Department of Bioinformatics, School of Biology and Pharmaceutics and JenAge Research Core, Friedrich Schiller University of Jena, Germany.
FEBS J. 2012 Sep;279(17):3192-202. doi: 10.1111/j.1742-4658.2012.08700.x. Epub 2012 Aug 17.
Substrate cycles, also known as futile cycles, are cyclic metabolic routes that dissipate energy by hydrolysing cofactors such as ATP. They were first described to occur in the muscles of bumblebees and brown adipose tissue in the 1970s. A popular example is the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate and back. In the present study, we analyze a large number of substrate cycles in human metabolism that consume ATP and discuss their statistics. For this purpose, we use two recently published methods (i.e. EFMEvolver and the K-shortest EFM method) to calculate samples of 100,000 and 15,000 substrate cycles, respectively. We find an unexpectedly high number of substrate cycles in human metabolism, with up to 100 reactions per cycle, utilizing reactions from up to six different compartments. An analysis of tissue-specific models of liver and brain metabolism shows that there is selective pressure that acts against the uncontrolled dissipation of energy by avoiding the coexpression of enzymes belonging to the same substrate cycle. This selective force is particularly strong against futile cycles that have a high flux as a result of thermodynamic principles.
基质循环，也称为无效循环，是通过水解辅助因子（如 ATP）来消耗能量的循环代谢途径。它们最初是在 20 世纪 70 年代在大黄蜂的肌肉和棕色脂肪组织中被描述的。一个流行的例子是果糖 6-磷酸转化为果糖 1,6-二磷酸并返回。在本研究中，我们分析了人体代谢中大量消耗 ATP 的基质循环，并讨论了它们的统计学特性。为此，我们使用了两种最近发表的方法（即 EFMEvolver 和 K-最短 EFM 方法），分别计算了 100,000 和 15,000 个基质循环的样本。我们发现人体代谢中存在着数量惊人的基质循环，每个循环最多有 100 个反应，利用来自多达六个不同隔室的反应。对肝脏和大脑代谢的组织特异性模型的分析表明，存在一种选择性压力，通过避免表达属于同一基质循环的酶，来防止能量的失控消耗。这种选择压力在由于热力学原理而具有高通量的无效循环中尤为强烈。
