CONTROL OF LIPOGENIC ENZYMES BIOSYNTHESIS IN 3T3-L1 CELL

这项研究计划的总体目标是确定分子 调节几种产脂酶的生物合成的基础。 这些酶的数量在肝脏和脂肪细胞中发生了显著的变化。 三种基本的重要状态：(A)细胞的表达 分化和发育计划；(B)靶细胞的调节 胰岛素、三碘甲状腺原氨酸、肾上腺素和 以及(C)在涉及饥饿期的饮食模式中 然后以高碳水化合物/低脂肪饮食重新喂养。三 酶、ATP-柠檬酸裂解酶(ACL)、苹果酸酶(ME)和甘油 以3-磷酸脱氢酶(GPD)为研究对象。他们是 直接饱和脂肪酸中几种典型的酶 合成途径、一组必需的NADPH产生酶和 糖酵解途径和脂肪生成途径之间的酶连接。 这些酶是功能相关的有限组的成员 中低丰度的酶蛋白通常(但不总是) 在生理上的许多变化中以协调的方式调节 上文所述的重要状态。目前人们对此知之甚少 这种协调控制的分子机制。因此， 这些基因转录和转录后调控的研究 基因，编码区和非编码区结构的确定 对ACL、ME和GPD基因的研究，并最终确定特异性 基因两侧区域的调控序列将提供新的 关于哺乳动物细胞过程的信息和见解 分化与靶细胞协调定向现象 重置一系列酶的水平以响应荷尔蒙和 营养素。研究将在小鼠3T3-L1前脂肪细胞和

The overall goal of this research program is to determine the molecular basis for the regulation of the biosynthesis of several lipogenic enzymes. The amounts of these enzymes are markedly altered in liver and fat cells in three fundamentally important states: (a) expression of cell differentiation and developmental programs; (b) regulation of target-cell metabolism and function by the hormones insulin, T3, epinephrine and glucagon; and (c) in a dietary paradigm involving a period of starvation followed by refeeding with a high carbohydrate/low fat diet. Three enzymes, ATP-citrate lyase (ACL), malic enzyme (ME) and glycerol 3-phosphate dehydrogenase (GPD) have been chosen for study. They are representative examples of enzymes in the direct saturated fatty acid synthesis pathway, a set of essential NADPH producting enzymes and the enzymic linkage between glycolytic and lipogenic pathways, respectively. These enzymes are members of a limited group of functionally related moderate to low abundance enzyme proteins that are often (but not always) regulated in a coordinate manner in many variations of the physiologically important states described above. Little is currently known about the molecular mechanisms underlying this coordinate control. Therefore, studies on the transcriptional and post-transcriptional regulation of these genes, the determination of the structure of coding and non-coding regions of ACL, ME and GPD genes and ultimately, the characterization of specific regulatory sequences in regions flanking the genes will provide new information and insights on processes involved in mammalian cell differentiation and the phenomena which direct target cells to coordinately reset their levels of a family of enzymes in response to hormones and nutrients. Studies will be performed on murine 3T3-L1 preadipocytes and