In the postgenomic era of biology, much attention has been given to functional genomics, or the relation between genes and higher levels of organization in the cell. The latter are typically represented as mRNA, protein, or organic metabolite complements. The theme of this review is that the operational unit of function in complex biological systems is more properly seen as the fully assembled metabolic pathway in the whole organism. Due to the connectivity, interactions, and complexity of metabolic pathways, the measurement of components is an inadequate method for predicting phenotype. Measurement of the outputs of pathways (molecular fluxes) involves different tools than static measures of components, however. Here, we review recently developed stable isotope-mass spectrometric tools for measuring fluxes through metabolic pathways in vivo, focusing on the response to dietary macronutrients (carbohydrates and fats). Methods discussed include measurement of lipid dynamics, DNA replication, hepatic assembly of lipoproteins, and long-lived protein synthesis. Measuring fluxes through multiple pathways concurrently allows regulatory themes to emerge. Use of 2H2O-labeling is emerging as a particularly powerful approach for multiple concurrent biosynthetic flux measurements. Several examples demonstrate that pathway flux results are often unexpected and not predicted by classic biochemistry or the expression of genes and proteins.

中文翻译：

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体内通过代谢途径的通量测量：功能基因组学和药物研究中的缺失环节。

在生物学的后基因组时代，功能基因组学或基因与细胞中更高水平的组织之间的关系已引起了很多关注。后者通常表示为mRNA，蛋白质或有机代谢物补体。这篇综述的主题是，复杂生物系统中的功能操作单元可以更恰当地视为整个生物体内完全组装的代谢途径。由于代谢途径的连通性，相互作用和复杂性，组分的测定是预测表型的不足方法。但是，测量路径输出（分子通量）所用的工具与静态测量组件所用的工具不同。在这里，我们回顾了最近开发的稳定同位素质谱仪，用于测量体内代谢途径的通量，着重于对饮食中大量营养素（碳水化合物和脂肪）的反应。讨论的方法包括脂质动力学的测定，DNA复制，脂蛋白的肝组装以及长寿命的蛋白质合成。同时测量通过多种途径的通量可以使监管主题浮现。2H2O标记的使用正在成为同时进行多种生物合成通量测量的一种特别强大的方法。几个例子表明，途径通量的结果通常是出乎意料的，并且不能通过经典的生物化学方法或基因和蛋白质的表达来预测。同时测量通过多种途径的通量可以使监管主题浮现。2H2O标记的使用正在成为同时进行多个生物合成通量测量的一种特别强大的方法。几个例子表明，途径通量的结果通常是出乎意料的，并且不能通过经典的生物化学方法或基因和蛋白质的表达来预测。同时测量通过多种途径的通量可以使监管主题浮现。2H2O标记的使用正在成为同时进行多个生物合成通量测量的一种特别强大的方法。几个例子表明，途径通量的结果通常是出乎意料的，并且不能通过经典的生物化学方法或基因和蛋白质的表达来预测。