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 调节几种脂肪生成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着变化， 三个基本的重要状态：（a）细胞表达 分化和发育程序;（B）调节靶细胞 胰岛素、T3、肾上腺素和 胰高血糖素;和（c）在涉及饥饿期的饮食范例中 然后再喂以高碳水化合物/低脂肪饮食。 三 酶、ATP-柠檬酸裂解酶（ACL）、苹果酸酶（ME）和甘油 3-磷酸脱氢酶（GPD）已被选择用于研究。 他们是 直接饱和脂肪酸中酶的代表性实例 合成途径，一套必需的NADPH生产酶和 糖酵解和脂肪生成途径之间的酶联。 这些酶是功能上相关的有限组的成员。 中到低丰度的酶蛋白，通常（但不总是） 在许多生理变化中以协调的方式调节 上述重要国家。 目前，人们对这一现象知之甚少。 这种协调控制的分子机制。 因此，我们认为， 研究这些基因的转录和转录后调控， 基因编码区和非编码区结构的确定 ACL，ME和GPD基因的特性，并最终， 基因侧翼区域的调控序列将提供新的 哺乳动物细胞内过程的信息和见解 分化和指导靶细胞协调分化的现象 重新调整他们的酶家族水平以响应激素， 营养素 将对鼠3 T3-L1前脂肪细胞进行研究，

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