Glycolysis: thermodynamics and pathway predictions

糖酵解：热力学和途径预测

基本信息

批准号：
316870850
负责人：
Privatdozent Dr.-Ing. Christoph Held
金额：
--
依托单位：
Lehrstuhl für Allgemeine Physikalische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316870850?language=en
关键词：
Glycolysis thermodynamics pathway predictions

项目摘要

The application of thermodynamics with published models still does not allow satisfactory predictions of the feasibility of biochemical pathways. This is due to the fact that basic data are either not published in the literature so far or available data is very inaccurate (group contribution methods). These basic data include thermodynamic data for pure metabolites as well as data on reaction equilibria. The latter depend on a number of parameters (e.g., pH, temperature, composition of the reaction medium in the cytoplasm). These data are included in rigorous models that depict metabolic pathways mathematically. To make these models more predictive, accurate thermodynamic data on pure metabolites as well as on reaction equilibria must be available. Further, effects like molecular crowding must be considered to make metabolic networks better predictable. If such data were available, they would be applicable in mathematical models for the description of metabolic networks, similar to it what has already been reached for systems of comparable complexity (e.g., petroleum refineries).This project aims to use new thermodynamic tools for the quantitative determination of properties of pure metabolites and reaction equilibria in order to predict the thermodynamics of the metabolic pathways. Glycolysis is chosen for that purpose as especially thermodynamics of glycolysis is still not understood. In this proposal, in vitro studies are suggested that address complex interactions that are typical for living systems (presence of salts and molecular crowders). This will allow investigating their influence on the thermodynamics of metabolic reactions, a question that is strongly discussed in the community.In a first step, new basic data for selected metabolites and individual reactions within glycolysis will be determined. The influence of real conditions in the cytoplasm on these data will be investigated e.g., pH or composition of the cytoplasm. In a second step, the effects of bio-typical phenomena (species diversity, crowding) on thermodynamics and mass-flow calculations will be examined. This will finally show how consistent thermodynamic data can improve the predictive power of metabolic network calculations.To achieve the goal, thermochemistry, quantum chemistry and thermodynamics have to be combined with material flow analysis:- Verevkin: Determination and prediction of basic data of the pure metabolites- Held: Determination and prediction of the reaction equilibria of the individual reaction steps and under the influence of real cell conditions- Maskow: application of these data in simplified and real metabolic networks under non-equilibrium conditionsThe project results obtained will be applied in biotechnology (bioengineering, systems biology).

热力学与已发表模型的应用仍然无法满足生化途径的可行性的满意预测。这是由于以下事实：到目前为止，基本数据尚未在文献中发布，或者可用的数据非常不准确（小组贡献方法）。这些基本数据包括纯代谢产物的热力学数据以及反应平衡的数据。后者取决于许多参数（例如pH，温度，细胞质中反应培养基的组成）。这些数据包含在数学描述代谢途径的严格模型中。为了使这些模型更具预测性，必须提供有关纯代谢产物以及反应平衡的准确热力学数据。此外，必须考虑诸如分子拥挤之类的效果，以使代谢网络更好地预测。如果有可用的数据，它们将适用于数学模型，用于描述代谢网络，类似于与可比复杂性系统（例如，石油炼油厂）所达到的目标。该项目旨在使用新的热力学工具来定量地确定纯代谢物和反应在纯净的途径中，以预测热力学的效果。为此目的选择了糖酵解，因为尤其是糖酵解的热动力学仍然尚不清楚。在此提案中，建议在体外研究中解决生活系统（存在盐和分子拥挤者）典型的复杂相互作用。这将允许研究他们对代谢反应的热力学的影响，这个问题在社区中得到了强烈讨论。在第一步中，将确定所选代谢物的新基本数据，并确定糖酵解中的个体反应。细胞质中实际条件对这些数据的影响将研究例如细胞质的pH或组成。第二步，将研究生物典型现象（物种多样性，拥挤）对热力学和质量流计算的影响。这将最终表明如何一致的热力学数据如何改善代谢网络计算的预测能力。要实现目标，热化学，量子化学和热力学必须与材料流量分析相结合： - verevkin：纯代谢物的基本数据的确定和预测纯代谢物的基本数据 - 持有的纯粹的影响和预测的实际影响和实际影响的情况：这些效果的确定和预测：这些实际影响的情况：这些影响力的实际影响：这些影响的效果：这些掩护的影响：这些影响：这些个上的反应 - 施加了这些影响：这些影响：这些影响：这些影响：这些影响：这些影响的情况下：这些影响：这些影响：这些影响：这些影响：这些影响：这些影响：这些影响：这些影响的效果：在非平衡条件下的代谢网络将应用于生物技术（生物工程，系统生物学）。