @entity18384 piscivorus venom is homologous to the basic @entity2574 -49 PLA2 from the same venom as well as other snake venom PLA2 enzymes. It differs, however, in several respects, most important being replacement of the previously invariant @entity2574 -49 at the @entity460 binding site by Lys, resulting in a reversed order of addition of @entity460 and phospholipid, phospholipid binding first. Although the preferences for phospholipid substrates of the two enzymes are identical, the apparent Vmax of the Lys-49 PLA2 was only 1.4 to 3% that of the @entity2574 -49 enzyme. Similarly, the Lys-49 PLA2, compared to the @entity2574 -49 PLA2 had less than 3% of the intraventricular lethal potency and 4% of the anticoagulant activity. The intravenous lethal potency of the Lys-49 enzyme was 20% that of the @entity2574 -49 PLA2 and both had little direct hemolytic activity. In contrast, both enzymes were approximately equipotent on the phrenic nerve-diaphragm preparation and on the isolated ventricle strip of the heart. On the @entity299 , the effects of the @entity2574 -49 PLA2 were accompanied by hydrolysis of @entity2434 and @entity3633 , whereas no phospholipid hydrolysis was observed with the Lys-49 PLA2. Evaluation of the present results, along with earlier findings using @entity2574 -49 PLA2 enzymes from Naja nigricollis, Hemachatus haemachatus and @entity18115 venoms, allows us to conclude that: The A. p. piscivorus @entity2574 -49 PLA2 enzyme resembles the @entity2574 -49 enzymes from N. @entity18115 and H. haemachatus. In contrast, the A. p. piscivorus Lys-49 PLA2 has much lower enzymatic and anticoagulant activities than the @entity2574 -49 enzymes, but equal @entity1370 and junctional effects. In contrast to some previous suggestions, basic PLA2 enzymes are not necessarily more toxic than neutral or acidic enzymes. Pharmacological effects upon the heart and phrenic nerve-diaphragm preparation correlate neither with in vitro measurements of PLA2 activity nor with actual levels of phospholipid hydrolysis in the heart or diaphragm. This suggests that PLA2 enzymes exert effects independent of phospholipid hydrolysis.
