METABOLIC PATHWAYS IN THE INTACT LIVER CELL

该项目是一个尝试映射主要代谢的延续 完整肝细胞中的途径，包括碳水化合物 以及脂质合成和降解。 我们将探讨定量 在添加以下物质的条件下发生的途径变化 激素如胰高血糖素、肾上腺素和胰岛素;或添加药物， 已知或疑似临床价值;或成分变化， 饮食安排。 一些14 C和氚标记的底物将 将使用，并将数据拟合以研究状态模型， 微型计算机的帮助。 我们还将尝试本地化的重要 这些途径中的控制步骤：（a）通过测量同位素通量的变化 通过酶的影响，增加或减少 总途径的速率;和（B）通过使用新的抑制剂 滴定技术 在这种方法中，在理想的（即，假设 完美的抑制剂），给定的酶受到控制，分级 失活程度，以及对总体 路径指示给定步骤是否重要（速率限制） 控制步骤。

This project is a continuation of an attempt to map major metabolic pathways in the intact liver cell, including the processes of carbohydrate and lipid synthesis and degradation. We will explore the quantitative changes in the pathways which occur under conditions of addition of hormones such as glucagon, epinephrine and insulin; or addition of drugs of known or suspected clinical value; or of changes in composition and scheduling of diet. A numer of 1 4C and tritium labelled substrates will be used, and fitting of data to study state models will be carried out with the aid of a microcomputer. We will also attempt to localize the important control steps in these pathways: (a) by measuring changes in isotopic flux through the enzymes as affected by agents which increase or decrease the rate of the overall pathways; and (b) by the use of a new inhibitor titration technique. In this approach, in the ideal (i.e., assuming a perfect inhibitor), a given enzyme is subjected to a controlled, graded extent of inactivation, and the analysis of the effect on the overall pathway indicates whether the given step is an important (rate limiting) control step.