Nitrogen Metabolism in Aedes Aegypti Mosquitoes

描述(由申请人提供)：我们已经报道埃及伊蚊雌性蚊子拥有一种非凡的生物系统，能够利用这种生物体中以前未知的代谢途径，通过血液消化释放出有毒的氨。具体地说，我们发现了Ae。与所有其他已被研究的昆虫不同，埃及伊蚊可以通过与固氮植物和细菌相同的代谢途径来解毒氨。蚊子也可以像脊椎动物那样利用谷氨酰胺的氨基产生尿酸，更令人惊讶的是，蚊子通过一些鱼类和两栖动物使用的相同代谢途径将尿酸水解为尿素。由于这些多个代谢途径的协调运行防止了蚊子组织在血餐后产生致命的氨浓度，这促使我们了解这些代谢途径是如何相互联系和调节的。因此，资助申请的主要目的是阐明氮素废物的代谢规律，以及分析参与蚊子氨代谢的C和N分子的通量。这些研究将结合使用RNA干扰和质谱学技术进行。使用生物进化方法控制蚊子种群的尝试取决于对蚊子生物学和新陈代谢的透彻了解。因此，如果我们提议的实验成功进行，它们将开辟新的令人兴奋的发现，可以应用于设计和实施更好的蚊子控制策略。将实现以下具体目标：1-确定蚊子体内氮素浪费的调节机制。2-调查参与蚊子氨代谢的C和N分子的通量。根据我们的初步数据，氮废物的代谢调节在Ae中似乎受到严格的调控。埃及伊蚊。因此，我们的目标是了解这种调节机制如何控制成年雌性蚊子的氨代谢。

DESCRIPTION (provided by applicant): We have reported that Aedes aegypti female mosquitoes possess a remarkable biological system to survive toxic ammonia concentrations released by blood meal digestion using previously unknown metabolic pathways present in this organism. Specifically, we have found that Ae. aegypti can detoxify ammonia by the same metabolic pathways that nitrogen fixing plants and bacteria use, unlike all other insects that have been studied. Mosquitoes can also use the nitrogen from the amide group of glutamine to produce uric acid as vertebrates do, and more surprisingly, mosquitoes hydrolyze uric acid into urea through the same metabolic pathway that some fish and amphibians use. Since the coordinated operation of these multiple metabolic pathways prevents a lethal ammonia concentration in the mosquito tissues after a blood meal, it impels us to know how these metabolic pathways are interconnected and regulated. Therefore, the main purpose of the grant application is to elucidate the metabolic regulation of nitrogen waste, as well as to analyze the flux of C and N molecules involved in ammonia metabolism in mosquitoes. These studies will be performed using a combination of RNA interference and mass spectrometry techniques. Attempts to control mosquito populations using biorational approaches depend on a thorough understanding of mosquito biology and metabolism. So, if the experiments that we propose are conducted successfully, they will open up new and exciting discoveries that could be applied for the design and implementation of better strategies for mosquito control. The following specific aims will be pursued: 1- Identify the mechanisms involved in the regulation of nitrogen waste in mosquitoes. 2- Investigate the flux of C and N molecules involved in ammonia metabolism in mosquitoes. According to our preliminary data, the metabolic regulation of nitrogen waste appears to be tightly- regulated in Ae. aegypti mosquitoes. Therefore, our objective is to understand how this regulatory mechanism controls the ammonia metabolism in adult female mosquitoes.