The role of stoichiometric analysis in studies of metabolism: An example
The role of stoichiometric analysis in studies of metabolism: An example
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DOI：
10.1006/jtbi.2002.2547
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发表时间：
2002-05-21
影响因子：
2
通讯作者：
Hofmeyr, JHS
中科院分区：
文献类型：
--
作者：
Cornish-Bowden, A;Hofmeyr, JHS
化学计量分析使用矩阵代数来推断代谢网络中隐含的约束。当应用于简单的网络时，它通常会给人一种不必要的复杂的印象，即通过检查获得显而易见的信息，例如，腺嘌呤核苷酸的浓度总和是恒定的。应用于一个更复杂的例子，即布鲁氏锥虫的糖酵解，它得到的信息远不明显，可能对开发消除这种寄生虫的治疗方法具有重要意义。即使在简化形式下，该网络也包含涉及11种代谢物的9个反应或运输步骤。这立即表明，必须至少有两个化学计量限制，而且确实有两个可以通过检查来识别：腺嘌呤核苷酸的守恒和NAD的两种形式的守恒。然而，还有第三种，它涉及八种不同的磷酸化中间体，其组合不明显，很难通过检查识别。通过检验也很难认识到不存在第四个化学计量约束。高斯消去法提供了一种系统的方法来分析一个网络，使其包含的所有化学计量关系自动出现。(C) 2002 Elsevier Science Ltd.版权所有。
Stoichiometric analysis uses matrix algebra to deduce the constraints implicit in metabolic networks. When applied to simple networks, it can often give the impression of being an unnecessarily complicated way of arriving at information that is obvious from inspection, for example, that the sum of the concentrations of the adenine nucleotides is constant. Applied to a more complicated example, that of glycolysis in Trypanosoma brucei, it yields information that is far from obvious and may have importance for developing therapeutic ways of eliminating this parasite. Even in simplified form, the network contains nine reactions or transport steps involving 11 metabolites. This immediately shows that there must be at least two stoichiometric constraints, and indeed two can be recognized by inspection: conservation of adenine nucleotides and conservation of the two forms of NAD. There is, however, a third, which involves eight different phosphorylated intermediates in non-obvious combinations and is very difficult to recognize by inspection. It is also difficult to recognize by inspection that no fourth stoichiometric constraint exists. Gaussian elimination provides a systematic way of analysing a network in such a way that all the stoichiometric relationships that it contains emerge automatically. (C) 2002 Elsevier Science Ltd. All rights reserved.