Comparison of enzymatic and pharmacological activities of lysine-49 and aspartate-49 phospholipases A2 from Agkistrodon piscivorus piscivorus snake venom.
Comparison of enzymatic and pharmacological activities of lysine-49 and aspartate-49 phospholipases A2 from Agkistrodon piscivorus piscivorus snake venom.
复制标题
Agkistrodon piscivorus 蛇毒赖氨酸 49 和天冬氨酸 49 磷脂酶 A2 的酶活性和药理活性比较。
DOI：
10.1016/0006-2952(87)90059-1
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发表时间：
1987
影响因子：
5.8
通讯作者：
Rosenberg,P
中科院分区：
文献类型：
--
作者：
Dhillon,DS;Condrea,E;Maraganore,JM;Heinrikson,RL;Benjamin,S;Rosenberg,P
The basic Lys-49 phospholipase A2(PLA2) fromAgkistrodon pisciuorus piscivorusvenom is homologous to the basic Asp-49 PLA2from the same venom as well as other snake venom PLA2enzymes. It differs, however, in several respects, most important being replacement of the previously invariant Asp-49 at the calcium binding site by Lys, resulting in a reversed order of addition of calcium and phospholipid, phospholipid binding first. Although the preferences for phospholipid substrates of the two enzymes are identical, the apparentVmaxof the Lys-49 PLA2was only 1.4 to 3% that of the Asp-49 enzyme. Similarly, the Lys-49 PLA2, compared to the Asp-49 PLA2had < 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 Asp-49 PLA2and 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 cardiac and neuromuscular preparations, the effects of the Asp-49 PLA2were accompanied by hydrolysis of phosphatidylcholine and phosphatidylethanolamine, whereas no phospholipid hydrolysis was observed with the Lys-49 PLA2. Evaluation of the present results, along with earlier findings using Asp-49 PLA2enzymes fromNaja nigricollis,Hemachatus haemachatusandNaja naja atravenoms, allows us to conclude that: (1) TheA. p. piscivorusAsp-49 PLA2enzyme resembles the Asp-49 enzymes fronN. n. atraandH. haemachatus. In contrast, theA. p. piscivorusLys-49 PLA2has much lower enzymatic and anticoagulant activities than the Asp-49 enzymes, but equal cardiotoxic and junctional effects. (2) In contrast to some previous suggestions, basic PLA2enzymes are not necessarily more toxic than neutral or acidic enzymes. (3) Pharmacological effects upon the heart and phrenic nerve-diaphragm preparation correlate neither within vitromeasurements of PLA2activity nor with actual levels of phospholipid hydrolysis in the heart or diaphragm. This suggests that PLA2enzymes exert effects independent of phospholipid hydrolysis.
