Lipid Transport Proteins as Pharmacological Target Molecules

脂质转运蛋白作为药理学靶分子

• 批准号: 491223891
• 负责人: Professor Dr. Christoph Arenz
• 金额: --
• 依托单位: Arbeitsgruppe Organische und Bioorganische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/491223891?language=en
• 关键词: Lipid; Transport; Proteins; Pharmacological; Target

Cellular homeostasis results from the interplay of numerous regulated metabolic pathways, which may be up- or down-regulated in a pathological context. To pharmacologically influence the concentration of individual metabolites, the pacemaker enzyme (rate-limiting step) of a relevant metabolic pathway is usually inhibited. In the past, the rate-limiting enzymes of many metabolic pathways were determined from cell lysates using radiolabeled metabolites. However, topological issues were often overlooked. Biosynthesis of sphingolipids spans different compartments, requiring specific transport processes between them. Since lipids are by definition not water soluble, translocation between different membranes requires either a complex vesicular transport system or a lipid transporter in the form of a protein or enzyme. The transport processes of sphingolipid metabolites are essential components of sphingolipid biosynthesis. Recent studies show that these transport processes rather than biosynthetic enzymes determine the rate of sphingolipid biosynthesis. Therefore, transporters of sphingolipid metabolites are likely to be the more appropriate pharmacological targets.The proposed project focuses on different transport processes and their catalysts.

细胞稳态是由许多调节的代谢途径的相互作用引起的，这些途径可能在病理背景下被上调或下调。为了在药理上影响单个代谢产物的浓度，通常会抑制相关代谢途径的起搏器酶（限制步骤）。过去，使用放射性标记的代谢物从细胞裂解物中确定许多代谢途径的速率限制酶。但是，拓扑问题经常被忽略。鞘脂的生物合成跨越了不同的隔室，需要它们之间的特定运输过程。由于脂质根据定义不是水溶性，因此不同膜之间的易位需要复杂的囊泡运输系统或蛋白质或酶形式的脂质转运蛋白。鞘脂代谢物的转运过程是鞘脂生物合成的重要组成部分。最近的研究表明，这些转运过程而不是生物合成酶决定了鞘脂生物合成的速率。因此，鞘脂代谢物的转运蛋白可能是更合适的药理目标。拟议的项目侧重于不同的运输过程及其催化剂。