Niederberger P, Prasad R, Miozzari G, Kacser H
Mikrobiologisches Institut, Eidgenössisch Technische Hochschule, Zürich, Switzerland.
Biochem J. 1992 Oct 15;287 ( Pt 2)(Pt 2):473-9. doi: 10.1042/bj2870473.
Decreases in enzyme activity often have little effect on the flux carried by the pathway. Similarly, up-modulation of single genes, and hence of the dependent enzyme concentrations, is frequently found to be ineffective in increasing the flux in the pathway in which the enzyme occurs. This insensitivity to enzyme variation is demonstrated experimentally for five separate enzymes in the tryptophan synthesis system of yeast, first by down-modulation of the gene dose and secondly by increasing the dose using multi-copy vectors. Such a lack of response is discussed in terms of the concepts of metabolic control analysis. When these five enzymes, however, were simultaneously increased by a multi-copy vector carrying all five genes, a substantial elevation of the flux to tryptophan was observed. These findings revealed a new phenomenon, namely the more than additive effects on the flux of simultaneous elevations of several enzyme activities.
酶活性的降低通常对该途径所承载的通量影响很小。同样，经常发现单个基因的上调以及相关酶浓度的上调，在增加含有该酶的途径中的通量方面是无效的。在酵母色氨酸合成系统中，针对五种不同的酶通过实验证明了这种对酶变化的不敏感性，首先是通过下调基因剂量，其次是使用多拷贝载体增加剂量。根据代谢控制分析的概念对这种缺乏响应的情况进行了讨论。然而，当通过携带所有五个基因的多拷贝载体同时增加这五种酶时，观察到色氨酸通量大幅升高。这些发现揭示了一种新现象，即几种酶活性同时升高对通量的影响具有超加性效应。
