Nilsson Avlant, Nielsen Jens
Chalmers University of Technology, Department of Biology and Biological Engineering, Gothenburg, SE41296, Sweden.
Technical University of Denmark, Novo Nordisk Foundation Center for Biosustainability, Hørsholm, DK2970, Denmark.
Sci Rep. 2016 Mar 1;6:22264. doi: 10.1038/srep22264.
Intermediary metabolism provides living cells with free energy and precursor metabolites required for synthesizing proteins, lipids, RNA and other cellular constituents, and it is highly conserved among living species. Only a fraction of cellular protein can, however, be allocated to enzymes of intermediary metabolism and consequently metabolic trade-offs may take place. One such trade-off, aerobic fermentation, occurs in both yeast (the Crabtree effect) and cancer cells (the Warburg effect) and has been a scientific challenge for decades. Here we show, using flux balance analysis combined with in vitro measured enzyme specific activities, that fermentation is more catalytically efficient than respiration, i.e. it produces more ATP per protein mass. And that the switch to fermentation at high growth rates therefore is a consequence of a high ATP production rate, provided by a limited pool of enzymes. The catalytic efficiency is also higher for cells grown on glucose compared to galactose and ethanol, which may explain the observed differences in their growth rates. The enzyme F1F0-ATP synthase (Complex V) was found to have flux control over respiration in the model, and since it is evolutionary conserved, we expect the trade-off to occur in organisms from all kingdoms of life.
中间代谢为活细胞提供合成蛋白质、脂质、RNA和其他细胞成分所需的自由能和前体代谢物，并且在生物物种中高度保守。然而，细胞中只有一小部分蛋白质可用于中间代谢的酶，因此可能会发生代谢权衡。其中一种权衡，即有氧发酵，在酵母（克奈特效应）和癌细胞（瓦伯格效应）中均会发生，并且几十年来一直是一个科学挑战。在这里，我们结合体外测量的酶比活性，使用通量平衡分析表明，发酵比呼吸作用具有更高的催化效率，即每单位蛋白质质量产生更多的ATP。因此，在高生长速率下转向发酵是由有限的酶库提供的高ATP产生速率的结果。与半乳糖和乙醇相比，在葡萄糖上生长的细胞的催化效率也更高，这可能解释了观察到的它们生长速率的差异。在该模型中发现F1F0-ATP合酶（复合体V）对呼吸作用具有通量控制，并且由于它在进化上是保守的，我们预计这种权衡会在所有生命王国的生物体中发生。
