Carlini Celia R, Ligabue-Braun Rodrigo
Brain Institute (Instituto do Cérebro-INSCER), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil; Center of Biotechnology, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
Center of Biotechnology, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
Toxicon. 2016 Feb;110:90-109. doi: 10.1016/j.toxicon.2015.11.020. Epub 2015 Dec 12.
Ureases are metalloenzymes that hydrolyze urea into ammonia and carbon dioxide. They were the first enzymes to be crystallized and, with them, the notion that enzymes are proteins became accepted. Novel toxic properties of ureases that are independent of their enzyme activity have been discovered in the last three decades. Since our first description of the neurotoxic properties of canatoxin, an isoform of the jack bean urease, which appeared in Toxicon in 1981, about one hundred articles have been published on "new" properties of plant and microbial ureases. Here we review the present knowledge on the non-enzymatic properties of ureases. Plant ureases and microbial ureases are fungitoxic to filamentous fungi and yeasts by a mechanism involving fungal membrane permeabilization. Plant and at least some bacterial ureases have potent insecticidal effects. This entomotoxicity relies partly on an internal peptide released upon proteolysis of ingested urease by insect digestive enzymes. The intact protein and its derived peptide(s) are neurotoxic to insects and affect a number of other physiological functions, such as diuresis, muscle contraction and immunity. In mammal models some ureases are acutely neurotoxic upon injection, at least partially by enzyme-independent effects. For a long time bacterial ureases have been recognized as important virulence factors of diseases by urease-producing microorganisms. Ureases activate exocytosis in different mammalian cells recruiting eicosanoids and Ca(2+)-dependent pathways, even when their ureolytic activity is blocked by an irreversible inhibitor. Ureases are chemotactic factors recognized by neutrophils (and some bacteria), activating them and also platelets into a pro-inflammatory "status". Secretion-induction by ureases may play a role in fungal and bacterial diseases in humans and other animals. The now recognized "moonlighting" properties of these proteins have renewed interest in ureases for their biotechnological potential to improve plant defense against pests and as potential targets to ameliorate diseases due to pathogenic urease-producing microorganisms.
脲酶是一种金属酶，可将尿素水解为氨和二氧化碳。它们是最早被结晶的酶，随着它们的出现，酶是蛋白质的观点也被人们所接受。在过去三十年中，人们发现了脲酶具有与酶活性无关的新毒性特性。自1981年我们首次在《毒素学》杂志上描述刀豆脲酶的一种同工型——刀豆毒素的神经毒性特性以来，已经发表了约一百篇关于植物和微生物脲酶“新”特性的文章。在此，我们综述了目前关于脲酶非酶特性的知识。植物脲酶和微生物脲酶对丝状真菌和酵母具有杀真菌毒性，其作用机制涉及真菌细胞膜的通透性改变。植物和至少一些细菌脲酶具有强大的杀虫作用。这种昆虫毒性部分依赖于昆虫消化酶对摄入的脲酶进行蛋白水解后释放出的一种内部肽。完整的蛋白质及其衍生肽对昆虫具有神经毒性，并影响许多其他生理功能，如利尿、肌肉收缩和免疫。在哺乳动物模型中，一些脲酶注射后具有急性神经毒性，至少部分是通过与酶无关的效应。长期以来，细菌脲酶一直被认为是产脲酶微生物引起疾病的重要毒力因子。即使脲酶的尿素分解活性被不可逆抑制剂阻断，脲酶仍能激活不同哺乳动物细胞中的胞吐作用，募集类花生酸和钙依赖途径。脲酶是被中性粒细胞（以及一些细菌）识别的趋化因子，可激活它们，还能使血小板进入促炎“状态”。脲酶诱导分泌可能在人类和其他动物的真菌和细菌疾病中起作用。这些蛋白质目前被认可的“兼职”特性，因其在改善植物对害虫防御方面的生物技术潜力以及作为改善由产脲酶致病微生物引起疾病的潜在靶点，而重新引发了人们对脲酶的兴趣。
