Mobilization of Triacylglycerol Stores in Insects

昆虫体内三酰甘油储存的动员

• 批准号: 6620747
• 负责人: Estela L. Arrese
• 金额: $ 18.61万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620747
• 关键词: Manduca; age difference; arthropod genetics; chemical kinetics; chemical structure function; diacylglycerols; enzyme model; enzyme substrate complex; hormone regulation /control mechanism; intermolecular interaction; intracellular transport; invertebrate hormone; larva; lipid metabolism; lipid transport; macromolecule; mature animal; model design /development; molecular cloning; protein kinase A; protein purification; radiotracer; stereochemistry; transport proteins; triacylglycerol lipase; triglycerides

DESCRIPTION: (provided by the applicant): Unlike vertebrates, where the stored fatty acids are mobilized as free fatty acids, a great number of insects, mobilizes fatty acids as an-1, 2-diacylglycerol (DG). The mobilization of TG stores requires the action of a TG-lipase, whose activity is hormonally regulated. The substrate of the lipase (TG) is found in large intracellular lipid droplets, which are constituted by a core of TG surrounded by a complex surface layer of phospholipids and proteins. On the other hand, the TG-lipase localizes in the cytosol of lipolytically unstimulated fat body cells. Lipolysis involves the interaction of the lipase with the surface of the lipid droplet. It is known that activation of lipolysis promotes both an increase of intracellular calcium concentration and activation of amp-dependent protein kinase (A-kinase) but the basic mechanisms involved in how phosphorylation-dephosphorylation reactions modulate the rate of lipolysis is unknown. Moreover, little is known about the relevance and nature of the structural and compositional changes that affect the lipid droplet when lipolysis is hormonally activated. These changes must ultimately affect the interaction of the lipase with the lipid substrate and the concomitant activation of lipolysis. DG moves from the lipid droplet to the plasma membrane by an uncharacterized mechanism. It appears that after the conversion of TG into DG on the surface of the lipid droplets, DG would be transferred to a cytosolic carrier, which in turn would target the delivery of DG across the plasma membrane. The overall goals of this project are to establish the mechanisms regulating lipolysis by determining the factors that promotes the interaction between TG-lipase and its substrate, the lipid droplet and to define the mechanism of intracellular transport of DG. Clearly the elucidation of these mechanisms is of fundamental importance in insect biochemistry and physiology. These studies will provide comprehensive information on the lipolytic process in insects and this knowledge could also contribute to the broad field of lipid metabolism and transport in vertebrates.

描述：（由申请人提供）：与脊椎动物不同，储存的 脂肪酸以游离脂肪酸的形式被动员，大量的昆虫， 以 an-1, 2-二酰基甘油 (DG) 的形式动员脂肪酸。 TG的动员 储存需要 TG 脂肪酶的作用，其活性与激素有关 受监管。脂肪酶 (TG) 的底物存在于大细胞内 脂滴，由 TG 核心构成，周围被复合物包围 表层为磷脂和蛋白质。另一方面，TG-脂肪酶 定位于未受脂解刺激的脂肪体细胞的细胞质中。 脂肪分解涉及脂肪酶与脂质表面的相互作用 水滴。众所周知，脂肪分解的激活会促进 细胞内钙浓度和amp依赖性蛋白的激活 激酶（A-激酶），但参与的基本机制 磷酸化-去磷酸化反应调节脂解速率 未知。此外，人们对这一事件的相关性和性质知之甚少。 影响脂滴的结构和成分变化 脂肪分解是由激素激活的。这些变化最终必定会影响 脂肪酶与脂质底物以及伴随物的相互作用 脂肪分解的激活。 DG 从脂滴移动到质膜 通过一种未知的机制。看来TG转换后 进入脂滴表面的 DG，DG 将被转移到 胞质载体，反过来将 DG 靶向递送至整个细胞 质膜。该项目的总体目标是建立 通过确定促进脂肪分解的因素来调节脂肪分解的机制 TG-脂肪酶与其底物脂滴之间的相互作用 定义 DG 的细胞内转运机制。解释清楚 这些机制对于昆虫生物化学至关重要 生理。这些研究将提供有关 昆虫的脂肪分解过程，这一知识也可能有助于 脊椎动物脂质代谢和运输的广泛领域。