Fatty Acid Catabolism & the glyoxylate shunt in Mycobact

脂肪酸分解代谢

• 批准号: 6341302
• 负责人: DAVID G RUSSELL
• 金额: $ 4.03万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341302
• 关键词: Krebs' cycle; Mycobacterium smegmatis; Mycobacterium tuberculosis; aconitate hydratase; bacteria infection mechanism; bacterial genetics; cellular pathology; cooperative study; enzyme activity; enzyme inhibitors; fatty acid metabolism; genetic library; genetic screening; laboratory mouse; latent infection; leukocyte activation /transformation; long chain fatty acid; macrophage; mutant; oxygen tension; pathologic process; short chain fatty acid

Description (adapted from the application): Isocitrate lyase (Icl) the first enzyme of the glyoxylate pathway is upregulated in M. tuberculosis when it is exposed to reduced oxygen tension or when exposed to an intracellular environment of activated macrophages. Icl competes with the Ich enzyme diverting the carbon from TCA cycle, which is otherwise wasted. The investigators suggest that Icl may utilize fatty acids found within the macrophages when they become the limiting carbon sources that explain their up-regulation and thus explain a probable mechanism by which M. tuberculosis can survive within hostile macrophages. The role of Icl in the pathogenesis of tuberculosis will be investigated under three specific aims of a funded RO1 grant addressing respectively the environmental inducers of Icl, role of Icl in maintaining latent infection and identifying inhibitors of Icl. This grant application will focus on identifying the substrates that feed the glyoxylate pathway using M. smegmatis and what this pathway does for the bacterium.

描述（根据应用程序改编）：Isocitrate裂解酶（ICL）第一个 结核分枝杆菌的乙二醇途径的酶在其上上调 暴露于减少的氧气张力或暴露于细胞内 活化巨噬细胞的环境。 ICL与ICH酶竞争 将碳从TCA循环中转移出来，否则会浪费。这 研究人员建议ICL可以利用在 巨噬细胞成为解释他们的有限碳源 上调，因此解释了结核分枝杆菌的可能机制 可以在敌对的巨噬细胞中生存。 ICL在发病机理中的作用 结核病将根据资助的RO1的三个特定目的进行研究 赠款分别针对ICL的环境诱导者，ICL的作用 保持潜在感染并识别ICL的抑制剂。这笔赠款 应用程序将重点识别供乙二醇的底物 使用Smegmatis的途径以及该途径对细菌的作用。