The Peculiar Glycolytic Pathway in Hyperthermophylic Archaea: Understanding Its Whims by Experimentation In Silico.
The Peculiar Glycolytic Pathway in Hyperthermophylic Archaea: Understanding Its Whims by Experimentation In Silico.
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DOI：
10.3390/ijms18040876
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发表时间：
2017-04-20
影响因子：
5.6
通讯作者：
Westerhoff HV
中科院分区：
文献类型：
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作者：
Zhang Y;Kouril T;Snoep JL;Siebers B;Barberis M;Westerhoff HV
数学模型是系统生物学的关键，它们通常描述生物网络的拓扑结构和动力学，列出生化实体及其彼此之间的关系。一些（超）嗜热古菌含有一种酶，称为非磷酸化甘油醛-3-磷酸脱氢酶（GAPN），它催化甘油醛-3-磷酸直接氧化为3-磷酸甘油酸，通过磷酸甘油酸激酶进行底物水平磷酸化，从而省略腺苷5 ' -三磷酸（ATP）的形成。在本研究中，我们提出了三个假设，可以从功能上解释为什么GAPN存在于这些古菌中，然后构建和使用数学模型来验证这三个假设。本研究采用了嗜热酸性古菌Sulfolobus solfataricus （S. solfataricus）酶的动力学参数，该古菌在60 ~ 90°C和pH 2 ~ 4之间生长最佳。为了进行比较，我们使用了酿酒酵母（S. cerevisiae）的模型，这是一种可以在中等温度下生活的生物。我们发现第一个假设，即甘油醛-3-磷酸脱氢酶（GAPDH）加磷酸甘油酸激酶（PGK）途径（GAPN的替代途径）在热力学上过于上坡，而第三个假设，即GAPDH加PGK需要在糖异生方向上携带通量，这两个假设都是正确的。第二种假设，即GAPDH + PGK途径比GAPN途径所传递的每丙酮酸1个ATP要少，只有在GAPDH反应速率高且1,3-二磷酸甘油酸（BPG）以高速率自发降解为3PG时才正确。
Mathematical models are key to systems biology where they typically describe the topology and dynamics of biological networks, listing biochemical entities and their relationships with one another. Some (hyper)thermophilic Archaea contain an enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate omitting adenosine 5′-triphosphate (ATP) formation by substrate-level-phosphorylation via phosphoglycerate kinase. In this study we formulate three hypotheses that could explain functionally why GAPN exists in these Archaea, and then construct and use mathematical models to test these three hypotheses. We used kinetic parameters of enzymes of Sulfolobus solfataricus (S. solfataricus) which is a thermo-acidophilic archaeon that grows optimally between 60 and 90 °C and between pH 2 and 4. For comparison, we used a model of Saccharomyces cerevisiae (S. cerevisiae), an organism that can live at moderate temperatures. We find that both the first hypothesis, i.e., that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plus phosphoglycerate kinase (PGK) route (the alternative to GAPN) is thermodynamically too much uphill and the third hypothesis, i.e., that GAPDH plus PGK are required to carry the flux in the gluconeogenic direction, are correct. The second hypothesis, i.e., that the GAPDH plus PGK route delivers less than the 1 ATP per pyruvate that is delivered by the GAPN route, is only correct when GAPDH reaction has a high rate and 1,3-bis-phosphoglycerate (BPG) spontaneously degrades to 3PG at a high rate.