Metabolite transporter and metabolic energy balance - from whole organism to sub-cellular regulation in fish

代谢转运蛋白和代谢能量平衡 - 从整个生物体到鱼类的亚细胞调节

• 批准号: 238390-2006
• 负责人: Wang, Yuxiang
• 金额: $ 2.14万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363727
• 关键词: Metabolite; transporter; metabolic; energy; balance

Organisms strive to maintain a delicate energy balance in a changing environment. In higher organism, such as vertebrates, the coordination of the various physiological functions over the course of evolution has been partially achieved through the compartmentalization of metabolic processes. An efficient energy transport system becomes vital for metabolite distribution among various tissues, cells, and sub-cellular organelles to maintain an energy balance. We use fish as a model to profile the metabolic links between the precise regulatory mechanism of the metabolite transport system and the preference of fuel utilization. Glycolysis is a metabolic energy production pathway that is present in all organisms, which relies on glucose as a substrate. Under normal physiological states, glucose is shuttled throughout the body and completely used for energy production in most tissues. It has been assumed that under O2 limited situations, glucose oxidation is short-circuited and lactate is formed in an attempt to maintain energy balance. However, currently, lactate and other monocarboxylate (MC) are considered to be important metabolic intermediate substrates for inter- and intra-cellular fuel shuttling. In fish, MC and glucose metabolism and transport are handled differently compared to mammals. Some fish species are glucose insensitive (i.e. similar to a diabetic state) while others may rely mainly on MC as alternative fuel supply. We will investigate if the reliance on MC and its associated transport system afford fish a greater metabolic flexibility than observed in other vertebrates. We take a comparative approach to identify the genes of monocarboxylate transporters in bonyfish, elasmobranches and cyclostomata each of which possess different anaerobic capabilities, fuel preference and hypoxia tolerance. We will examine the regulatory mechanism of the transport system from the molecular to the physiological level under O2-limiting or other energy demanding processes. The knowledge obtained will allow researchers and students to gain insight into the evolution and biodiversity of energy metabolism, and shed light on many issues such as optimal fuel utilization and growth in fish, and diabetics and hypoxia tolerance in the biomedical area.

生物体努力在不断变化的环境中保持微妙的能量平衡。在高等生物中，如脊椎动物，在进化过程中各种生理功能的协调部分是通过代谢过程的区室化来实现的。有效的能量转运系统对于代谢物在各种组织、细胞和亚细胞器之间的分布以维持能量平衡变得至关重要。我们使用鱼作为模型来描绘代谢物运输系统的精确调节机制和燃料利用的偏好之间的代谢联系。糖酵解是存在于所有生物体中的代谢能量产生途径，其依赖于葡萄糖作为底物。在正常的生理状态下，葡萄糖穿梭于整个身体，并完全用于大多数组织的能量生产。据推测，在氧气有限的情况下，葡萄糖氧化被短路，乳酸盐形成，试图保持能量平衡。然而，目前，乳酸盐和其他单羧酸盐（MC）被认为是细胞内和细胞间燃料穿梭的重要代谢中间底物。在鱼类中，MC和葡萄糖代谢和运输的处理方式与哺乳动物不同。一些鱼类对葡萄糖不敏感（即类似于糖尿病状态），而其他鱼类可能主要依赖MC作为替代燃料供应。我们将调查，如果依赖MC及其相关的运输系统提供鱼类更大的代谢灵活性比其他脊椎动物。我们采取比较的方法来确定的单羧酸转运蛋白的基因在小骨鱼，板鳃类和圆口门，其中每一个具有不同的厌氧能力，燃料偏好和缺氧耐受性。我们将研究从分子到生理水平的运输系统下O2限制或其他能源需求的过程中的监管机制。所获得的知识将使研究人员和学生能够深入了解能量代谢的进化和生物多样性，并阐明许多问题，如鱼类的最佳燃料利用和生长，以及生物医学领域的糖尿病和缺氧耐受性。