Nutrient sensing and hexokinases in T. brucei

T. brucei 中的营养感应和己糖激酶

• 批准号: 7911534
• 负责人: JAMES Culvin MORRIS
• 金额: $ 1.14万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911534
• 关键词: African Trypanosomiasis; Amino Acids; Anabolism; Biochemical; Biology; Blood Circulation; Cell physiology; Cells; Complex; Cues; Development; Enzymes; Exhibits; Figs - dietary; Fostering; Fumaric acid; Glucose; Glycolysis; Goals; Hexoses; In Vitro; Mammals; Mediator of activation protein; Messenger RNA; Metabolic; Metabolic Pathway; Metabolism; Molecular; Myristic Acids; Nutrient; Parasites; Pathway interactions; Phosphorylation Inhibition; Play; Production; Proteins; Publishing; Regulation; Research; Role; Staging; Surface; Trypanosoma brucei brucei; Tsetse Flies; Work; base; detection of nutrient; environmental change; enzyme mechanism; fatty acid biosynthesis; glucose metabolism; graduate student; hexokinase; in vitro activity; innovation; new therapeutic target; novel strategies; planetary Atmosphere; public health relevance; response; sugar; therapeutic development; vector

DESCRIPTION (provided by applicant): The sugar glucose is essential to the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. Heretofore, we have known very little about the regulation of a key enzyme in glucose metabolism, hexokinase (TbHK1). Recently, our group has identified a second HK (TbHK2) that regulates the first. This observation, along with our finding that products from other cellular processes can alter HK activity, suggest that HK serves as a central mediator of metabolism in the cell. Here, we propose to explore how TbHK2 regulates TbHK1 at both the mRNA and protein levels. Further, we will consider how the enzyme is regulated by other mechanisms, including phosphorylation and inhibition by other cellular metbolites. Our long-term goal is to carefully characterize the roles of the two HKs in the biology of T. brucei, with a particular emphasis on understanding the role of these proteins in regulation of metabolism. We hypothesize that the proteins may regulate the cells' response to environmental changes in nutrient availability that occurs as the parasites move from one host to another. PUBLIC HEALTH RELEVANCE: Trypanosoma brucei, the causative agent of African sleeping sickness, infects an estimated 500,000 people annually and is fatal if untreated. The research proposed here will further our understanding of the regulation of a metabolic pathway that is essential to the parasite suggesting that we may identify novel therapeutic targets.

描述（由申请人提供）：糖葡萄糖对非洲眠病的致病药物Brucei原生动物寄生虫锥虫瘤至关重要。迄今为止，我们对葡萄糖代谢，己糖酶（TBHK1）中关键酶的调节几乎不知道。最近，我们的小组确定了一个调节第一个的HK（TBHK2）。这一观察结果以及我们发现来自其他细胞过程的产品可以改变HK活性，这表明HK是细胞中代谢的中心介体。在这里，我们建议探索TBHK2如何调节mRNA和蛋白质水平的TBHK1。此外，我们将考虑如何通过其他机制调节该酶，包括其他细胞杀菌岩的磷酸化和抑制。我们的长期目标是仔细地表征两个香港在布鲁氏菌生物学中的作用，并特别强调理解这些蛋白质在调节代谢中的作用。我们假设蛋白质可以调节细胞对养分从一个宿主转移到另一个宿主的养分可用性变化的反应。 公共卫生相关性：非洲睡病的病因锥虫锥虫锥虫瘤，每年感染大约50万人，如果没有治疗，则致命。这里提出的研究将进一步了解我们对寄生虫必不可少的代谢途径的调节，这表明我们可以识别新的治疗靶标。