METABOLIC FLUX PATTERNS IN HEPATOMA AND HEPATOCYTES

这项建议侧重于两种制剂中的能量代谢，一种是肝癌 细胞系(HTC细胞)和分离的肝细胞制剂。这个 调查将利用方程来量化相对通量 碳通过三氯乙烷循环相关的途径。这些方程式是由下列公式导出的 发展新的三氯乙烷循环稳态模型的P.I. 碳同位素分布。这些方程的独特之处在于 它们捕捉到关于能量新陈代谢模式的信息 使用其他技术时可用。 肝细胞和肝癌细胞之间的一个关键代谢差异是 肿瘤细胞将谷氨酰胺作为一种重要的能量来源。因此， 肝癌代谢研究的主要目标是定量分析 谷氨酰胺代谢模式。在比较的模式中 在肝癌和肝细胞中的新陈代谢，由 将使用P.I.，考虑到可能存在的超过 一组特定的代谢物。 关注肝细胞代谢的研究的主要目标是改善 糖异生作用的碳同位素测量方法。私家侦探。 研究了常用修正系数的数学基础 在糖异生作用中的同位素稀释(“Hetenyi因子”) 确定它可能会对糖异生产生误导性的估计 一些例子。因此，将开发一种新的协议来估计 细胞外丙氨酸的比放射性稀释度 转化为草酰乙酸池，这是葡萄糖的前体。 这个项目的长期目标是理解量化的作用 将代谢物的流量引导到生物合成或 氧化途径并量化正常和正常之间的代谢差异 转化的细胞。

This proposal focuses on energy metabolism in two preparations, a hepatoma cell line (HTC cells), and an isolated hepatocyte preparation. The investigation will utilize equations to quantitate the relative flux of carbon through TCA cycle related pathways. These equations were derived by the P.I. in the process of developing a new steady state model of TCA cycle carbon isotope distribution. The unique feature of these equations is that they capture information about the pattern of energy metabolism not available using other techniques. A key metabolic distinction between hepatocytes and hepatoma cells is the use of glutamine as a significant energy source by tumor cells. Thus, the major goal of the hepatoma metabolic studies is a quantitative analysis of the pattern of glutamine metabolism. In comparing the pattern of metabolism in hepatoma and hepatocytes, modeling techniques developed by the P.I. will be used which consider the possible existence of more than one pool of specific metabolites. The major goal of studies focusing on hepatocyte metabolism is to improve the procedure for carbon isotopic measurement of gluconeogenesis. The P.I. has examined the mathematical basis of a commonly used correction factor for isotope dilution in gluconeogenesis ("Hetenyi's factor") and has determined that it may yield misleading estimates of gluconeogenesis in some instances. Thus, a new protocol will be developed to estimate the dilution in the specific radioactivity as extracellular alanine is converted to the oxaloacetate pool which is the precursor for glucose. The long term goals of this project are to understand the quantitative role of factors which direct the flux of metabolites into either biosynthetic or oxidative pathways and to quantify metabolic differences between normal and transformed cells.