Daran-Lapujade Pascale, Rossell Sergio, van Gulik Walter M, Luttik Marijke A H, de Groot Marco J L, Slijper Monique, Heck Albert J R, Daran Jean-Marc, de Winde Johannes H, Westerhoff Hans V, Pronk Jack T, Bakker Barbara M
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC, Delft, The Netherlands.
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15753-8. doi: 10.1073/pnas.0707476104. Epub 2007 Sep 26.
Metabolic fluxes may be regulated "hierarchically," e.g., by changes of gene expression that adjust enzyme capacities (V(max)) and/or "metabolically" by interactions of enzymes with substrates, products, or allosteric effectors. In the present study, a method is developed to dissect the hierarchical regulation into contributions by transcription, translation, protein degradation, and posttranslational modification. The method was applied to the regulation of fluxes through individual glycolytic enzymes when the yeast Saccharomyces cerevisiae was confronted with the absence of oxygen and the presence of benzoic acid depleting its ATP. Metabolic regulation largely contributed to the approximately 10-fold change in flux through the glycolytic enzymes. This contribution varied from 50 to 80%, depending on the glycolytic step and the cultivation condition tested. Within the 50-20% hierarchical regulation of fluxes, transcription played a minor role, whereas regulation of protein synthesis or degradation was the most important. These also contributed to 75-100% of the regulation of protein levels.
代谢通量可以通过“分级”调节，例如，通过改变基因表达来调整酶的活性（V(max)），和/或通过酶与底物、产物或别构效应物的相互作用进行“代谢”调节。在本研究中，开发了一种方法，将分级调节剖析为转录、翻译、蛋白质降解和翻译后修饰的贡献。当酿酒酵母面临缺氧和苯甲酸消耗其ATP的情况时，该方法被应用于分析通过各个糖酵解酶的通量调节。代谢调节在很大程度上导致了通过糖酵解酶的通量发生约10倍的变化。这一贡献在50%到80%之间变化，具体取决于所测试的糖酵解步骤和培养条件。在通量的50% - 20%的分级调节中，转录起的作用较小，而蛋白质合成或降解的调节最为重要。这些因素也对蛋白质水平调节的75% - 100%有贡献。
