Biochemistry Laboratory, Department of Chemistry, Universidade Federal de Lavras (UFLA), Lavras, Minas Gerais 37200-000, Brazil.
Computational Chemistry Laboratory, Department of Chemistry, Universidade Federal de Lavras (UFLA), Lavras, Minas Gerais 37200-000, Brazil.
Int J Biol Macromol. 2019 Nov 1;140:49-58. doi: 10.1016/j.ijbiomac.2019.08.125. Epub 2019 Aug 14.
Naja spp. venom is a natural source of active compounds with therapeutic application potential. Phospholipase A (PLA) is abundant in the venom of Naja spp. and can perform neurotoxicity, cytotoxicity, cardiotoxicity, and hematological disorders. The PLAs from Naja spp. venoms are Asp 49 isoenzymes with the exception of PLA Cys 49 from Naja sagittifera. When looking at the functional aspects, the neurotoxicity occurs by PLA called β-toxins that have affinity for phosphatidylcholine in nerve endings and synaptosomes membranes, and by α-toxins that block the nicotinic acetylcholine receptors in the neuromuscular junctions. In addition, these neurotoxins may inhibit K and Ca channels or even interfere with the Na/K/ATPase enzyme. The disturbance in the membrane fluidity also results in inhibition of the release of acetylcholine. The PLA can act as anticoagulants or procoagulant. The cytotoxicity exerted by PLAs result from changes in the cardiomyocyte membranes, triggering cardiac failure and hemolysis. The antibacterial activity, however, is the result of alterations that decrease the stability of the lipid bilayer. Thus, the understanding of the structural and functional aspects of PLAs can contribute to studies on the toxic and therapeutic mechanisms involved in the envenomation by Naja spp. and in the treatment of pathologies.
眼镜蛇属蛇毒是具有治疗应用潜力的活性化合物的天然来源。磷脂酶 A(PLA)在眼镜蛇属蛇毒中含量丰富,具有神经毒性、细胞毒性、心脏毒性和血液系统紊乱。除了来自尖吻蝮的 PLA Cys 49 外,眼镜蛇属蛇毒中的 PLA 都是 Asp 49 同工酶。从功能方面来看,神经毒性是由 PLA 引起的,称为β-毒素,其对神经末梢和突触体膜中的磷脂酰胆碱具有亲和力,而α-毒素则会阻断神经肌肉接头处的烟碱型乙酰胆碱受体。此外,这些神经毒素可能会抑制 K 和 Ca 通道,甚至干扰 Na/K/ATP 酶。细胞膜流动性的紊乱也会导致乙酰胆碱的释放受到抑制。PLA 可以作为抗凝剂或促凝剂。PLA 引起的细胞毒性源自心肌细胞膜的变化,引发心力衰竭和溶血。然而,抗菌活性是由于改变而降低脂双层稳定性的结果。因此,对 PLA 的结构和功能方面的理解可以促进对眼镜蛇属蛇毒中毒和治疗机制以及相关病理学的研究。